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Compuestos de vitamina D para pacientes con nefropatías crónicas que requieren diálisis

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Referencias

Referencias de los estudios incluidos en esta revisión

Ir a:

Akiba 1998 {published data only}

Akiba T, Marumo F, Owada A, Kurihara S, Inoue A, Chida Y, et al. Controlled trial of falecalcitriol versus alfacalcidol in suppression of parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism. American Journal of Kidney Diseases 1998;32(2):238‐46. [MEDLINE: 9708607]
Akiba T, Tamura H, Hata T, Kurihara S, Ando R, Chida C, et al. Falecalcitriol (FC), but not alfacalcidol (AC), suppresses secondary hyperparathyroidism in hemodialysis (HD) patients (Pts) ‐ a well‐controlled crossover study [abstract]. Nephrology 1997;3(Suppl 1):S303. [CENTRAL: CN‐00460259]

Akizawa 2004 {published data only}

Akizawa T, Kurokawa M, Suzuki M, Akiba T, Nishizawa Y, Ohashi Y, et al. Suppressive effect of 22‐oxacalcitriol (OCT) on secondary hyperparathyroidism (2 HPT) of hemodialysis (HD) patients. A double‐blind comparison among four doses [abstract]. Journal of the American Society of Nephrology 1996;7(9):1810. [CENTRAL: CN‐00444128]
Akizawa T, Ohashi Y, Akiba T, Suzuki M, Nishizawa Y, Ogata E, et al. Dose‐response study of 22‐oxacalcitriol in patients with secondary hyperparathyroidism. Therapeutic Apheresis & Dialysis 2004;8(6):480‐91. [MEDLINE: 15663548]

Bacchini 1997 {published data only}

Bacchini G, Fabrizi F, Pontoriero G, Marcelli D, Di Filippo S, Locatelli F. 'Pulse oral' versus intravenous calcitriol therapy in chronic hemodialysis patients. A prospective and randomized study. [erratum appears in Nephron 1998 Aug;79(4):509]. Nephron 1997;77(3):267‐72. [MEDLINE: 9375818]

Baker 1986 {published data only}

Baker LR, Muir JW, Sharman VL, Abrams SM, Greenwood RN, Cattell WR, et al. Controlled trial of calcitriol in hemodialysis patients. Clinical Nephrology 1986;26(4):185‐191. [MEDLINE: 3536232]

Berl 1980 {published data only}

Berl T, Berns AS, Hufer WE, Hammill K, Alfrey AC, Arnaud CD, et al. 1,25 dihydroxycholecalciferol effects in chronic dialysis. A double‐blind controlled study. Annals of Internal Medicine 1978;88(6):774‐80. [MEDLINE: 208439]
Berl T, Berns AS, Huffer WE, Alfrey AC, Arnaud CD, Schrier RR. Controlled trial of the effects of 1,25‐dihydroxycholecalciferol in patients treated with regular dialysis. Contributions to Nephrology 1980;18:72‐81. [MEDLINE: 6243528]

Borazan 2003 {published data only}

Borazan A, Ustun H, Cefle A, Sekitmez N, Yilmaz A. Comparative efficacy of oral and intravenous calcitriol treatment in haemodialysis patients: effects on serum biochemistry and cytokine levels. Journal of International Medical Research 2003;31(6):489‐96. [MEDLINE: 14708413]

Buccianti 1981 {published data only}

Buccianti G, Valenti G, Miradoli R. Treatment of uremic osteodystrophy. A clinical trial with calcitonin, 25‐hydroxycholecalciferol and 1,25‐dihydroxycholecalciferol. Dialysis and Transplantation 1981;10(6):523‐28. [EMBASE: 1981144740]

Caravaca 1995 {published data only}

Caravaca F, Cubero JJ, Jimenez F, Lopez JM, Aparicio A, Cid MC, et al. Effect of the mode of calcitriol administration on PTH‐ionized calcium relationship in uraemic patients with secondary hyperparathyroidism. Nephrology Dialysis Transplantation 1995;10(5):665‐70. [MEDLINE: 7566580]

Coen 1982 {published data only}

Coen G, Gallucci MT, Bonucci E. Treatment of renal osteodystrophy (ROD) with 25‐OHD3 and 1,25 (OH)2D3: Synergic effect unrelated to 24,25 (OH)2D3 synthesis. Kidney International 1982;22(1):96.

Delmez 2000 {published data only}

Delmez JA, Kelber J, Norwood KY, Giles KS, Slatopolsky E. A controlled trial of the early treatment of secondary hyperparathyroidism with calcitriol in hemodialysis patients. Clinical Nephrology 2000;54(4):301‐8. [MEDLINE: 11076106]
Delmez JA, Kelber J, Tindira C, Norwood K, Giles K, Slatopolsky E. Long‐term effects of early use of iv calcitriol (ivc) in the prevention of secondary hyperparathyroidism (hp) in hemodialysis patients (hd) [abstract]. Journal of the American Society of Nephrology 1993;4(Program and Abstracts):695. [CENTRAL: CN‐00483717]
Delmez JA, Windus DW, Kelber J, Tindera C, Norwood K, Giles K, et al. Early administration of intravenous calcitriol(IVC) prevents secondary hyperparathyroidism(HP) in hemodialysis(HD) patients [abstract]. Journal of the American Society of Nephrology 1992;3(3):361. [CENTRAL: CN‐00460624]

Deuber 2003 {published data only}

Deuber HJ. Oral and intravenous application of alfacalcidol in the therapy of renal hyperparathyroidism [abstract]. Nephrology Dialysis Transplantation 2003;18(Suppl 4):142. [CENTRAL: CN‐00445087]

Djukanovic 1994 {published data only}

Djukanovic L, Pejanovic S, Dragojlovic Z, Stosovic M. Treatment of secondary hyperparathyroidism with intermittent oral high doses of 1‐alpha‐OHD3 plus pharmacological dose of 24,25(OH)2D3. Renal Failure 1994;16(6):715‐23. [MEDLINE: 7899583]

El‐Reshaid 1997 {published data only}

El‐Reshaid K, El‐Reshaid W, Sugathan T, Al‐Mohannadi S, Sivanandan R. Comparison of the efficacy of two injectable forms of vitamin D3 and oral One‐Alpha in treatment of secondary hyperparathyroidism in patients on maintenance hemodialysis. American Journal of Nephrology 1997;17(6):505‐10. [MEDLINE: 9426846]

Fischer 1993 {published data only}

Fischer ER, Harris DC. Comparison of intermittent oral and intravenous calcitriol in hemodialysis patients with secondary hyperparathyroidism. Clinical Nephrology 1993;40(4):216‐20. [MEDLINE: 8261678]

Fournier 1993 {published data only}

Fournier A, Moriniere P, Boudailliez B, Maurouard C, Westeel PF, Achard JM, et al. Prevention of radiologically obvious hyperparathyroidism in dialyses patients by i.v. 1alphaOH vitamin D3 (Etalpha) in association with Mg(OH)2 as sole phosphate binder. Nieren und Hochdruckkrankheiten 1993;22(1):39‐44. [EMBASE: 1993044261]
Moriniere P, Boudailliez B, Westeel PF, Achard JM, Maurouard C, Bouillon R, et al. Treatment of hyperparathyroidism in dialysis patients by intravenous 1a OH vitamin D3 in association with Mg(OH)2 as sole phosphate binder [abstract]. Nephrology Dialysis Transplantation 1991;6(10):818. [CENTRAL: CN‐00260634]
Morniere P, Maurouard C, Boudailliez B, Westeel PF, Achard JM, Boitte F, et al. Prevention of hyperparathyroidism in patients on maintenance dialysis by intravenous 1‐alpha‐hydroxyvitamin D3 in association with Mg(OH)2 as sole phosphate binder. A randomized comparative study with the association CaCO3 +/‐ Mg(OH)2. Nephron 1992;60(2):154‐63. [MEDLINE: 1552999]

Frazao 2000 {published data only}

Chesney RW, Coburn JW, 1a‐OH‐D2 Study Group. One‐alpha‐hydroxyvitamin D2 (1a‐OH‐D2): initial results from US Phase 3 trials in hemodialysis patients with secondary hyperparathyroidism [abstract]. Nephrology Dialysis Transplantation 1997;12(9):A31. [CENTRAL: CN‐00261363]
Frazao JM, Chesney RW, Coburn JW, The 1 ‐OH‐D2 Study Group. One‐alpha hydroxy‐vitamin D2 (1‐OH‐D2): an effective and safe oral agent for suppressing PTH in dialysis patients with 2o hyperparathyroidism [abstract]. Nephrology 1997;3(Suppl 1):S298. [CENTRAL: CN‐00460769]
Frazao JM, Chesney RW, Coburn JW, and the 1aD2 Study Group. Intermittent oral 1alpha‐hydroxyvitamin D2 is effective and safe for the suppression of secondary hyperparathyroidism in haemodialysis patients. Nephrology Dialysis Transplantation 1998;13(Supplement 3):68‐72. [MEDLINE: 9568825]
Frazao JM, Elangovan L, Maung HM, Chesney RW, Acchiardo SR, Bower JD, et al. Intermittent doxercalciferol (1alpha‐hydroxyvitamin D(2)) therapy for secondary hyperparathyroidism. American Journal of Kidney Diseases 2000;36(3):550‐61. [MEDLINE: 10977787]

Gadallah 2000 {published data only}

Gadallah MF, Arora N, Torres C, Ramdeen G, Schaeffer‐Pautz A, Moles K. Pulse oral versus pulse intraperitoneal calcitriol: a comparison of efficacy in the treatment of hyperparathyroidism and renal osteodystrophy in peritoneal dialysis patients. Advances in Peritoneal Dialysis 2000;16:303‐7. [MEDLINE: 11045316]

Gallieni 2000 {published data only}

Gallieni M, Brancaccio D, Antonucci F, Bellinghieri G, Carpani P, Cozzolino M, et al. Twice versus thrice weekly administration of intravenous calcitriol in dialysis patients: a randomized prospective trial. Gruppo Italiano di Studio dell'Osteodistrofia Renale. Clinical Nephrology 2000;53(3):188‐93. [MEDLINE: 10749297]
Gallieni M, Brancaccio D, Antonucci F, Bellinghieri G, Carpani P, Cozzolino M, et al. Twice versus thrice weekly administration of intraveous calcitriol in dialysis patients: a randomized prospective trial [abstract]. Journal of the American Society of Nephrology 1999;10(Program & Abstracts):618A. [CENTRAL: CN‐00550691]

Gonzalez 2003 {published data only}

Gonzalez EA, Qiu P, Silberzweig J, Hippensteel R, Fukumoto S, Williams LA, et al. Paricalcitol (Zemplar ®) capsule reduces iPTH in CKD stage 5 patients with severe (iPTH>1000) secondary hyperparathyroidism. [abstract no: F‐PO628]. Journal of the American Society of Nephrology 2003;14(Nov):199A. [CENTRAL: CN‐00583151]

Greenbaum 2005 {published data only}

Greenbaum LA, Grenda R, Qiu P, Restaino I, Wojtak A, Paredes A, et al. Intravenous calcitriol for treatment of hyperparathyroidism in children on hemodialysis. Pediatric Nephrology 2005;20(5):622‐30. [MEDLINE: 15785941]

Greenbaum 2007 {published data only}

Greenbaum LA, Benador N, Goldstein SL, Paredes A, Melnick JZ, Mattingly S, et al. Intravenous paricalcitol for treatment of secondary hyperparathyroidism in children on hemodialysis. American Journal of Kidney Diseases 2007;49(6):814‐23. [MEDLINE: 17533024]
Kommala DR, Benador N, Goldstein S, Pardes A, Mattingly S, Amdahl M, et al. Paricalcitol (Zemplar ®) injection for the treatment of secondary hyperparathyroidism in pediatric hemodialysis patients [abstract]. Journal of the American Society of Nephrology 2003;14(Nov):199A. [CENTRAL: CN‐00583154]

Haddad 2004 {published data only}

Haddad A, Abbadi R, Marji A, Akash N. Pulse intravenous vs pulse oral alfacalcidol in hemodialysis patients with secondary hyperparathyroidism. Dialysis and Transplantation 2004;33(8):492‐498,519. [EMBASE: 2004344733]

Hayashi 2004 {published data only}

Hayashi M, Tsuchiya Y, Itaya Y, Takenaka T, Kobayashi K, Yoshizawa M, et al. Comparison of the effects of calcitriol and maxacalcitol on secondary hyperparathyroidism in patients on chronic haemodialysis: a randomized prospective multicentre trial. Nephrology Dialysis Transplantation 2004;19(8):2067‐73. [MEDLINE: 15187195]
Hayashi M, Tsuchiya Y, Itaya Y, Takenaka T, Kobayashi K, Yoshizawa M, et al. Comparison of the effects of calcitriol and maxacalcitol on the secondary hyperparathyroidism in the patients on chronic hemodialysis therapy: a randomized prospective multicenter trial. [abstract]. Journal of the American Society of Nephrology 2003;14(Nov):201A. [CENTRAL: CN‐00583299]

Herrmann 1994 {published data only}

Herrmann P, Ritz E, Schmidt‐Gayk H, Schafer I, Geyer J, Nonnast‐Daniel B, et al. Comparison of intermittent and continuous oral administration of calcitriol in dialysis patients: a randomized prospective trial. Nephron 1994;67(1):48‐53. [MEDLINE: 8052367]

Indridason 2000 {published data only}

Indridason OS, Quarles LD. Comparison of calcium carbonate with oral (PO) and intravenous (IV) calcitriol in mild secondary hyperparathyroidism (HPT) [abstract]. Journal of the American Society of Nephrology 1996;7(9):1792. [CENTRAL: CN‐00445850]
Indridason OS, Quarles LD. Comparison of treatments for mild secondary hyperparathyroidism in hemodialysis patients. Kidney International 2000;57(1):282‐92. [MEDLINE: 10620210]
Indridason OS, Quarles LD. Prospective randomized trial comparing calcium carbonate (CaCO3) with oral and intravenous calcitriol in hemodialysis patients with uremic hyperparathyroidism (2ºHPT) [abstract]. Journal of the American Society of Nephrology 1997;8(Program and Abstracts):575A. [CENTRAL: CN‐00445850]

Jones 1994 {published data only}

Jones CL, Vieth R, Spino M, Ledermann S, Kooh SW, Balfe J, et al. Comparisons between oral and intraperitoneal 1,25‐dihydroxyvitamin D3 therapy in children treated with peritoneal dialysis. Clinical Nephrology 1994;42(1):44‐49. [MEDLINE: 7923966]

Khajehdehi 2003 {published data only}

Khajehdehi P, Taheri S. Effect of oral calcitriol pulse therapy on the lipid, calcium, and glucose homeostasis of hemodialysis‐patients: its safety in a combination with oral calcium carbonate. Journal of Renal Nutrition 2003;13(2):78‐83. [MEDLINE: 12671829]
Khajehdehi P, Taheri SH, Rais‐Jalali GA. Metabolic effect of oral calcitriol pulse therapy in HD patients [abstract]. Nephrology Dialysis Transplantation 2001;16(6):A85. [CENTRAL: CN‐00583859]

Kihara 2004 {published data only}

Kihara T, Ichikawa H, Morimoto H, Yano A, Akagi S, Nakao K, et al. Intravenous vitamin D therapy reduces PTH‐(1‐84)/large C fragments ratio in chronic hemodialysis patients. Nephron 2004;98(3):c93‐100. [MEDLINE: 15528944]

Klaus 1995 {published data only}

Klaus G, Hinderer J, Lingens B, Keuth B, Querfield U, Mehls O. Comparison of intermittent and continuous (daily) oral calcitriol for treatment of renal hyperparathyroidism in children on dialysis [abstract]. Pediatric Nephrology 1995;9(6):C75. [CENTRAL: CN‐00550467]

Koshikawa 2002 {published data only}

Koshikawa S, Akizawa T, Kurokawa K, Marumo F, Sakai O, Arakawa M, et al. Clinical effect of intravenous calcitriol administration on secondary hyperparathyroidism. A double‐blind study among 4 doses. Nephron 2002;90(4):413‐23. [MEDLINE: 11961400]

Lee 1994 {published data only}

Lee WT, Padayachi K, Collins JF, Cundy T. A comparison of oral and intravenous alfacalcidol in the treatment of uremic hyperparathyroidism. Journal of the American Society of Nephrology 1994;5(6):1344‐8. [MEDLINE: 7894000]

Levin 1995 {published data only}

Levin A, Carlisle E, Mendelssohn D, Jindal K, Fine A. Canadian multicenter randomized control trial (rct) comparing pulse iv and pulse oral calcitriol (c) therapy in hyperparathyroid (hpth) hemodialysis (hd) patients [abstract]. Journal of the American Society of Nephrology 1995;6(3):937. [CENTRAL: CN‐00484811]

Levine 1996 {published data only}

Levine BS, Song M. Pharmacokinetics and efficacy of pulse oral versus intravenous calcitriol in hemodialysis patients. Journal of the American Society of Nephrology 1996;7(3):488‐96. [MEDLINE: 8704116]

Liou 1994 {published data only}

Liou HH, Chiang S, Tsai S, Chang C, Wu S, Huang T, et al. Intravenous or oral calcitriol treatment in chronic hemodialysis patients with secondary hyperparathyroidism: comparative study [abstract]. Journal of the American Society of Nephrology 1993;4(Program & Abstracts):723. [CENTRAL: CN‐00484851]
Liou HH, Chiang SS, Huang TP, Shieh SD, Akmal M. Comparative effect of oral or intravenous calcitriol on secondary hyperparathyroidism in chronic hemodialysis patients. Mineral & Electrolyte Metabolism 1994;20(3):97‐102. [MEDLINE: 7816008]

Liou 1995 {published data only}

Liou H, Tsai S, Huang T. Comparative effect of subcutaneous or oral pulse calcitriol (scc, opc) treatment on secondary hyperparathyroidism in continuous ambulatory peritoneal dialysis patients (capd+shp): a prospective, crossover study [abstract]. 1995 Journal of the American Society of Nephrology;6(3):966. [CENTRAL: CN‐00484852]

Llach 1998 {published data only}

Llach F, Goldblat MV, Lindberg J, Naquin J, Delmez J, Arruda J, et al. 19‐nor‐1a, 25 ‐ dihydroxyvitamin D2 (19‐nor): an effective vitamin D analog suppresses PTH secretion in hemodialysis (HD) patients [abstract]. Nephrology 1997;3(Suppl 1):S73. [CENTRAL: CN‐00461199]
Llach F, Keshav G, Goldblat MV, Lindberg JS, Sadler R, Delmez J, et al. Suppression of parathyroid hormone secretion in hemodialysis patients by a novel vitamin D analogue: 19‐nor‐1,25‐dihydroxyvitamin D2. American Journal of Kidney Diseases 1998;32(2 (Suppl 2)):S48‐54. [MEDLINE: 9808143]

Martin 1998 {published data only}

Martin KJ, Gonzalez EA, Gellens M, Hamm LL, Abboud H, Lindberg J. 19‐Nor‐1‐alpha‐25‐dihydroxyvitamin D2 (Paricalcitol) safely and effectively reduces the levels of intact parathyroid hormone in patients on hemodialysis. Journal of the American Society of Nephrology 1998;9(8):1427‐32. [MEDLINE: 9697664]

Martin 2001 {published data only}

Martin KJ, Gonzalez E, Lindberg JS, Taccetta C, Amdahl M, Malhotra K, et al. Paricalcitol dosing according to body weight or severity of hyperparathyroidism: a double‐blind, multicenter, randomized study. American Journal of Kidney Diseases 2001;38(5 (Suppl 5)):S57‐63. [MEDLINE: 11689389]

Martinez 1996 {published data only}

Martinez J, Ballarin J, Donate T, De la Torre B, Martinez E, Molera M, et al. Once a week pulse of intravenous calcitriol in haemodialysis patients (HD) [abstract]. Nephrology Dialysis Transplantation 1996;11(6):1206. [CENTRAL: CN‐00261225]

Maxwell 1978 {published data only}

Maxwell DR, Benjamin DM, Donahay SL, Allen MK, Hamburger RJ, Luft FC. Calcitriol in dialysis patients. Clinical Pharmacology & Therapeutics 1978;23(5):515‐9. [MEDLINE: 205382]
Maxwell DR, Benjamin DM, Donahay SL, Allen MK, Hamburger RJ, Luft FC, et al. Randomized double blind study of 1, 25(OH)2D3 in dialysis patients. Proceedings of the Clinical Dialysis & Transplant Forum 1977;7:166‐9. [MEDLINE: 210446]

Memmos 1981 {published data only}

Memmos DE, Eastwood JB, Talner LB, Gower PE, Curtis JR, Phillips ME, et al. Double‐blind trial of oral 1,25‐dihydroxy vitamin D3 versus placebo in asymptomatic hyperparathyroidism in patients receiving maintenance haemodialysis. British Medical Journal Clinical Research Ed 1981;282(6280):1919‐24. [MEDLINE: 6786673]

Mitsopoulos 2006 {published data only}

Mitsopoulos E, Ginikopoulou E, Kyriklidou P, Zilidou R, Papadopoulou D, Visvardis G, et al. Initial dosing of paricalcitol based on parathormone levels in haemodialysis patients with mild and moderate secondary hyperparathyroidism: is iPTH/80 the most appropriate? [abstract]. Nephrology Dialysis Transplantation 2006;21(Suppl 4):iv135. [CENTRAL: CN‐00626107]
Mitsopoulos E, Zanos S, Ginikopoulou E, Kyriklidou P, Meimaridou D, Sakellariou G. Initial dosing of paricalcitol based on PTH levels in hemodialysis patients with secondary hyperparathyroidism. American Journal of Kidney Diseases 2006;48(1):114‐121. [MEDLINE: 16797393]

Mochizuki 2007 {published data only}

Mochizuki T, Nagamuna S, Tanaka Y, Iwamoto Y, Ishiguro C, Kawashima Y, et al. Prospective comparison of the effects of maxacalcitol and calcitriol in chronic hemodialysis patients with secondary hyperparathyroidism: a multicenter, randomized crossover study. Clinical Nephrology 2007;67(1):12‐9. [MEDLINE: 17269594]

Moe 1998 {published data only}

Moe SM, Kraus MA, Gassensmith CM, Fineberg NS, Gannon FH, Peacock M. Safety and efficacy of pulse and daily calcitriol in patients on CAPD: a randomized trial. Nephrology Dialysis Transplantation 1998;13(5):1234‐41. [MEDLINE: 9623560]

Moe 2001 {published data only}

Moe SM, Zekonis M, Harezlak J, Ambrosius WT, Gassensmith CM, Murphy CL, et al. A placebo‐controlled trial to evaluate immunomodulatory effects of paricalcitol. American Journal of Kidney Diseases 2001;38(4):792‐802. [MEDLINE: 11576883]

Moriniere 1985 {published data only}

Moriniere P, Fournier A, Leflon A, Herve M, Sebert JL, Gregoire I, et al. Comparison of 1 alpha‐OH‐vitamin D3 and high doses of calcium carbonate for the control of hyperparathyroidism and hyperaluminemia in patients on maintenance dialysis. Nephron 1985;39(4):309‐15. [MEDLINE: 3982576]

Pecovnik‐Balon 1995 {published data only}

Pecovnik‐Balon B. The effect of peroral calcitriol in small doses on mild secondary hyperparathyroidism in patients on hemodialysis. American Journal of Nephrology 1995;15(5):401‐6. [MEDLINE: 7503139]

Popovtzer 1992 {published data only}

Popovtzer MM, Levi J, Bar‐Khayim Y, Shasha SM, Boner G, Bernheim J, et al. Assessment of combined 24,25(OH)2D3 and 1 alpha (OH)D3 therapy for bone disease in dialysis patients. Bone 1992;13(5):369‐77. [MEDLINE: 1419378]
Popovzer MM, Bab I, Bar‐Haim Yl, Levi J, Boner G, Shasha S, et al. Treatment with 1 Hydroxy Vit D3 (1D) and 24‐25 dihydroxy vit D3 (24D) in haemodialysed patients [abstract]. Nephrology Dialysis Transplantation 1990;5(8):710. [CENTRAL: CN‐00260551]

Qiu 2003 {published data only}

Qiu P, Smolenski O, Fadem S, Kant KS, Borneman L, Hippensteel R, Williams LA, et al. Rapid control of secondary hyperparathyroidism with paricalcitol (Zemplar (R)) capsule in patients on peritoneal dialysis [abstract]. Journal of the American Society of Nephrology 2003;14(Nov):484A. [CENTRAL: CN‐00583207]

Quarles 1994 {published data only}

Quarles LD, Yohay DA, Carroll BA, Spritzer CE, Minda S, Lobaugh B. Prospective double‐blind placebo controlled trial of pulse oral (PO) versus intravenous (IV) calcitriol in the treatment of hyperprarthyroidism in end stage renal disease (ESRD) [abstract]. Journal of the American Society of Nephrology 1993;4(Program & Abstracts):718. [CENTRAL: CN‐00485512]
Quarles LD, Yohay DA, Carroll BA, Spritzer CE, Minda SA, Bartholomay D, et al. Prospective trial of pulse oral versus intravenous calcitriol treatment of hyperparathyroidism in ESRD. Kidney International 1994;45(6):1710‐21. [MEDLINE: 7933819]

Salusky 1998 {published data only}

Salusky IB, Goodman WG, Kuizon BD. Consequences of intermittent calcitriol therapy in pediatric patients with secondary hyperparathyroidism. Peritoneal Dialysis International 1999;19(Suppl 2):S441‐4. [MEDLINE: 10406561]
Salusky IB, Goodman WG, Kuizon BD. Implications of intermittent calcitriol therapy on growth and secondary hyperparathyroidism. Pediatric Nephrology 2000;14(7):641‐645. [MEDLINE: 10912534]
Salusky IB, Kuizon BD, Belin TR, Ramirez JA, Gales B, Segre GV, et al. Intermittent calcitriol therapy in secondary hyperparathyroidism: a comparison between oral and intraperitoneal administration. Kidney International 1998;54(3):907‐14. [MEDLINE: 9734615]

Sanchez Perales 1999 {published and unpublished data}

Sanchez Perales MC, Garcia Cortes MJ, Liebana A, Borrego FJ, Banasco P. Efficacy of a single weekly bolus of intravenous calcitriol in severe secondary hyperparathyroidism [El calcitriol intravenoso en bolo unico semanal permite mayor dosificacion y aumenta su eficacia en el hiperparatiroidismo severo en hemodialisis]. Nefrologia 1999;19(3):237‐243. [EMBASE: 1999248193]

Sprague 2003 {published data only}

Sprague SM, Lerma E, McCormmick D, Abraham M, Batlle D. Suppression of parathyroid hormone secretion in hemodialysis patients: comparison of paricalcitol with calcitriol. American Journal of Kidney Diseases 2001;38(5 Suppl 5):S51‐6. [MEDLINE: 21547704]
Sprague SM, Llach F, Amdahl M, Taccetta C, Batlle D. Paricalcitol versus calcitriol in the treatment of secondary hyperparathyroidism. Kidney International 2003;63(4):1483‐90. [MEDLINE: 12631365]

Tarrass 2006 {published data only}

Tarrass F, Yazidi A, Sif H, Zamd M, Benghanem MG, Ramdani B. A randomized trial of intermittent versus continuous oral alfacalcidol treatment of hyperparathyroidism in end‐stage renal disease. Clinical Nephrology 2006;65(6):415‐8. [MEDLINE: 16792136]

Tsuruoka 2003 {published data only}

Tsuruoka S, Yamamoto H, Saito T, Fujimara A. Chronotherapy of high‐dose vitamin D (VD) in hemodialysis patients with secondary hyperparathyroidism [abstract]. Journal of the American Society of Nephrology 2003;14(Nov):202A. [CENTRAL: CN‐00583712]

Turk 2002 {published data only}

Akbulut M, Turk S, Vatansev H, Gokbel H, Gonen S, Gurbilek M, et al. Comparison of the effects of oral and iv pulse calcitriol treatment on serum cytokine levels in hemodialysis patients [abstract]. 36th Congress. European Renal Association. European Dialysis and Transplantation Association; 1999 Sept 5‐8; Madrid (Spain). 1999:291.
Turk S, Akbuluta M, Yildiz A, Gurbilek M, Gonen S, Tombul Z, et al. Comparative effect of oral pulse and intravenous calcitriol treatment in hemodialysis patients: The effect on serum IL‐1 and IL‐6 levels and bone mineral density. Nephron 2002;90(2):188‐94. [MEDLINE: 11818704]

van der Merwe 1990 {published data only}

van der Merwe WM, Rodger RS, Grant AC, Logue FC, Cowan RA, Beastall GH, et al. Low calcium dialysate and high‐dose oral calcitriol in the treatment of secondary hyperparathyroidism in haemodialysis patients. Nephrology Dialysis Transplantation 1990;5(10):874‐7. [MEDLINE: 2128383]

Varghese 1992 {published data only}

Varghese Z, Moorhead JF, Farrington K. Effect of 24,25‐dihydroxycholecalciferol on intestinal absorption of calcium and phosphate and on parathyroid hormone secretion in chronic renal failure. Nephron 1992;60(3):286‐91. [MEDLINE: 1565181]

Watson 1989 {published data only}

Watson AR, Kooh SW, Tam C, Reilly B, Farine M, Balfe JW. The prevention of renal osteodystrophy (ROD) in children under going CAPD: a prospective randomised trial using 1 hydroxycholecalciferol [abstract]. Pediatric Nephrology 1987;1(1):C38. [CENTRAL: CN‐00448294]
Watson AR, Kooh SW, Tam CS, Reilly BJ, Balfe JW, Vieth R. Renal osteodystrophy in children on CAPD: a prospective trial of 1‐alpha‐hydroxycholecalciferol therapy. Child Nephrology and Urology 1988‐89;9(4):220‐7. [MEDLINE: 3255485]

Zisman 2005 {published data only}

Zisman AL, Ghantous W, Schinleber P, Roberts L, Sprague SM. Inhibition of parathyroid hormone: a dose equivalency study of paricalcitol and doxercalciferol. American Journal of Nephrology 2005;25(6):591‐5. [MEDLINE: 16282676]

Referencias de los estudios en curso

Ir a:

NCT00257920 {published data only}

NCT00257920. A study of Zemplar® injection and Hectorol® injection on intestinal absorption of calcium in chronic kidney disease. http://www.clinicaltrials.gov/ct2/show/NCT00257920 (accessed 3 August 2009).

NCT00397475 {published data only}

NCT00397475. Evaluation of colecalciferol substitution in dialysis patients. http://www.clinicaltrials.gov/ct2/show/NCT00397475 (accessed 3 August 2009).

Alem 2000

Alem AM, Sherrard DJ, Gillen DL, Weiss NS, Beresford SA, Heckbert SR. Increased risk of hip fracture among patients with end‐stage renal disease. Kidney International 2000;58(1):396‐9. [MEDLINE: 10886587]

Block 1998

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Referencias de otras versiones publicadas de esta revisión

Ir a:

Palmer 2006

Palmer SC, McGregor DO, Craig JC, Elder G, Strippoli GF. Vitamin D analogues for the treatment and prevention of bone disease in chronic kidney disease. Cochrane Database of Systematic Reviews 2006, Issue 1. [DOI: 10.1002/14651858.CD005633]

Palmer 2007b

Palmer SC, McGregor DO, Macaskill P, Craig JC, Elder GJ, Strippoli GF. Meta‐analysis: vitamin D compounds in chronic kidney disease. Annals of Internal Medicine 2007;147(12):840‐53. [MEDLINE: 18087055]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ir a:

Akiba 1998

Methods

  • Setting/Design: Multicentre, crossover design

  • Time frame: July 1994 to March 1996

  • Follow‐up period: 6 months

  • Loss to follow‐up: 16%

Participants

  • Country: Japan

  • Secondary hyperparathyroidism (intact PTH 200‐800 pg/mL (22‐88 pmol/L) undergoing regular HD

  • Exclusions: Serum calcium outside range 9.0‐10.5 mg/dL (2.25‐2.63 mmol/L)

Newer vitamin D group

  • Number: 13

  • Age: 53.8 (2.7 SD) years

  • Sex (M/F): 6/7

Established vitamin D group

  • Number: 12

  • Age: 51.2 (1.9 SD) years

  • Sex (M/F): 4/8

Interventions

Newer vitamin D group

  • Falecalcitriol: 0.15‐3 µg/d orally for 24 weeks

Established vitamin D group

  • Alfacalcidol: 0.25‐0.5 µg/d orally for 24 weeks

Cointerventions: NS

Outcomes

Extractable and relevant to this review

  • All‐cause mortality

  • Hypercalcaemia (serum calcium > 10.5 mg/dL (2.63 mmol/L))

  • Withdrawal from treatment due to hypercalcaemia (serum calcium > 10.5 mg/dL (2.63 mmol/L))

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • 2 (treatment assignment NS)

  • Stop or endpoint/s

    • Post hoc: cerebral infarction (alfacalcidol, treatment period 1), arthralgia and uncontrolled serum phosphorus levels (falecalcitriol, treatment period 1), uncontrolled serum calcium levels and need for parathyroidectomy (alfacalcidol, treatment period 2)

  • Additional data requested and/or received from authors

    • Allocation concealment, number of fractures in each group, mean end of treatment PTH, calcium, phosphorus, and calcium x phosphorus concentrations

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 25

    • Analysed: 21

    • Per cent follow‐up: 84

The study used a crossover design, with both interventions prescribed to each group randomly in reverse order, without washout period.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Central dynamic allocation method using serum calcium and iPTH concentrations during 8‐week observation period and institution as stratification variables

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

High risk

No blinding of participants or investigators. Blinding of outcome assessors or data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

High risk

ITT not performed

Was the study free of potential bias from the funding source?

High risk

Funded by a pharmaceutical company
Akizawa 2004

Methods

  • Setting/Design: Multicentre

  • Time frame: NS

  • Follow‐up period: 3 months

  • Loss to follow‐up: 16%

Participants

  • Country: Japan

  • Age 20‐75 years, stable on HD with secondary hyperparathyroidism (iPTH > 200 pg/mL (22pmol/L)); serum calcium 9.0‐10.5 mg/dL (2.25‐2.63 mmol/L), serum phosphorus > 7.0 mg/dL (2.3mmol/L)

  • Exclusions: Primary hyperparathyroidism; serious cardiac or hepatic disorders; malignant neoplasms; serious infectious diseases; specific conditions such as drug allergies or marked aluminium accumulation; pregnant or lactating women

Newer vitamin D group 1

  • Number: 56

  • Age: 49.4 (10.6 SD) years

  • Sex (M/F): 32/24

Newer vitamin D group 2

  • Number: 47

  • Age: 50.0 (9.9 SD) years

  • Sex (M/F): 31/16

Newer vitamin D group 3

  • Number :47

  • Age: 50.1 (10.6 SD) years

  • Sex (M/F): 28/19

Placebo group

  • Number: 26

  • Age: 53.4 (10.7 SD) years

  • Sex (M/F): 14/12

Interventions

Newer vitamin D group 1

  • 22‐oxacalcitriol: 5 µg IV thrice weekly

Newer vitamin D group 2

  • 22‐oxacalcitriol: 10 µg IV thrice weekly

Newer vitamin D group 3

  • 22‐oxacalcitriol: 15 µg IV thrice weekly

Placebo group

  • Placebo IV thrice weekly (in identical vials)

Cointerventions: Calcium carbonate or aluminium containing phosphate binders

Outcomes

Extractable and relevant to this review

  • Hypercalcaemia (> 11.5 mg/dL (2.88 mmol/L))

  • Suppression of iPTH > 30% from baseline value

Notes

  • Exclusions post‐randomisation but pre‐intervention: NS

  • Stop or endpoint/s

    • Discontinuation if corrected serum calcium concentration > 11.5 mg/dL (2.88 mmol/L)

  • Additional data requested and/or received from authors

    • Allocation concealment, blinding, compliance, fracture events during follow‐up, per cent reduction iPTH > 30%, end of treatment iPTH, serum calcium, and serum phosphorus concentrations

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised:203

    • Analysed: 176

    • Per cent follow‐up: 84%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Central dynamic allocation, stratified by iPTH concentration, corrected serum calcium level, age, and centre.

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Blinding of participants or investigators. Blinding of outcome assessors or data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

Low risk

ITT performed

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Bacchini 1997

Methods

  • Setting/Design: Single centre

  • Time frame: NS

  • Follow‐up period: 4 months

  • Loss to follow‐up: 0%

Participants

  • Country: Italy

  • HD, 18‐66 years, iPTH 200‐2 500 ng/mL (22‐285 pmol/L)

  • Exclusions: Type 1 diabetes; prior parathyroidectomy; phenobarbital; phenytoin; glucocorticoids; inadequate dialysis; serum Al > 100 µg/L; serum ionised calcium > 5.52 mg/dL (1.38 mmol/L)

IV group

  • Number: 10

  • Age: 52.7 (19 SD) years

  • Sex (M/F): 5/5

Oral group

  • Number: 10

  • Age: 50.6 (12 SD) years

  • Sex (M/F): 7/3

Interventions

IV group

  • Four‐month washout without calcitriol.

  • IV calcitriol: 0.5 µg thrice weekly increased according to ionised calcium fortnightly for 16 weeks

Oral group

  • Oral calcitriol: 0.5 µg thrice weekly increased according to ionised serum calcium fortnightly for 16 weeks

Cointerventions: Alteration of dialysate calcium concentration and oral calcium carbonate

Outcomes

Extractable and relevant to this review

  • Hypercalcaemia (ionised calcium > 5.52 mg/dL (1.38 mmol/L))

  • Hyperphosphataemia (> 5.26 mg/dL (> 1.70 mmol/L))

  • End of treatment plasma PTH concentration

  • End of treatment serum calcium concentration

  • End of treatment phosphorus concentration

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • Nil

  • Stop or endpoint/s

    • Nil

  • Additional data requested and/or received from authors

    • Allocation concealment, blinding methods, all‐cause mortality and fracture events, mean end of treatment PTH concentration.

  • Completeness of follow‐up

    • Eligible/considered for inclusion: 204

    • Enrolled/randomised: 20

    • Analysed: 20

    • Per cent follow‐up:100%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Not stated

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Baker 1986

Methods

  • Setting/Design: Two centre study

  • Time frame: March 1977 to January 1982

  • Follow‐up period: 5 years

  • Loss to follow‐up: 46%

Participants

  • Country: UK

  • Adults requiring HD without radiological or biochemical evidence of bone disease

  • Exclusions: Treatment with vitamin D derivative in previous 3 months; anticonvulsant or steroid therapy; previous parathyroidectomy

Established vitamin D group

  • Number: 38

  • Age: NS

  • Sex (M/F): NS

Placebo group

  • Number: 38

  • Age: NS

  • Sex (M/F): NS

Interventions

Established vitamin D group

  • Oral calcitriol: 0.25‐1 µg/d

Placebo group

  • Placebo

Cointerventions: Aluminium containing phosphate binders, dialysis 15‐24 hours/week, dialysate calcium concentration 6.6 mg/dL (1.65 mmol/L), daily dietary calcium intake 48‐76 mg (12‐19 mmol)

Outcomes

Extractable and relevant to this review

  • Fracture

  • Parathyroidectomy

  • Development of subperiosteal erosions

  • Development of vascular calcification

  • Progression of vascular calcification

  • Treatment‐related toxicity

  • Withdrawal of treatment due to hypercalcaemia (11 mg/dL (2.75 mmol/L))

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • Immobilization, major surgery including transplantation (20), persistent hypercalcaemia (8), unacceptable side‐effects

  • Additional data requested and/or received from authors

    • Method of randomisation and allocation concealment, all‐cause mortality events, end of treatment PTH concentration

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 76

    • Analysed (bone biopsy): 20

    • Per cent follow‐up: 9% remaining in study at 60 months

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated, stratified by time on dialysis, age, plasma alkaline phosphatase, the presence or absence of kidneys, and centre of care.

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Blinding of participants or investigators. Blinding of outcome assessors or data assessors not stated

Intention‐to‐treat analysis ‐ was it performed?

High risk

Not performed

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated.
Berl 1980

Methods

  • Setting/Design: Three dialysis centres

  • Time frame: NS

  • Follow‐up period: 3 months

  • Loss to follow‐up: NS

Participants

  • Country: USA

  • Regular HD, without regard for clinical or biochemical evidence for bone disease

  • Exclusions: Serum calcium > 10 mg/dL (2.5 mmol/L) or non compliance

Established vitamin D group 1

  • Number: 16

  • Age: 48 (3.4 SD) years

  • Sex (M/F): 8/8

Established vitamin D group 2

  • Number: 15

  • Age: 45 (2.5 SD) years

  • Sex (M/F): 7/8

Interventions

Established vitamin D group 1

  • Oral calcitriol: 0.5‐1.5 µg/d

Established vitamin D group 2

  • Oral vitamin D: 400 IU/d

Cointerventions: Stable dialysate calcium (6 mg/dL (1.5 mmol/L)), aluminium containing antacids to maintain serum phosphorus between 4.0‐7.0 mg/dL (1.3‐2.3 mmol/L)

Outcomes

Extractable and relevant to this review

  • Bone pain

  • Bone histomorphometry parameters

  • End of treatment serum calcium, phosphorus and alkaline phosphatase concentrations

  • Hypercalcaemia, (serum calcium > 11.5 mg/dL (2.88 mmol/L))

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • NS

  • Additional data requested and/or received from authors

  • ITT analyses, all‐cause mortality events, fracture events, end of treatment serum phosphorus concentrations

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 31

    • Analysed: 28

    • Per cent follow‐up: 90%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Computed‐generated random sequence

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Low risk

Blinding of participants, investigators and outcomes assessors. Blinding of data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

High risk

Funded by pharmaceutical company
Borazan 2003

Methods

  • Setting/Design: Two university centres

  • Time frame: NS

  • Follow‐up period: 6 months

  • Loss to follow‐up: 0%

Participants

  • Country: Turkey

  • HD patients with secondary hyperparathyroidism

  • Exclusions: NS

Oral group

  • Number: 18

  • Age: 39.8 (13.4 SD) years

  • Sex (M/F): 9/9

IV group

  • Number: 16

  • Age: 38.7 (14.3 SD) years

  • Sex (M/F): 7/9

Interventions

Oral group

  • Oral calcitriol: 0.5 µg/d

IV group

  • IV calcitriol: 1 µg/thrice weekly

Cointerventions: Dialysate calcium 6.8 mg/dL (1.7 mmol/L)

Outcomes

Extractable and relevant to this review

  • Episodes of hypercalcaemia (serum calcium > 11.5 mg/dL (2.88 mmol/L))

  • End of treatment PTH concentration

  • End of treatment serum calcium, alkaline phosphatase concentration

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • Nil

  • Additional data requested and/or received from authors

    • Method for randomisation, allocation concealment, blinding, or compliance assessment, all‐cause mortality and fracture events, end of serum phosphorus concentration.

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 34

    • Analysed: 34

    • Per cent follow‐up 100%

Ethics approval was not sought for study.

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Blinding of participants, investigators, outcome assessors or data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

Low risk

ITT performed

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Buccianti 1981

Methods

  • Setting/Design: University centre

  • Time frame: NS

  • Follow‐up period: 6 months

  • Loss to follow‐up: 29/48 lost to bone biopsy follow‐up

Participants

  • Country: Italy

  • Maintenance HD

  • Exclusions: NS

Established vitamin D group 1

  • Number: 24

  • Age: 48 years

  • Sex (M/F): 14/10

Established vitamin D group 2

  • Number: 24

  • Age: 47 years

  • Sex (M/F): 17/7

Interventions

Established vitamin D group 1

  • Oral 25(OH)D3: 50 µg/d

Established vitamin D group 2

  • Oral calcitriol: 0.5 µg/d

Cointerventions: NS

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • Nil

  • Stop or endpoint/s

    • NS

  • Additional data requested and/or received from authors

    • Methods for randomisation, allocation concealment, ITT analysis, and blinding, and number followed up.

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 65

    • Analysed: 29/65 bone biopsy

    • Per cent follow‐up: 100% (authors state patients who required dose adjustment were excluded; unclear whether excluded pre or post randomisation)

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Blinding of participants, investigators, outcome assessors or data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Caravaca 1995

Methods

  • Setting/Design: Single regional university centre

  • Time frame: NS

  • Follow‐up period: 2.5 months

  • Loss to follow‐up: 24%

Participants

  • Country: Spain

  • HD requiring, basal iPTH > 4 times normal range

  • Exclusions: NS

Intermittent group 1

  • Number: 11

  • Age: NS

  • Sex (M/F): NS

Intermittent group 2

  • Number: 8

  • Age: NS

  • Sex (M/F): NS

Daily group

  • Number: 7

  • Age: NS

  • Sex (M/F): NS

Interventions

Intermittent group 1

  • IV calcitriol: 0.045 µg/wk

Intermittent group 2

  • Oral calcitriol: 0.045 µg/wk

Daily group

  • Oral calcitriol: 0.045 µg/wk

Cointerventions: Calcium carbonate, calcium acetate, aluminium hydroxide

Outcomes

Extractable and relevant to this review

  • Hyperphosphataemia (serum phosphorus > 7 mg/dL (2.25 mmol/L))

  • End of treatment serum calcium, phosphorus, PTH, alkaline phosphatase

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • Post hoc: kidney transplantation (4), death (1), intensification of pruritus (1), clinical instability (1)

  • Additional data requested and/or received from authors

    • Methods (allocation concealment, randomisation, blinding, compliance assessment, ITT analysis), death and fracture events.

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 31

    • Analysed: 26

    • Per cent follow‐up: 84%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated, stratified according to PTH

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Blinding of participants, investigators, outcome assessors or data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

High risk

Not performed

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Coen 1982

Methods

  • Setting/Design: NS

  • Time frame: NS

  • Follow‐up period: 6‐12 months

  • Loss to follow‐up: 0%

Participants

  • Country: Italy

  • Regular HD

  • Exclusions: Serum calcium > 10 mg/dL (> 2.5 mmol/L)

Intermittent group

  • Number: 16

  • Age: 48 (3.4 SD) years

  • Sex (M/F): 8/8

Daily group

  • Number: 15

  • Age: 45 (2.5 SD) years

  • Sex (M/F): 7/8

Interventions

Intermittent group

  • Oral calcitriol: 2.75 µg once weekly and 2.5 µg once weekly

Daily group

  • Oral calcitriol: 0.75 µg daily

Cointerventions: Calcium carbonate, calcium acetate, aluminium hydroxide

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • NS

  • Additional data requested and/or received from authors

    • Methods (allocation concealment, blinding, compliance), mortality and fracture events, and end of treatment serum PTH, calcium, and phosphorus concentrations.

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 15

    • Analysed: NS

    • Per cent follow‐up: NS

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Blinding of participants, investigators, outcome assessors or data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Delmez 2000

Methods

  • Setting/Design: Single university centre

  • Time frame: NS

  • Follow‐up period: 12months

  • Loss to follow‐up: 0%

Participants

  • Country: USA

  • HD therapy < one year and lack of severe hyperparathyroidism, N‐PTH level < 600 pg/mL (68 pmol/L)

  • Exclusions: Hypercalcaemia > 11 mg/dL (2.75 mmol/L) and hyperphosphataemia > 6.5 mg/dL (2 mmol/L), uncontrolled hypertension (blood pressure > 180/100), treatment with digoxin or prior parathyroidectomy

Established vitamin D group

  • Number: 7

  • Age: 57 (13 SD) years

  • Sex (M/F): 2/5

No treatment group

  • Number: 8

  • Age: 53 ( 16 SD) years

  • Sex (M/F): 4/4

Interventions

Established vitamin D group

  • IV calcitriol: 2 µg after each dialysis. If hypercalcaemia occurred (calcium > 11mg/dL) the calcitriol dose was decreased to 1 µg/treatment, if hypercalcaemia reoccurred then the dose was reduced to 0.5 µg/treatment.

No treatment group

  • No treatment

Cointerventions: Calcium carbonate and aluminium hydroxide

Outcomes

Extractable and relevant to this review

  • Fracture at any site

  • Development of bone pain

  • Episodes of hypercalcaemia (calcium > 11mg/dL (2.75 mmol/L))

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • 5 participants

  • Stop or endpoint/s

    • NS

  • Additional data requested and/or received from authors

    • Methods (allocation concealment, blinding, compliance), death events, end of treatment serum PTH, calcium, and phosphorus concentrations.

  • Completeness of follow‐up

    • Eligible/considered for inclusion: 20

    • Enrolled/randomised: 15

    • Analysed: 15

    • Per cent followed: 100%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

High risk

According to whether their patient number was even or odd.

Allocation concealment?

High risk

Inadequate

Blinding?
All outcomes

Unclear risk

Blinding of participants, investigators, outcome assessors or data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

High risk

Not performed

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Deuber 2003

Methods

  • Setting/Design: NS

  • Time frame: NS

  • Follow‐up period: 36 months

  • Loss to follow‐up: NS

Participants

  • Country: Germany

  • HD therapy

  • Exclusions: NS

Established vitamin D group 1

  • Number: 25

  • Age: NS

  • Sex (M/F): NS

Established vitamin D group 2

  • Number: 25

  • Age: NS

  • Sex (M/F): NS

Interventions

Established vitamin D group 1

  • Alfacalcidol: 3.8 ± 0.4 µg/wk

Established vitamin D group 2

  • Calcitriol: 2.7 ± 0.5 µg/wk

Cointerventions: NS

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • During 36 months of therapy 10 patients in alfacalcidol group and 16 in calcitriol group were switched to IV alfacalcidol (due to increased PTH concentrations)

  • Additional data requested and/or received from authors

    • None

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 50

    • Analysed: NS

    • Percent followed: NS

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Blinding of participants, investigators, outcome assessors or data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Djukanovic 1994

Methods

  • Setting/Design: Single centre

  • Time frame: NS

  • Follow‐up period: 24 weeks

  • Loss to follow‐up: 0%

Participants

  • Country: Yugoslavia

  • HD patients with PTH concentration > 3 times upper limit of normal

  • Exclusions: NS

Established vitamin D group 1

  • Number: 10

  • Age: 53 (9.6 SD) years

  • Sex (M/F): 4/6

Established vitamin D group 2

  • Number: 10

  • Age: 54 (12.8 SD) years

  • Sex (M/F): 6/4

Interventions

Established vitamin D group 1

  • 1a‐hydroxyvitamin D3: Commencing with 1 µg orally 3 times weekly in combination with 1,25 (OH)2D3 10 µg/d.

Established vitamin D group 2

  • 1‐a‐hydroxyvitamin D3: Commencing with 1 µg orally 3 times weekly

Cointerventions: Calcium carbonate, aluminium hydroxide

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • Methods (randomisation, allocation concealment, blinding, compliance assessment, ITT analyses), death and fracture events, hypercalcaemia events, end of treatment serum phosphorus and calcium concentrations

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 20

    • Analysed: 20

    • Per cent follow‐up: 100%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Blinding of participants, investigators, outcome assessors or data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
El‐Reshaid 1997

Methods

  • Setting/Design: Single university dialysis centre, crossover study design

  • Time frame: NS

  • Follow‐up period: 3 months

  • Loss to follow‐up: 0%

Participants

  • Country: Kuwait

  • Maintenance HD for a minimum of one year

  • Exclusions: Diabetes mellitus; chronic infection; liver disease; malabsorption syndrome; autoimmune disease; immunosuppressive therapy; previous kidney transplantation or parathyroidectomy; patients receiving antiepileptic drugs or drugs known to interfere with hepatic enzymes.

Established vitamin D group 1

  • Number: 10

  • Age: 39 (12 SD) years

  • Sex (M/F): 8/2

Established vitamin D group 2

  • Number: 10

  • Age: 40 (10 SD) years

  • Sex (M/F): 8/2

Interventions

Established vitamin D group 1

  • IV calcitriol: 1 µg dialysis treatment

Established vitamin D group 2

  • IV 1‐alpha OH vitamin D3: 1 µg/dialysis treatment

Cointerventions: Calcium gluconate PO and other unspecified phosphate binders

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • Methods (randomisation, allocation concealment, blinding, assessment of compliance, ITT analyses), death and fracture events, end of treatment serum phosphorus, calcium and PTH concentrations (for first period of study).

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 20

    • Analysed: 20

    • Per cent followed: 100%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated, matched for age, gender, and dialysis vintage

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Blinding of participants, investigators, outcome assessors or data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Fischer 1993

Methods

  • Setting/Design: Single hospital centre, crossover study design

  • Time frame: NS

  • Follow‐up period: 4 months

  • Loss to follow‐up: 9%

Participants

  • Country: Australia

  • Maintenance HD

  • Exclusions: NS

IV group

  • Number: 6

  • Age: NS

  • Sex (M/F): NS

Oral group

  • Number: 5

  • Age: NS

  • Sex (M/F): NS

Interventions

IV group

  • IV calcitriol: 2 µg thrice weekly

Oral group

  • Oral calcitriol: 2 µg thrice weekly

Cointerventions: Dialysate calcium reduction when hypercalcaemia occurred. No calcium containing phosphate binders were used.

Outcomes

Extractable and relevant to this review

  • Fracture

  • Hypercalcaemia (serum calcium > 10.8 mg/dL (2.7 mmol/L))

  • End of treatment serum calcium, phosphorus, PTH concentration

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • Nil

  • Stop or endpoint/s

    • NS

  • Additional data requested and/or received from authors

    • Methods (allocation concealment, randomisation, blinding, ITT), fracture events, hypercalcaemia events, serum PTH, calcium, phosphorus concentrations (for end of first period of treatment)

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised:11

    • Analysed:10

    • Per cent followed: 91%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Coin toss by nursing staff

Allocation concealment?

High risk

Inadequate

Blinding?
All outcomes

Unclear risk

No blinding of participants, investigators, outcome assessors or data assessors

Intention‐to‐treat analysis ‐ was it performed?

Low risk

ITT performed

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Fournier 1993

Methods

  • Setting/Design: Single dialysis unit

  • Time frame: NS

  • Follow‐up period: 6 months

  • Loss to follow‐up: 13%

Participants

  • Country: France

  • Requiring HD

  • Exclusions: NS

Established vitamin D group

  • Number: 23

  • Age: 63 (11 SD) years

  • Sex (M/F): 11/12

Calcium group

  • Number: 24

  • Age: 61.4 (12 SD) years

  • Sex (M/F): 13/11

Interventions

Established vitamin D group

  • IV 1‐alpha‐hydroxyvitamin D3: 1‐4 µg thrice weekly

Calcium group

  • Oral calcium carbonate: Titrated to plasma calcium and phosphorus, 25‐hydroxyvitamin D3

Cointerventions: Magnesium hydroxide

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Exclusions after randomisation but before analyses

    • Calcium group (1 patient, kidney transplant); 1‐alpha‐hydroxyvitamin D3 group (5 patients, 2 uncontrollable hyperphosphataemia, 1 cerebrovascular event, 2 deaths)

  • Stop or endpoint/s

    • NS

  • Additional data requested and/or received from authors:

    • Methods (allocation concealment, randomisation, blinding), fracture events, end of treatment PTH concentration

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 47

    • Analysed: 41

    • Per cent followed: 87%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Blinding of participants, investigators, outcome assessors or data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Frazao 2000

Methods

  • Setting/Design: 18 HD units

  • Time frame: NS

  • Follow‐up period: 2 months

  • Loss to follow‐up: 0%

Participants

  • Country: USA

  • 18‐65 years; thrice weekly HD; HD > 6months; serum PTH > 250‐500 pg/mL (28.5‐55 pmol/L) and > 500 pg/mL (> 55 pmol/L)

  • Exclusions: Prior therapy with vitamin D analogues in doses exceeding 0.5 µg/d; prior parathyroidectomy; treatment in prior 6 months with medications that may interfere with vitamin D or bone homeostasis; serum calcium > 10.5 mg/dL (2.63 mmol/L); serum phosphorus > 7 mg/dL (2.26 mmol/L)

Newer vitamin D group

  • Number: 71

  • Age: 55 (12.4 SD) years

  • Sex (M/F): 35/36

Placebo group

  • Number: 67

  • Age: 49 (14.9 SD) years

  • Sex (M/F): 33/34

Interventions

Newer vitamin D group

  • Oral doxercalciferol: 10 µg with each HD session 8 weeks, dose titrated to plasma iPTH 150‐300 pg/mL (16.5‐33 pmol/L)

Placebo group

  • Placebo

Cointerventions: Calcium carbonate, calcium acetate

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Exclusions post‐randomisation, during treatment

    • Doxercalciferol: 13 patients (3 protocol violations, 8 hyperphosphataemia (mean serum phosphorus > 6.9 mg/dL (2.23 mmol/L)), 1 cardiac death, 1 change in dialysis modality)

    • Placebo: 7 patients (3 protocol violations, 1 mean serum phosphorus > 6.9 mg/dL (2.23 mmol/L), 2 cardiac deaths, 1 parathyroidectomy)

  • Stop or endpoint/s

    • Treatment suspended temporarily if iPTH level fell below "target range (150‐300 pg/mL (16.5‐33 pmol/L)), serum calcium > 11.2 mg/dL (2.8 mmol/L), serum phosphorus > 8.0 mg/dL (2.58 mmol/L) or calcium x phosphorus product > 75.0.

  • Additional data requested and/or received from authors

    • Allocation concealment, fracture events, end of treatment serum calcium and phosphorus concentrations, hypercalcaemia events during treatment.

  • Completeness of follow‐up

    • Eligible/considered for inclusion: 211

    • Enrolled/randomised:138

    • Analysed: 99

    • Per cent followed: 72%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Remote randomisation (centrally located, unaffiliated statistician, who used a randomisation code).

Allocation concealment?

Low risk

Adequate

Blinding?
All outcomes

Unclear risk

Blinding of participants and investigators. Blinding of outcome assessors or data assessors not stated

Intention‐to‐treat analysis ‐ was it performed?

High risk

Not performed

Was the study free of potential bias from the funding source?

High risk

Funded by pharmaceutical company
Gadallah 2000

Methods

  • Setting/Design: NS

  • Time frame: NS

  • Follow‐up period: 48 months

  • Loss to follow‐up: 55%

Participants

  • Country: USA

  • Prevalent adults requiring CCPD

  • Exclusions: NS

IP group

  • Number: 18

  • Age: NS

  • Sex (M/F): NS

Oral group

  • Number: 16

  • Age: NS

  • Sex (M/F): NS

Interventions

IP group

  • IP calcitriol: 3‐6 mg/wk in divided doses with 6 hour dwell time

Oral group

  • Oral calcitriol: 3‐6 mg/wk in divided doses

Cointerventions: Adjustment of dialysate calcium

Outcomes

Extractable and relevant to this review

  • Improvement in bone histomorphometry

  • End of treatment PTH concentration

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • NS

  • Additional data requested and/or received from authors

    • None

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised:76

    • Analysed: 34

    • Per cent followed: 45%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

High risk

According to date of entry into dialysis program

Allocation concealment?

High risk

Inadequate

Blinding?
All outcomes

High risk

No blinding of participants, investigators, outcome assessors or data assessors.

Intention‐to‐treat analysis ‐ was it performed?

High risk

Not performed

Was the study free of potential bias from the funding source?

Unclear risk

Not stated
Gallieni 2000

Methods

  • Setting/Design: 5 HD centres

  • Time frame: NS

  • Follow‐up period: 3 months

  • Loss to follow‐up: 4/22 (18%)

Participants

  • Country: Italy

  • Dialysis treatment for at least 3 months; 3 times weekly; age >15 years; good compliance; phosphate binders = calcium carbonate or acetate; aluminium hydroxide <2 g/d; laboratory criteria including PTH level 400‐900 pg/mL (44‐100 pmol/L); calcium level 8.5‐10.5 mg/dL (2.1‐2.6 mmol/L)

  • Exclusions: Treatment with active vitamin D metabolites in the 4 weeks prior to the study; recent bone fracture; pregnancy; cancer; sarcoidosis; Paget's disease; parathyroidectomy; anticonvulsants or corticosteroids; severe hypertension (diastolic blood pressure > 110 mm Hg)

Thrice weekly group

  • Number: 10

  • Age: mean age NS

  • Sex (M/F): 4/6

Twice weekly group

  • Number: 12

  • Age: mean age NS

  • Sex (M/F): 5/7

Interventions

Thrice weekly group

  • IV calcitriol: 3‐6 µg/wk in three divided doses

Twice weekly group

  • IV calcitriol IV 3‐6 µg/wk in two divided doses

Cointerventions: Aluminium‐containing phosphate binders

Outcomes

Extractable and relevant to this review

  • Fracture

  • Hypercalcaemia (serum calcium > 10.8 mg/dL (2.7 mmol/L))

  • End of treatment serum calcium, phosphorus, PTH concentrations

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • Calcium x phosphorus product > 70 mg²/dL² or calcium > 11.0 mg/dL (2.75 mmol/L)

  • Additional data requested and/or received from authors

    • None

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 22

    • Analysed: 18

    • Per cent follow‐up: 82%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

High risk

No blinding of participants, investigators, outcome assessors or data assessors

Intention‐to‐treat analysis ‐ was it performed?

Low risk

ITT performed

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Gonzalez 2003

Methods

  • Setting/Design: Multicentre studies (combined data from 3 pooled RCTs)

  • Time frame: NS

  • Follow‐up period: 12 weeks

  • Loss to follow‐up: NS

Participants

  • Country: USA

  • CKD stage 5 with severe secondary hyperparathyroidism on dialysis

  • Exclusions: NS

Newer vitamin D group

  • Number: 15

  • Age: NS

  • Sex (M/F): NS

Placebo group

  • Number: 11

  • Age: NS

  • Sex (M/F): NS

Interventions

Newer vitamin D group

  • Paricalcitol (initial dose = iPTH/60) with maximum initial dose of 32 µg, titrated in 2 µg increments based on baseline calcium, calcium x phosphorus product, and iPTH

Placebo group

  • Placebo

Cointerventions: NS

Outcomes

Extractable and relevant to this review

  • Suppression of iPTH > 30% below baseline value

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • Efficacy end point: At least 2 consecutive ≥ 30% decrease in PTH from baseline

  • Additional data requested and/or received from authors

    • None

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 26

    • Analysed: 26

    • Per cent followed: 100%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Blinding of participants and investigators. Blinding of outcome assessors or data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

High risk

Funded by Abbott Laboratories
Greenbaum 2005

Methods

  • Setting/Design: Multicentre study

  • Time frame: During 1999

  • Follow‐up period: up to 12 weeks

  • Lost to follow‐up: 19 (40%)

Participants

  • Country: USA

  • Paediatric patients (2‐18 years); on maintenance HD; serum calcium < 10.5 mg/dL (< 2.63 mmol/L); Ca X P< 70 mg²2/dL², two consecutive iPTH < 400 pg/mL (44 pmol/L)

  • Exclusions: Post pubescent; pregnant or nursing; allergy to calcitriol; concurrent growth hormone therapy; partial parathyroidectomy within previous year; AKI within 3 months; at risk of aluminium‐related bone disease or required aluminium containing phosphate binder or sevelamer for > 3 weeks of the study

Established vitamin D group

  • Number: 21

  • Age: 15.3 (2.8 SD) years

  • Sex (M/F): 14/7

Placebo group

  • Number: 26

  • Age: 14.0 (3.8 SD) years

  • Sex (M/F): 17/9

Interventions

Established vitamin D group

  • Calcitriol: Initial dose based on plasma iPTH (iPTH < 500 pg/mL (55 pmol/L) initial dose 0.5 µg/d; iPTH 500‐1000 pg/mL (55‐110 pmol/L) initial dose 1 µg/d), iPTH > 1000 pg/mL (> 110 pmol/L) 1.5 µg/d

Placebo group

  • Placebo

Cointerventions: Calcium‐containing phosphate binders

Outcomes

Extractable and relevant to this review

  • Hypercalcaemia (serum calcium > 10.5 mg/dL (2.63 mmol/L))

  • Hyperphosphataemia (serum phosphorus > 6.5 mg/dL (2.1 mmol/L))

  • Raised calcium x phosphorus product (> 75 mg²/dL²)

  • Suppression of iPTH > 30% below baseline value

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • Nil

  • Stop or endpoint/s

    • Two consecutive PTH concentrations > 800 pg/mL (88 pmol/L) if this concentration represented an increase from baseline.

  • Additional data requested and/or received from authors

    • None

  • Completeness of follow‐up

    • Eligible/considered for inclusion:72

    • Enrolled/randomised: 47

    • Analysed: 28

    • Per cent followed: 59.6%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Blinding of participants and investigators. Blinding of outcome assessors or data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

High risk

Funded by Abbott Laboratories
Greenbaum 2007

Methods

  • Setting/Design: 11 sites

  • Time frame: 2002‐2003

  • Follow‐up period: 12 weeks

  • Lost to follow‐up: 0%

Participants

  • Country: USA

  • Paediatric patients (2 to 20 years) undergoing maintenance HD therapy 3 times/wk for more than 1 month.

  • Exclusions: Pregnant or nursing; history of allergy to paricalcitol; underwent partial parathyroidectomy within 1 year or AKI within 3 months; at risk of aluminium‐related bone disease; aluminium containing for longer than 3 weeks during 3 months before the study; active malignancy; HIV infection; clinically significant liver disease; recent history of drug or alcohol abuse; scheduled for kidney transplant within 16 weeks study initiation; investigational drug within 30 days; concurrent disease or condition that would prohibit completion of study; history poor compliance with diet, medication or HD; on maintenance calcitonin, glucocorticoid; other drug therapy that might affect indices of bone and mineral metabolism.

Newer vitamin D group

  • Number: 15

  • Age: 13.6 (4.8 SD) years

  • Sex (M/F): 13/2

Placebo group

  • Number: 14

  • Age: 14.3 (4.1 SD) years

  • Sex (M/F): 9/5

Interventions

Newer vitamin D group

  • IV paricalcitol: 3 times/wk initial dose based on initial iPTH levels

Placebo group

  • Placebo

Cointerventions: Calcium carbonate, calcium acetate, sevelamer hydrochloride, and maintain dialysate calcium levels at 2.5 mEg/L (1.25 mmol/L)

Outcomes

Extractable and relevant to this review

  • Hypercalcaemia (one or more serum calcium level > 11.2 mg/dL (> 2.79 mmol/L))

  • Reduction in PTH (two consecutive 30% decreases from baseline iPTH levels)

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • Nil

  • Stop or endpoint/s

    • Discontinuation after 4 weeks treatment if they have 2 consecutive iPTH levels > 700 pg/mL (77 pmol/L) and if these levels represented an increase from baseline.

  • Additional data requested and/or received from authors

    • None

  • Completeness of follow‐up

    • Eligible/considered for inclusion: 46

    • Enrolled/randomised: 29

    • Analysed: 29

    • Completed treatment: 12 (41%)

    • Per cent follow‐up: 100%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Blinding of participants and investigators. Blinding of outcome assessors or data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

Low risk

ITT performed

Was the study free of potential bias from the funding source?

High risk

Funded by Abbott Laboratories
Haddad 2004

Methods

  • Setting/Design: Single dialysis centre

  • Time frame: NS

  • Follow‐up period: 3 months

  • Loss to follow‐up: 4/26 (15%)

Participants

  • Country: Jordan

  • 18‐65 years; thrice weekly HD; HD > 6months

  • Exclusions: Prior therapy with vitamin D analogues in doses exceeding 0.5 µg/d; prior parathyroidectomy; treatment in prior 6 months with medications that may interfere with vitamin D or bone homeostasis; serum calcium > 10.5 mg/dL (2.63 mmol/L); serum phosphorus > 7 mg/dL (2.26 mmol/L)

IV group

  • Number: 12

  • Age: NS

  • Sex (M/F): 5/7

Oral group

  • Number: 13

  • Age: NS

  • Sex (M/F): 7/5

Interventions

IV group

  • IV alphacalcidol: 1‐4µg thrice weekly titrated to serum calcium and phosphorus

Oral group

  • Oral alphacalcidol: 1‐4 µg thrice weekly titrated to serum calcium and phosphorus

Cointerventions: NS

Outcomes

Extractable and relevant to this review

  • Hypercalcaemia (serum calcium > 10.5 mg/dL (2.63 mmol/L))

  • Hyperphosphataemia (serum phosphorus > 7.0 mg/dL (2.26 mmol/L))

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • Nil

  • Stop or endpoint/s

    • NS

  • Additional data requested and/or received from authors

    • Methods (randomisation method, blinding, allocation concealment), end of treatment PTH, calcium, and phosphorus concentrations.

  • Completeness of follow‐up

    • Eligible/considered for inclusion: 204

    • Enrolled/randomised: 20

    • Analysed: 20

    • Per cent follow‐up: 100%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Blinding of participants, investigators, outcomes assessors and data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

High risk

Not performed

Was the study free of potential bias from the funding source?

High risk

Funded by a pharmaceutical company
Hayashi 2004

Methods

  • Setting/Design: Multicentre study

  • Time frame: NS

  • Follow‐up period: 12 months

  • Loss to follow‐up: 18/91 (20%)

Participants

  • Country: Japan

  • 18 years or older; HD twice or thrice weekly and met the following criteria:

    • iPTH = 150 pg/mL (16.5 pmol/L),

    • predialysis adjusted serum calcium = 10.5 mg/dL (2.63 mmol/L),

    • no history of treatment with vitamin D preparations or at least 4 week washout period,

    • on dialysis for at least 12 months and stable clinical findings,

    • absence of severe liver disease.

  • Exclusions: NS

Newer vitamin D group

  • Number: 38

  • Age:55.7 (13.6 SD) years

  • Sex (M/F):33/ 5

Established vitamin D group

  • Number:35

  • Age: 55.1 (11.2 SD) years

  • Sex (M/F): 25/10

Interventions

Newer vitamin D group

  • IV maxacalcitol: 10µg (for basal PTH > 500 pg/mL) or 5 µg (for basal iPTH < 500pg/mL) per dialysis session

Established vitamin D group

  • IV calcitriol: 1 µg/dialysis session

Cointerventions: Dialysate calcium, calcium carbonate

Outcomes

Extractable and relevant to this review

  • Fracture

  • Hypercalcaemia (adjusted calcium > 11.5 mg/dL (2.88 mmol/L))

  • Hyperphosphataemia (serum phosphorus > 6.0 mg/dL (1.9 mmol/L))

  • End of treatment serum calcium and phosphorus concentration

  • End of treatment iPTH concentration

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • NS

  • Additional data requested and/or received from authors

    • Methods (blinding), fracture and mortality events, end of treatment serum calcium, phosphorus, and PTH concentrations

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 203

    • Analysed: 176

    • Per cent follow‐up: 84%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Low risk

Sealed envelopes

Blinding?
All outcomes

Unclear risk

No blinding of participants, investigators, outcomes assessors or data assessors.

Intention‐to‐treat analysis ‐ was it performed?

High risk

Not performed

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Herrmann 1994

Methods

  • Setting/Design: 6 dialysis centres

  • Time frame: NS

  • Follow‐up period: 3 months

  • Loss to follow‐up: 84%

Participants

  • Country: Germany

  • HD; persistent elevation of 1‐84 iPTH (> 20 pmol/L) on 3 occasions; age > 16 years; normal vitamin D status; no corticosteroid or anticonvulsant treatment

  • Exclusions: Hypercalcaemia > 2.7 mmol/L (10.8 mg/dL) or hyperphosphataemia > 2.2 mmol/L (6.8 mg/dL) in three predialysis samples

Intermittent group

  • Number: 21

  • Age: 68.0 (range 25‐81) years

  • Sex (M/F): 10/11

Continuous group

  • Number: 24

  • Age: 64.5 (range 25‐80) years

  • Sex (M/F): 15/9

Interventions

Intermittent group

  • Oral calcitriol: At the end of the first (2.75 µg) and last (2.5 µg) dialysis session/ wk

Continuous group

  • Oral calcitriol: 0.75 µg/d

Cointerventions: Calcium carbonate, calcium acetate, aluminium hydroxide (one centre, protocol violation)

Outcomes

Extractable and relevant to this review

  • Hypercalcaemia (serum calcium > 10.8 mg/dL (2.7 mmol/L))

  • Hyperphosphataemia (serum phosphorus > 6.8 mg/dL (2.2 mmol/L) on 3 occasions)

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • Nil

  • Stop or endpoint/s

    • PTH < 91 pg/mL (10 pmol/L), serum calcium > 10.8 mg/dL (2.7 mmol/L) (single determination), or serum phosphorus 6.8 mg/dL (2.2 mmol/L) (3 determinations)

  • Additional data requested and/or received from authors

    • None

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 47

    • Analysed: 41

    • Per cent followed: 87%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Random number generation

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Blinding of participants, investigators, outcomes assessors or data assessors not stated

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not performed

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Indridason 2000

Methods

  • Setting/Design: 5 dialysis centres

  • Time frame: November 1994 to July 1996

  • Follow‐up period: 9 months

  • Loss to follow‐up: 19%

Participants

  • Country: USA

  • Patients initiating HD with a serum intact PTH between 150‐600 pg/mL

  • Exclusions: Dialysis duration >1 year; < 18 years; pregnancy; HIV disease; aluminium toxicity; prior parathyroidectomy; serum calcium > 10.5 mg/dL (2.63 mmol/L) without calcium or calcitriol therapy; vitamin D therapy within previous 2 months; treatment with steroids; phenytoin or phenobarbital; serious coexisting disease; plans for transplant or transfer to other dialysis modality; KT/V < 1.0 or urea reduction ratio < 55%.

IV group

  • Number: 19

  • Age: 53.3 (3.3 SD) years

  • Sex (M/F): 13/6

Oral group

  • Number: 20

  • Age: 54.6 (3.29 SD) years

  • Sex (M/F): 13/7

Calcium group

  • Number: 11

  • Age: 60.1 (3.36 SD) years

  • Sex (M/F): 3/8

Interventions

IV group

  • IV calcitriol: 1 µg/dialysis session (3 µg/wk) increased by 1.5 µg/wk titrated to serum calcium

Oral group

  • Oral calcitriol: 0.5 µg daily (3.5 µg/wk) increased 1.75 µg/wk titrated to serum calcium

Calcium group

  • Oral calcium carbonate: 2.5 g increased titrated to serum calcium

Cointerventions: Calcium carbonate, dietary advice, aluminium hydroxide

Outcomes

Extractable and relevant to this review

  • Hypercalcaemia (serum calcium > 10.5 mg/dL (2.63 mmol/L))

  • Hyperphosphataemia (serum phosphorus > 6.5 mg/dL (2.1 mmol/L))

  • End of treatment PTH concentration

  • End of treatment bone alkaline phosphatase concentration

  • End of treatment serum calcium and phosphorus concentration

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • Randomisation methods, death and fracture events, episodes of hypercalcaemia

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 52

    • Analysed: 42

    • Per cent followed: 81%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Permuted block randomisation

Allocation concealment?

Low risk

Adequate

Blinding?
All outcomes

Low risk

Blinding of outcome assessors.

Intention‐to‐treat analysis ‐ was it performed?

High risk

Not performed

Was the study free of potential bias from the funding source?

High risk

Funded by a pharmaceutical company
Jones 1994

Methods

  • Setting/Design: Single university centre, crossover study design

  • Time frame: 3 months

  • Follow‐up period: 3 months

  • Loss to follow‐up: 0%

Participants

  • Country: Canada

  • Paediatric study; CAPD or CCPD with an estimated GFR < 10 mL/min

  • Exclusions: NS

Oral group

  • Number: NS

  • Age: NS

  • Sex (M/F): NS

IP group

  • Number: NS

  • Age: NS

  • Sex (M/F): NS

Interventions

Oral group

  • Oral calcitriol: mean ± SD dose 8.4 ± 2.3 ng/kg/dose for 3 months

IP group

  • IP calcitriol: mean ± SD dose 7.3 ± 1.7 ng/kg/dose for 3 months

Cointerventions: Dietary phosphorus restriction, calcium carbonate, dialysate calcium concentration

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • Methods (randomisation, allocation concealment, blinding, and ITT analyses), deaths and fracture events, hypercalcaemia events, end of treatment serum calcium, and phosphorus (at end of first 3 months of treatment, prior to cross over)

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 7

    • Analysed: 7

    • Per cent follow‐up: 100%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stared

Blinding?
All outcomes

Low risk

Blinding of outcome assessors.

Intention‐to‐treat analysis ‐ was it performed?

Low risk

ITT performed

Was the study free of potential bias from the funding source?

Unclear risk

Funded by a pharmaceutical company
Khajehdehi 2003

Methods

  • Setting/Design: Single dialysis centre

  • Time frame: NS

  • Follow‐up period: 6 months

  • Loss to follow‐up: NS

Participants

  • Country: Iran

  • Adults requiring HD

  • Exclusions: NS

Established vitamin D group

  • Number: 32

  • Age: NS

  • Sex (M/F): NS

Placebo group

  • Number: 32

  • Age: NS

  • Sex (M/F): NS

Interventions

Established vitamin D group

  • Oral calcitriol: Twice weekly

Placebo group

  • Placebo

Cointerventions: Calcium carbonate 4.5 g/d

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • None

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 32

    • Analysed: NS

    • Per cent follow‐up: NS

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Not stated

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Kihara 2004

Methods

  • Setting/Design: Single dialysis centre

  • Time frame: 2001‐2003

  • Follow‐up period: 80 weeks

  • Loss to follow‐up: NS

Participants

  • Country: Japan

  • Intact PTH > 300 pg/mL (33 pmol/L); maintenance HD; corrected calcium < 10.5 mg/dL (2.63 mmol/L); phosphorus concentration < 6.5 mg/dL (2.1 mmol/L)

  • Exclusions: History of parathyroidectomy; kidney transplant; use of medications known to affect bone metabolism such as glucocorticoids, phenytoin, cyclosporine; diseases that affect bone metabolism such as malignancies; liver disease; gastrointestinal disease; tuberculosis; acquired immunodeficiency; chronic alcoholism; drug addiction; HD related amyloidosis

Newer vitamin D group

  • Number: NS

  • Age: NS

  • Sex (M/F): NS

Established vitamin D group

  • Number: NS

  • Age: NS

  • Sex (M/F): NS

Interventions

Newer vitamin D group

  • IV maxacalcitol: 0.5 µg thrice weekly

Established vitamin D group

  • IV calcitriol: 0.5 µg thrice weekly

Cointerventions: Calcium based phosphate binders

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • Nil

  • Stop or endpoint/s

    • NS

  • Additional data requested and/or received from authors

    • Methods (randomisation, allocation concealment, blinding)

  • Completeness of follow‐up

    • Eligible/considered for inclusion: 130

    • Enrolled/randomised:17

    • Analysed: NS

    • Per cent follow‐up: NS

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Not stated

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Klaus 1995

Methods

  • Setting/Design: University centre

  • Time frame: NS

  • Follow‐up period: NS

  • Loss to follow‐up: NS

Participants

  • Country: Germany

  • Dialysis dependent children

  • Exclusions: NS

Daily group

  • Number: 9

  • Age: NS

  • Sex (M/F): NS

Intermittent group

  • Number: 12

  • Age: NS

  • Sex (M/F): NS

Interventions

Daily group

  • Oral calcitriol: 0.5 µg/d

Intermittent group

  • Oral calcitriol: 1 µg thrice weekly

Cointerventions: Calcium‐containing phosphate binder

Outcomes

Extractable and relevant to this review

  • Hypercalcaemia (serum calcium > 11.2 mg/dL (2.8 mmol/L))

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • Treatment stopped if iPTH < 91 pg/mL (10 pmol/L), serum calcium > 11.2 mg/dL (2.8 mmol/L) or serum phosphorus > 7.7 mg/dL (2.5 mmol/L)

  • Additional data requested and/or received from authors

    • None

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 21

    • Analysed: NS

    • Per cent follow‐up: NS

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

High risk

No blinding of participants, investigators, outcome assessors or data assessors

Intention‐to‐treat analysis ‐ was it performed?

High risk

Not performed

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Koshikawa 2002

Methods

  • Setting/Design: Multicentre

  • Time frame: NS

  • Follow‐up period: 12 weeks

  • Loss to follow‐up: 52/151 (34%)

Participants

  • Country: Japan

  • Age 20‐75 years; PTH to conform to either (i) carboxy‐terminal > 5 ng/mL (ii) high‐sensitive mid‐terminal PTH > 20,000 pg/mL (iii) intact PTH > 150 pg/mL (16.5 pmol/L); predialysis adjusted calcium < 10 mg/dL (2.5 mg/dL); patients not receiving vitamin D preparations: stable clinical findings and dialysis > 3 months

  • Exclusions: Severe hepatic impairment; concurrent prescription of digitalis‐containing preparations; pregnant or lactating women

Established vitamin D group 1

  • Number: 43

  • Age: 50.0 (10.4 SD) years

  • Sex (M/F): 23/20

Established vitamin D group 2

  • Number: 44

  • Age: 51.4 (11.8 SD) years

  • Sex (M/F): 21/23

Established vitamin D group 3

  • Number: 43

  • Age: 51.0 (11.6 SD) years

  • Sex (M/F): 32/11

Placebo group

  • Number: 21

  • Age: 48.5 (12.5 SD) years

  • Sex (M/F): 12/9

Interventions

Established vitamin D group 1

  • IV calcitriol: 1 µg/dialysis

Established vitamin D group 2

  • IV calcitriol: 1.5 µg/dialysis

Established vitamin D group 3

  • IV calcitriol: 2 µg/dialysis

Placebo group

  • Placebo

Cointerventions: Calcium carbonate

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • Hypercalcaemia (serum calcium > 11.5 mg/dL (2.88 mmol/L)), patients included in safety analyses

  • Additional data requested and/or received from authors

    • Methods (randomisation method, allocation concealment), fracture, mortality, and hypercalcaemia events, end of treatment serum calcium, phosphorus, and PTH concentrations.

  • Completeness of follow‐up

    • Eligible/considered for inclusion: 162

    • Enrolled/randomised: 157

    • Analysed: 151

    • Per cent follow‐up: 99 (66%)

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Low risk

Blinding of participants, investigators, outcomes assessors and data assessors

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not performed

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Lee 1994

Methods

  • Setting/Design: Single dialysis centre, cross‐over study

  • Time frame: NS

  • Follow‐up period: 28 weeks

  • Loss to follow‐up: 0%

Participants

  • Country: New Zealand

  • maintenance HD with mild to moderate hyperparathyroidism (not defined)

  • Exclusions: Initial total serum calcium > 10.8 mg/dL (2.7 mmol/L); PTH < 90.1 pg/mL (10 pmol/L); phosphorus > 6.2mg/dL (2 mmol/L)

IV group

  • Number: 8

  • Age: NS

  • Sex (M/F): NS

Oral group

  • Number: 8

  • Age: NS

  • Sex (M/F): NS

Interventions

IV group

  • IV 1‐alpha‐hydroxyvitamin D3: 4 µg/thrice weekly for 6 weeks

Oral group

  • Oral 1‐alpha‐hydroxyvitamin D3: 4 µg/thrice weekly for 6 weeks

Cointerventions: All received aluminium hydroxide 1.2‐4.2 g/d and/or calcium carbonate 2.5‐11.25 g/d; use of phosphate binders was adjusted to maintain a predialysis plasma phosphate < 6.2 mg/dL

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • Nil

  • Stop or endpoint/s

    • NS

  • Additional data requested and/or received from authors

    • Methods (randomisation, allocation concealment, blinding, intention‐to treat analyses), episodes of hypercalcaemia or fracture, death, end of treatment serum calcium, phosphorus, and PTH, at the end of the first period of treatment.

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 16

    • Analysed: 16

    • Per cent follow‐up: 100%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

High risk

No blinding of participants, investigators, outcomes assessors or data assessors

Intention‐to‐treat analysis ‐ was it performed?

Low risk

ITT performed

Was the study free of potential bias from the funding source?

High risk

Funded by a pharmaceutical company
Levin 1995

Methods

  • Setting/Design: 5 centres

  • Time frame: NS

  • Follow‐up period: 6 months

  • Loss to follow‐up: 22/76 (29%)

Participants

  • Country: Canada

  • Medically stable paediatric patients (2‐18 years) undergone CCPD for at least. For those begun on dialysis due to AKI a period of 6 months stabilization was required before subjects became eligible, bone biopsy evidence of secondary hyperparathyroidism or normal rates of bone formation.

  • Exclusions: Other skeletal lesions of renal bone disease such as adynamic lesions, osteomalacia or mixed lesions; noncompliance with medication; undergone parathyroidectomy in previous 12 months; received prednisone or other immunosuppressive agents while undergoing regular dialysis.

IV group

  • Number: 16

  • Age: 12.5 (4.4 SD) years

  • Sex (M/F): 9/7

Oral group

  • Number: 17

  • Age: 13.2 (5.4 SD) years

  • Sex (M/F): 9/8

Interventions

IV group

  • IV calcitriol: 0.5 µg thrice weekly

Oral group

  • Oral calcitriol: 2 µg thrice weekly

Cointerventions: Calcium supplementation, standardised dialysate calcium

Outcomes

Extractable and relevant to this review

  • Suppression of iPTH concentration below 50% of baseline value

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • None

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 76

    • Analysed: 54

    • Per cent follow‐up: 71%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Not stated

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

High risk

Funded by pharmaceutical company
Levine 1996

Methods

  • Setting/Design: Single university centre/ open label RCT

  • Time frame: NS

  • Follow‐up period: 24 weeks

  • Loss to follow‐up: 3/18 (17%)

Participants

  • Country: USA

  • Plasma total calcium level < 9.5 mg/dL (2.4 mmol/L); serum PTH level > 200 pg/mL (22 pmol/L); HD three times/week; calcium x phosphorus product < 70 mg²/dL²; age 18‐70 years

  • Exclusions: NS

IV group

  • Number: 9

  • Age: 54.2 (10.3 SD) years

  • Sex (M/F): 9/0

Oral group

  • Number: 9

  • Age: 55.7 (13.1 SD) years

  • Sex (M/F): 9/0

Interventions

IV group

  • IV calcitriol: 2 µg/dialysis titrated to serum calcium to maximum 12 µg/wk

Oral group

  • Oral calcitriol: 2 µg/dialysis titrated to serum calcium to maximum 12 µg/wk

Cointerventions: Dialysate calcium adjustment, calcium and aluminium‐containing phosphate binders

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • Nil

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • Methods (randomisation, allocation concealment), number of deaths or fracture events during treatment, end of treatment serum phosphorus, calcium, and PTH concentrations.

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 18

    • Analysed: 15

    • Per cent follow‐up: 83%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

High risk

No blinding of participants, investigators, outcome assessors or data assessors

Intention‐to‐treat analysis ‐ was it performed?

High risk

Not performed

Was the study free of potential bias from the funding source?

High risk

Funded by a pharmaceutical company
Liou 1994

Methods

  • Setting/Design: Crossover study design

  • Time frame: NS

  • Follow‐up period: 12 weeks

  • Loss to follow‐up: 0%

Participants

  • Country: Taiwan

  • Maintenance HD who had at least a ten‐fold elevation of serum intact PTH and radiographic and/or histological evidence of secondary hyperparathyroidism

  • Exclusions: Use of vitamin D within 3 months prior to the study and use of anticonvulsants, steroids or other medications that may interfere with mineral metabolism

Intermittent group

  • Number: 5

  • Age: NS

  • Sex (M/F): NS

Daily group

  • Number: 5

  • Age: NS

  • Sex (M/F): NS

Interventions

Intermittent group

  • IV calcitriol: 0.5 µg thrice weekly

Daily group

  • Calcitriol: 0.25 µg/d increased in increments to a maximum 1.5 µg/d

Cointerventions: Aluminium‐containing phosphate binders

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • Nil

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • Methods (randomisation, allocation concealment, blinding, ITT), fracture or mortality events, end of treatment serum phosphorus, calcium, PTH concentrations, and episodes of hypercalcaemia

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 10

    • Analysed: 10

    • Per cent follow‐up: 100%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Not stated

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

High risk

Funded by a pharmaceutical company
Liou 1995

Methods

  • Setting/Design: Crossover study design

  • Time frame: NS

  • Follow‐up period: 8 weeks

  • Loss to follow‐up: NS

Participants

  • Country: Taiwan

  • Patients receiving CAPD with secondary hyperparathyroidism (undefined)

  • Exclusions: NS

SC group

  • Number: NS

  • Age: NS

  • Sex (M/F): NS

Oral group

  • Number: NS

  • Age: NS

  • Sex (M/F): NS

Interventions

SC group

  • SC calcitriol: 2 µg thrice weekly

Oral group

  • Oral calcitriol: 2 µg thrice weekly

Cointerventions: NS

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • None

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 6

    • Analysed: NS

    • Per cent follow‐up: NS

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

High risk

No blinding of participants or investigators. Blinding of outcome assessors or data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

High risk

Funded by a pharmaceutical company
Llach 1998

Methods

  • Setting/Design: Multicentre multiple ascending dose study

  • Time frame: NS

  • Follow‐up period: 16 weeks

  • Loss to follow‐up: NS

Participants

  • Country: USA

  • At least 18 years of age and undergoing HD; moderate to severe hyperparathyroidism defined as iPTH concentration > 300 pg/mL (33 pmol/L)

  • Exclusions: Allergy to vitamin D compounds; malignancy; liver disease; drug or alcohol abuse; or were at risk for aluminium‐related bone disease

Newer vitamin D group

  • Number: 22

  • Age: 49 (15 SD) years

  • Sex (M/F): 12/10

Placebo group

  • Number: 13

  • Age: 51 (18 SD) years

  • Sex (M/F): 6/7

Interventions

Newer vitamin D group

  • IV paricalcitol: 0.04 µg/kg thrice weekly for weeks with each successive group receiving 0.08 µg/kg, 0.16 µg/kg, or 0.24 µg/kg after the previous group had demonstrated safety at the previous dose level Placebo group

Placebo group

  • IV Placebo thrice weekly

Cointerventions: NS

Outcomes

Extractable and relevant to this review

  • Development of bone pain

  • Hypercalcaemia (serum calcium > 11.5 mg/dL (2.88 mmol/L))

  • Withdrawal of treatment due to hypercalcaemia

  • Decrease in serum iPTH of at least 30% from maximum baseline

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • Nil

  • Stop or endpoint/s

    • Hypercalcaemia (serum calcium > 11.5 mg/dL (2.88 mmol/L)) (3 in paricalcitol group), elevated calcium x phosphorus product (> 70) (3 in paricalcitol group), adverse events (mild persistent rash (1 in paricalcitol group))

  • Additional data requested and/or received from authors

    • Methods (blinding, randomisation, allocation concealment, ITT analyses), mean end of treatment PTH, calcium, and phosphorus concentrations.

  • Completeness of follow‐up

    • Eligible/considered for inclusion: 71

    • Enrolled/randomised: 35

    • Analysed: 100%

    • Per cent follow‐up: 100%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Blinding of participants and investigators. Blinding of outcome assessors or data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

ITT performed

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Martin 1998

Methods

  • Setting/Design: 11 dialysis centres, dose‐escalating multicentre studies (pooled data from 3 identical studies)

  • Time frame: NS

  • Follow‐up period: 3 months

  • Loss to follow‐up: 49%

Participants

  • Country: USA

  • HD patients with intact PTH > 400 pg/mL (44 pmol/L), normalised serum calcium between 8.0 and 10.0 mg/dL (2.0 and 2.5 mmol/L) and calcium phosphorus product < 75 mg²/dL²

  • Exclusions: NS

Newer vitamin D group

  • Number: 40

  • Age: 54 (14 SD) years

  • Sex (M/F): 21/19

Placebo group

  • Number: 38

  • Age: 54 (16 SD) years

  • Sex (M/F): 121/9

Interventions

Newer vitamin D group

  • IV paricalcitol: 0.04 µg/kg thrice weekly titrated to plasma PTH, incremented by 0.04 µg/kg at 2 weekly intervals if decline in PTH less than 30% of baseline, calcium < 11.5mg/dL, and calcium phosphorus product < 75 mg²/dL². The dose of the drug was reduced by one level if PTH became less than 100 pg/mL (11 pmol/L) or if hypercalcaemia (serum calcium > 11.5 mg/dL (2.88 mmol/L)) occurred or an elevated calcium phosphate product occurred (< 75 mg²/dL²)

Placebo group

  • IV placebo thrice weekly

Cointerventions: Calcium carbonate and calcium acetate based phosphate binders

Outcomes

Extractable and relevant to this review

  • Fracture

  • Decrease in PTH by > 30% from baseline

  • End of treatment PTH concentration

  • End of treatment serum calcium concentration

  • End of treatment serum phosphorus concentration

  • End of treatment alkaline phosphatase concentration

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • Nil

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • Methods (randomisation, allocation concealment, blinding), events during follow‐up (fracture)

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 78

    • Analysed: 40

    • Per cent follow‐up: 51%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Computer randomisation

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Low risk

Blinding of participants, investigators, outcomes assessors and data assessors

Intention‐to‐treat analysis ‐ was it performed?

Low risk

ITT performed

Was the study free of potential bias from the funding source?

Unclear risk

Funded by Abbott Laboratories
Martin 2001

Methods

  • Setting/Design: Multicentre

  • Time frame: NS

  • Follow‐up period: 12 weeks

  • Loss to follow‐up: 0%

Participants

  • Country: USA

  • Age ≥ 18 years; on maintenance dialysis therapy for at least one month; non‐pregnant and non lactating and use appropriate birth control; PTH level > 300 pg/mL (33 pmol/L); calcium level of 8.0‐10.5 mg/dL (2.0‐2.63 mmol/L) and calcium x phosphorus product < 70 mg²/dL²

  • Exclusions: Allergic reaction to calcitriol, paricalcitol injection or other vitamin D compounds; patients who required calcitonin, maintenance or oral or IV glucocorticoids therapy or other drugs that could affect bone metabolism throughout the entire study (other than women on stable oestrogen or progestin therapy) and patients who required the chronic use of phosphate binders containing aluminium; active malignancy; significant liver disease

Newer vitamin D group 1

  • Number: 64

  • Age: 56.1 (14.2 SD) years

  • Sex (M/F): 36/28

Newer vitamin D group 2

  • Number: 61

  • Age: 55.2 (13.6 SD) years

  • Sex (M/F): 29/32

Interventions

Newer vitamin D group 1

  • High dose IV paricalcitol: (baseline intact PTH/80) thrice weekly IV and placebo

Newer vitamin D group 2

  • Low dose IV paricalcitol: (dry weight x 0.04 µg) thrice weekly IV and placebo

Cointerventions: Calcium and aluminium containing phosphate binders

Outcomes

Extractable and relevant to this review

  • Four consecutive ≥ 30% reductions from baseline PTH levels

  • Raised calcium x phosphorus product (> 75 mg²/dL²)

  • Hypercalcaemia (calcium >11.5 mg/dL (2.88 mmol/L))

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • Nil

  • Stop or endpoint/s

    • Achievement of four consecutive decreases of ≥ 30% from baseline PTH level, experienced a single episode of hypercalcaemia (calcium > 11.5 mg/dL (2.88 mmol/L), or completed a maximum of 12 weeks of study procedures.

  • Additional data requested and/or received from authors

    • Methods (randomisation, allocation concealment, blinding), events (fractures), end of treatment serum concentrations (calcium, phosphorus, PTH)

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 125

    • Analysed: 125

    • Per cent follow‐up: 0%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Low risk

Blinding of participants, investigators, outcomes assessors and data assessors

Intention‐to‐treat analysis ‐ was it performed?

Low risk

ITT performed

Was the study free of potential bias from the funding source?

High risk

Funded by a pharmaceutical company
Martinez 1996

Methods

  • Setting/Design: NS

  • Time frame: NS

  • Follow‐up period: 12 weeks

  • Loss to follow‐up: 2/13 (15%)

Participants

  • Country: Spain

  • HD with iPTH > 400 pg/mL

  • Exclusions: NS

Once weekly group

  • Number: 6

  • Age: NS

  • Sex (M/F): NS

Thrice weekly group

  • Number: 7

  • Age: NS

  • Sex (M/F): NS

Interventions

Once weekly group

  • IV calcitriol: 6 µg once per week

Thrice weekly group

  • IV calcitriol: 2µg thrice weekly for 12 weeks

Cointerventions: Dialysate calcium, calcium‐containing phosphate binders

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • None

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised:13

    • Analysed: NS

    • Per cent follow‐up: NS

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Not stated

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Maxwell 1978

Methods

  • Setting/Design: Single university dialysis centre

  • Time frame: NS

  • Follow‐up period: 3 months

  • Loss to follow‐up: NS

Participants

  • Country: USA

  • Stable chronic HD patients; adult men or nonpregnant women; serum calcium level < 9.5 mg/dL (2.34 mmol/L) and fasting serum phosphorus value < 4.5 mg/dL (1.45 mmol/L)

  • Exclusions: NS

Established vitamin D group 1

  • Number: 13

  • Age: NS

  • Sex (M/F): NS

Established vitamin D group 2

  • Number: 9

  • Age: NS

  • Sex (M/F): NS

Interventions

Established vitamin D group 1

  • Oral calcitriol: 0.25‐1.5 µg/d

Established vitamin D group 2

  • Oral vitamin D3: 400 IU/d

Cointerventions: Aluminium hydroxide and calcium gluconate

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • Methods (randomisation, allocation concealment, blinding), events (fractures), end of treatment serum concentrations (phosphorus, calcium, PTH)

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 22

    • Analysed: NS

    • Percent follow‐up: NS

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Blinding of participants and investigators. Blinding of outcome assessors or data assessors not stated

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

High risk

Funded by a pharmaceutical company
Memmos 1981

Methods

  • Setting/Design: Single centre dialysis

  • Time frame: From April 1977

  • Follow‐up period: 24 months

  • Loss to follow‐up: 7/64 (11%) at one year, 32/64 (50%) at 2 years

Participants

  • Country: UK

  • Received dialysis treatment > one year

  • Exclusions: Plasma calcium > 12 mg/dL (3 mmol/L) or symptomatic hyperparathyroidism; had already received calcitriol or 1‐alpha‐hydroxyvitamin D3 or had had a parathyroidectomy

Established vitamin D group

  • Number: 27

  • Age: 50.1 (10.3 SD) years

  • Sex (M/F): 18/9

Placebo group

  • Number: 30

  • Age: 49.2 (11.2 SD) years

  • Sex (M/F): 19/11

Interventions

Established vitamin D group

  • Oral calcitriol: 0.5 µg/d

Placebo group

  • Placebo

Cointerventions: Aluminium hydroxide phosphate binders

Outcomes

Extractable and relevant to this review

  • All‐cause mortality

  • Development of bone pain

  • Development of periosteal erosions

  • Parathyroidectomy

  • End of treatment plasma PTH concentration

  • Need for parathyroidectomy

  • Loss of height

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • None stated

  • Stop or endpoint/s

    • Death (2 calcitriol, 1 placebo), transplantation (2 calcitriol), parathyroidectomy (2 placebo)

  • Additional data requested and/or received from authors

    • Methods (randomisation, blinding, allocation concealment), end of treatment serum values (calcium, phosphorus)

  • Completeness of follow‐up

    • Eligible/considered for inclusion: 127

    • Enrolled/randomised: 64

    • Analysed: 32 at 2 years

    • Per cent follow‐up: 50%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

By investigator (with no patient contact) allocated patients into 2 groups

Allocation concealment?

High risk

Inadequate

Blinding?
All outcomes

Low risk

Blinding of participants, investigators and outcomes assessors. Blinding of data assessors not stated

Intention‐to‐treat analysis ‐ was it performed?

High risk

ITT not performed

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Mitsopoulos 2006

Methods

  • Setting/Design: Single dialysis centre, dose comparison study

  • Time frame: NS

  • Follow‐up period: 12 weeks

  • Loss to follow‐up: 2/47 (5%) at 12 weeks

Participants

  • Country: Greece

  • Maintenance HD for at least 3 months with secondary hyperparathyroidism (iPTH level, 300 to 900 pg/mL (33‐99 pmol/L)); over 18 years; normal serum calcium (8.1‐10.4 mg/dL (2.1‐2.6 mmol/L)); Ca x P product < 70; off any vitamin metabolite replacement therapy for at least 1 month before enrolment; aluminium levels < 60 µg/L

  • Exclusions: Administration of calcitonin, bisphosphonates, or corticosteroids; presence of a clinically serious medical condition; previous parathyroidectomy; active malignancy.

Newer vitamin D group 1

  • Number: 22

  • Age: 61.5 (13.6 SD) years

  • Sex (M/F): 14/8

Newer vitamin D group 2

  • Number: 21

  • Age: 60.8 (11.2 SD) years

  • Sex (M/F): 14/7

Interventions

Newer vitamin D group 1

  • High dose IV paricalcitol: Initial dose baseline iPTH/80

Newer vitamin D group 2

  • Low dose IV paricalcitol: Initial dose baseline iPTH/120

Cointerventions: Dietary control of phosphorus, sevelamer hydrochloride, and calcium carbonate or aluminium hydroxide

Outcomes

Extractable and relevant to this review

  • All‐cause mortality

  • Hypercalcaemia (serum calcium > 10.4 mg/dL (2.59 mmol/L))

  • Reduction of iPTH > 30% from baseline value

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • Death (1 in PTH/80 dose group) and allergic reaction (1 in PTH/80 group)

  • Additional data requested and/or received from authors

    • Methods (randomisation, allocation concealment, blinding), end of treatment serum values (calcium, PTH, phosphorus)

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 47

    • Analysed: 47

    • Per cent follow‐up: 96%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

B ‐ Unclear

Blinding?
All outcomes

Unclear risk

Blinding of participants and investigators. Blinding of outcome assessors or data assessors not stated

Intention‐to‐treat analysis ‐ was it performed?

Low risk

ITT performed

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Mochizuki 2007

Methods

  • Setting/Design: Seventeen dialysis centres, crossover study design

  • Time frame: April 2002 to August 2003

  • Follow‐up period: 3 months

  • Loss to follow‐up: 11/31 (35%)

Participants

  • Country: Japan

  • Maintenance HD; any age; iPTH > 200 pg/mL; not received vitamin D injections for more than 3 months before enrolment.

  • Exclusions: Refused to participate; severe complications (unspecified) or concomitant conditions such as dementia.

Newer vitamin D group

  • Number: 14

  • Age: NS

  • Sex (M/F): 5/9

Established vitamin D group

  • Number: 17

  • Age: NS

  • Sex (M/F): 10/7

Interventions

Newer vitamin D group

  • IV maxacalcitol: Initial dose 10 µg/HD session for iPTH levels > 500 pg/mL, or 5 µg/HD session for iPTH levels < 500 pg/mL

Established vitamin D group

  • IV calcitriol: 1.0 µg/HD session adjusted within 0.5‐1.5 µg/HD session

Outcomes

Extractable and relevant to this review

  • Hypercalcaemia (serum calcium > 11.0 mg/dL (2.75 mmol/L))

  • Withdrawal of treatment due to hypercalcaemia (serum calcium > 11.0 mg/dL (2.75 mmol/L))

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • 6

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • Methods (allocation concealment, randomisation, blinding), end of treatment serum concentrations (calcium, phosphorus, PTH) for the first period of treatment

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 31

    • Analysed: 20

    • Per cent follow‐up: 65%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Not stated

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Moe 1998

Methods

  • Setting/Design: Two dialysis centres

  • Time frame: January 1993 to January 1995

  • Follow‐up period: 24 weeks

  • Loss to follow‐up: 3/21 (14%)

Participants

  • Country: USA

  • Age > 18 years; CAPD > 3 months; secondary hyperparathyroidism (intact PTH >200 pg/mL (22 pmol/L)) that was stable or rising since the start of CAPD together with an elevated serum total alkaline phosphatase concentration and/or radiographical evidence of bone resorption

  • Exclusions: Aluminium associated bone disease (desferrioxamine (DFO) stimulation test); serum calcium > 10 mg/dL or serum phosphorus >7.1 mg/dL, receiving medications known to interfere with vitamin D metabolism or bone turnover such as steroids or anticonvulsants; non‐compliant with dialysis prescription

Intermittent group

  • Number: 10

  • Age: 50.6 (15.9 SD) years

  • Sex (M/F): 5/5

Daily group

  • Number: 8

  • Age: 41.2 (17.8 SD) years

  • Sex (M/F): 4/4

Interventions

Intermittent group

  • Oral calcitriol: 3 µg twice weekly

Daily group
Oral calcitriol: 0.75 µg/d

Cointerventions: Low calcium dialysate, calcium acetate as phosphate binder. Calcium acetate to keep phosphorus < 6.0 mg/dL (1.94 mmol/L). Calcium carbonate if not tolerated.

Outcomes

Extractable and relevant to this review

  • Fracture

  • Hypercalcaemia (serum calcium > 11.6 mg/dL (2.9 mmol/L))

  • Hyperphosphataemia (serum phosphorus > 7.1 mg/dL (2.3 mmol/L))

  • End of treatment serum calcium, phosphorus, and PTH concentrations

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • None stated

  • Stop or endpoint/s

    • Transplantation (1 intermittent), unable to take medication (1 daily), non‐compliant (1 daily)

  • Additional data requested and/or received from authors

    • Methods (blinding, allocation concealment), events (fracture).

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 21

    • Analysed: 18

    • Per cent follow‐up: 86%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Random number generator

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

High risk

No blinding of participants, investigators, outcome assessors or data assessors

Intention‐to‐treat analysis ‐ was it performed?

High risk

ITT not performed

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Moe 2001

Methods

  • Setting/Design: Three area dialysis units, study of immunomodulatory effects of paricalcitol

  • Time frame: NS

  • Follow‐up period: 3 months

  • Loss to follow‐up: 6%

Participants

  • Country: USA

  • Age > 18 years; HD > 3 months, able to give informed consent; medically stable; serum intact PTH < 200 pg/mL; not on calcitriol or vitamin D therapy for at least 3 months; serum calcium < 10.5 mg/dL (2.63 mmol/L) in 80% of measurements in the last 6 months or last 3 consecutive measures obtained during a 2 week period after reducing the patients dialysis calcium bath calcium concentration or last 3 consecutive measures obtained during a 2‐week period after changing a patient from a calcium‐containing phosphate binder to sevelamer during the run‐in portion of the protocol; serum phosphorus level > 2.5 and < 7.0 mg/dL in 80% of measurements in the last 6 months, or a calcium phosphate product of ≤ 70 mg²/dL² in 80% of measures in the last 6 months; serum 1,25(OH2)D3 levels in the normal range and a HCT > 30%

  • Exclusions: Known active malignancy; liver disease (serum aspartate aminotransferase, alanine transferase, or gamma‐glutamyltransferase levels > 2 times the upper limits of normal)L; HIV or other known immune system disorder; history of more than 1 month of therapy with the daily ingestion of 90 mL or 3 tabs of aluminium hydroxide by history or chart review or an elevated aluminium level > 40 µg/L; pregnant or lactating women; or currently administered drugs known to suppress immune function such as corticosteroids

Newer vitamin D group

  • Number: 16

  • Age: 53.6 (11.4 SD) years

  • Sex (M/F): 12/4

Placebo group

  • Number: 15

  • Age: 53.0 ( 9.6 SD) years

  • Sex (M/F): 7/8

Interventions

Newer vitamin D group

  • IV paricalcitol: 1‐4 µg thrice weekly

Placebo group

  • Placebo

Cointerventions: Sevelamer hydrochloride and adjustment of dialysate calcium

Outcomes

Extractable and relevant to this review

  • All‐cause mortality

  • End of treatment PTH concentration

  • End of treatment alkaline phosphatase

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • 1

  • Stop or endpoint/s

    • Inability to tolerate paricalcitol

  • Additional data requested and/or received from authors

    • Methods (allocation concealment, blinding, randomisation methods), events (fracture), end of treatment serum values (calcium, phosphorus)

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 32

    • Analysed: 30

    • Per cent follow‐up: 94%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Blinding of participants and investigators. Blinding of outcome assessors or data assessors not stated

Intention‐to‐treat analysis ‐ was it performed?

High risk

Not performed

Was the study free of potential bias from the funding source?

High risk

Funded by a pharmaceutical company
Moriniere 1985

Methods

  • Setting/Design: Single centre

  • Time frame: NS

  • Follow‐up period: 6 months

  • Loss to follow‐up: 0%

Participants

  • Country: France

  • Reliable patients on HD; plasma calcium (9.5 mg/dL (2.4 mmol/L)) and phosphorus (5.0 mg/dL (1.6 mmol/L)) well controlled with calcium carbonate alone

  • Exclusions: NS

Established vitamin D group

  • Number: 12

  • Age: NS

  • Sex (M/F): NS

No treatment group

  • Number: 15

  • Age: NS

  • Sex (M/F): NS

Interventions

Established vitamin D group

  • Oral 1‐alpha‐hydroxyvitamin D3: 1 µg/d

No treatment group

  • No treatment

Cointerventions: Calcium carbonate, aluminium hydroxide

Outcomes

Extractable and relevant to this review

  • Development of bone pain

  • Development of vascular calcification

  • End of treatment serum calcium, phosphorus, PTH, and alkaline phosphatase

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • None stated

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • Methods (allocation concealment, randomisation, blinding), events (fracture)

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 27

    • Analysed: 27

    • Per cent follow‐up: 100%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Random number generator

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Low risk

Blinding of participants, outcomes assessors and data assessors, but not investigators

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

ITT performed

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Pecovnik‐Balon 1995

Methods

  • Setting/Design: Three dialysis centres

  • Time frame: NS

  • Follow‐up period: 12 months

  • Loss to follow‐up: NS

Participants

  • Country: Slovenia

  • Chronic HD

  • Exclusions: NS

Established vitamin D group

  • Number: 31

  • Age: NS

  • Sex (M/F): 19/13

No treatment group

  • Number: 26

  • Age: NS

  • Sex (M/F): 12/14

Interventions

Established vitamin D group

  • Oral calcitriol: 0.25 µg/d

No treatment group

  • No treatment

Cointerventions: Dietary advice, calcium carbonate or aluminium hydroxide

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • None stated

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • Methods (allocation concealment, randomisation, blinding, ITT analysis), events (fracture, deaths), end of treatment serum concentrations (calcium, phosphorus, PTH)

  • Completeness of follow‐up

    • Eligible/considered for inclusion: 93

    • Enrolled/randomised: 57

    • Analysed: NS

    • Per cent follow‐up: NS

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Not stated

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Popovtzer 1992

Methods

  • Setting/Design: Seven Israeli dialysis units

  • Time frame: NS

  • Follow‐up period: 16 months

  • Loss to follow‐up: 15/56 (27%) (29/56 bone histomorphometry)

Participants

  • Country: Israel

  • Maintenance HD > 3 months

  • Exclusions: Malignancy; mental illness; current treatments that might affect bone, calcium, or vitamin D metabolism, such as corticosteroid or anticonvulsant administration, or parathyroidectomy

Established vitamin D group 1

  • Number: 19

  • Age: 45.7 (12.7 SD) years

  • Sex (M/F): 10/9

Established vitamin D group 2

  • Number: 22

  • Age: 49.5 (12.4 SD) years

  • Sex (M/F): 13/9

Interventions

Established vitamin D group 1

  • Oral 1‐alpha‐hydroxyvitamin D3: 0.25‐1 µg/d

Established vitamin D group 2

  • Oral 24,25 dihydroxyvitamin D3: 5 µg twice daily

  • Oral 1‐alpha‐hydroxyvitamin D3: 0.25‐1 µg/d

Cointerventions: Aluminium hydroxide as phosphate binders + oral calcium gluconate supplements

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • None stated

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • None

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 56

    • Analysed: 31

    • Per cent follow‐up: 55%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Blinding of participants, investigators or outcome assessors not stated. Data assessors were blinded.

Intention‐to‐treat analysis ‐ was it performed?

High risk

Not performed

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Qiu 2003

Methods

  • Setting/Design: Multicentre study, double‐blind placebo controlled

  • Time frame: NS

  • Follow‐up period: 12 weeks

  • Loss to follow‐up: 4/74 (5%)

Participants

  • Country: USA

  • Adults requiring CAPD or CCPD

  • Exclusions: NS

Newer vitamin D group

  • Number: 36

  • Age: NS

  • Sex (M/F): NS

Placebo group

  • Number: 35

  • Age: NS

  • Sex (M/F): NS

Interventions

Newer vitamin D group

  • Oral paricalcitol: Initial µg dose iPTH/60

Placebo group

  • Placebo

Cointerventions: NS

Outcomes

Extractable and relevant to this review

  • Two consecutive decreases of iPTH > 30% below baseline

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • Two consecutive ≥ 30% decreases in iPTH from baseline

  • Additional data requested and/or received from authors

    • None

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 74

    • Analysed: 70

    • Per cent follow‐up: 95%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Blinding of participants and investigators. Blinding of outcome assessors or data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

High risk

Not performed

Was the study free of potential bias from the funding source?

High risk

Funded by Abbott Laboratories
Quarles 1994

Methods

  • Setting/Design: Multicentre university study (4 centres)

  • Time frame: NS

  • Follow‐up period: 9 months

  • Loss to follow‐up: Adverse events 0%

Participants

  • Country: USA

  • Age 18‐65 years; thrice weekly HD; iPTH 250‐2500 pg/mL (28.5‐285 pmol/L)

  • Exclusions: Prior treatment with calcitriol or other vitamin D analogues in doses exceeding 0.5 µg/d; type I diabetes mellitus; prior parathyroidectomy, unsuccessful kidney transplant within one year; iron overload as defined by random serum ferritin > 1000 ng/mL; treatment in the last 6 months with medications such as phenobarbital, diphenylhydantoin or glucocorticoid which may interfere with vitamin D and/or bone homeostasis; inadequate dialysis as evidenced by predialysis BUN > 120 mg/dL; total calcium > 10.5 mg/dL (2.62 mmol/L) and serum phosphorus > 7.0 mg/dL (2.24) or serum aluminium > 100 µg/L

IV group

  • Number: 10

  • Age: 39.2 (12.6 SD) years

  • Sex (M/F): 4/6

Oral group

  • Number: 9

  • Age: 41 (9.3 SD) years

  • Sex (M/F): 2/7

Interventions

IV group

  • IV calcitriol: 2‐4 µg thrice weekly titrated to serum calcium 10.2‐10.5 mg/dL (2.55‐2.63 mmol/L)

Oral group

  • Oral calcitriol: 2‐4µg thrice weekly titrated to serum calcium 10.2‐10.5 mg/dL (2.55‐2.63 mmol/L)

Cointerventions: Dietary calcium and phosphate restriction, calcium carbonate and aluminium containing phosphate binders

Outcomes

Extractable and relevant to this review

  • Hypercalcaemia (serum calcium >10.5 mg/dL (2.63 mmol/L))

  • Hyperphosphataemia (serum phosphorus >7.0 mg/dL (2.3 mmol/L))

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • None stated

  • Stop or endpoint/s

    • Transplantation (1 IV group), change to PD (1 oral group)

  • Additional data requested and/or received from authors

    • Methods (ITT analysis), events (fractures), end of treatment serum concentrations (calcium, phosphorus, PTH)

  • Completeness of follow‐up

    • Eligible/considered for inclusion: 257

    • Enrolled/randomised: 23/19

    • Analysed:19

    • Per cent follow‐up: 100%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Table of random numbers, following pairing according to PTH concentration

Allocation concealment?

Low risk

Adequate

Blinding?
All outcomes

Low risk

Blinding of participants, investigators and outcomes assessors. Blinding of data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

High risk

Not performed

Was the study free of potential bias from the funding source?

High risk

Funded by pharmaceutical company
Salusky 1998

Methods

  • Setting/Design: Single dialysis centre

  • Time frame: NS

  • Follow‐up period: 12 months

  • Loss to follow‐up: 0%

Participants

  • Country: USA

  • Medically stable paediatric patients on CCPD for at least 2 months; age 2‐18 years. For those begun on dialysis due to AKI a period of 6 months stabilisation was required before subjects became eligible; bone biopsy evidence of secondary hyperparathyroidism or normal rates of bone formation.

  • Exclusions: Other skeletal lesions of renal bone disease such as adynamic lesions, osteomalacia or mixed lesions; noncompliance with medication; parathyroidectomy in previous 12 months; received prednisone or other immunosuppressive agents while undergoing regular dialysis.

IP group

  • Number: 16

  • Age: 12.5 (4.4 SD) years

  • Sex (M/F): 9/7

Oral group

  • Number: 17

  • Age: 13.2 (5.4 SD) years

  • Sex (M/F): 9/8

Interventions

IP group

  • IP calcitriol: 1 µg/d titrated to serum calcium < 10.5 mg/dL (2.63 mmol/L) and phosphorus < 6.0 mg/dL (1.94 mmol/L)

Oral group

  • Oral calcitriol: 1 µg/d titrated to serum calcium < 10.5 mg/dL (2.63 mmol/L) and phosphorus < 6.0 mg/dL (1.94 mmol/L)

Cointerventions: Calcium carbonate, dietary modification, dialysate modification, aluminium‐containing phosphate binders

Outcomes

Extractable and relevant to this review

  • Hypercalcaemia (serum calcium > 11.0 mg/dL (2.75 mmol/L))

  • Hyperphosphataemia (serum phosphorus > 7.0 mg/dL (2.26 mmol/L))

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • None stated

  • Stop or endpoint/s

    • Persistent serum calcium > 11.0 mg/dL despite reduction of calcitriol dose, reduction of dialysate calcium content, and switch from calcium containing to aluminium containing phosphate binding agents

  • Additional data requested and/or received from authors

    • Methods (allocation concealment, blinding, randomisation method, ITT analyses), events (death or fractures), end of treatment serum calcium, phosphorus, PTH)

  • Completeness of follow‐up

    • Eligible/considered for inclusion: 46

    • Enrolled/randomised: 33

    • Analysed: 33

    • Per cent follow‐up: 100%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Low risk

Biostatistician using 3 randomisation schedules, one for each skeletal lesion, that is, osteitis fibrosa, secondary hyperparathyroidism and normal bone formation.

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

High risk

No blinding of participants or investigators. Blinding of outcome assessors or data assessors not stated

Intention‐to‐treat analysis ‐ was it performed?

High risk

ITT not performed

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Sanchez Perales 1999

Methods

  • Setting/Design: Single centre

  • Time frame: NS

  • Follow‐up period: 3 months

  • Loss to follow‐up: 0%

Participants

  • Country: Spain

  • HD patients with biochemical hyperparathyroidism

  • Exclusions: NS

Weekly group

  • Number: 11

  • Age: 52.9 (16 SD) years

  • Sex (M/F): 5/6

Thrice weekly group

  • Number: 11

  • Age 48.4 (20 SD) years

  • Sex (M/F): 6/5

Interventions

Weekly group

  • IV calcitriol: 3 µg/wk

Thrice weekly group

  • IV calcitriol: 1 µg 3 times/wk

Cointerventions: Calcium carbonate and aluminium‐containing phosphate binders

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • None

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 22

    • Analysed: 22

    • Per cent follow‐up: 100%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Not stated

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Sprague 2003

Methods

  • Setting/Design: Multicentre (27 centres)

  • Time frame: 1995 to 1996

  • Follow‐up period: Up to 8 months

  • Loss to follow‐up: 29/266 (11%)

Participants

  • Country: USA

  • Medically stable patients undergoing chronic HD three times/week for at least 6 months who had not previously enrolled in a paricalcitol study

  • Exclusions: Screening PTH value > 250 pg/mL (28.5 pmol/L) or 300 pg/mL (33 pmol/L) if naive to vitamin D therapy; screening calcium value > 11.5 mg/dL (2.63 mmol/L); screening Ca X P > 70 mg²/dL²; history of significant allergy to calcitriol or other vitamin D compounds; necessity for calcitonin; maintenance oral or IV glucocorticoids or other drugs that could have affected calcium or bone metabolism other than females or stable oestrogen or progestin therapy

Newer vitamin D group

  • Number: 130

  • Age: 56.7 (15.5 SD) years

  • Sex (M/F): 70/60

Established vitamin D group

  • Number: 133

  • Age: 56.6 (14.3 SD) years

  • Sex (M/F): 80/53

Interventions

Newer vitamin D group

  • IV paricalcitol: 0.04‐0.24 µg/kg/thrice weekly

Established vitamin D group

  • IV calcitriol: 0.01‐0.06 µg/kg/thrice weekly

Cointerventions: Phosphate binders using calcium carbonate or calcium acetate

Outcomes

Extractable and relevant to this review

  • Reduction in PTH concentration > 50%

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • None stated

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • Methods (allocation concealment, randomisation, blinding), events (fractures, deaths, complete follow‐up, hypercalcaemia), end of treatment serum concentrations (calcium, phosphorus, PTH)

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 266

    • Analysed: 237

    • Per cent follow‐up: 89%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Blinding of participants and investigators. Blinding of outcome assessors or data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

Low risk

ITT performed

Was the study free of potential bias from the funding source?

High risk

Funded by Abbott Laboratories
Tarrass 2006

Methods

  • Setting/Design: Single university centre

  • Time frame: NS

  • Follow‐up period: 12 weeks

  • Loss to follow‐up: 0%

Participants

  • Country: Morocco

  • HD patients with basal iPTH over 4 times the normal upper limit. All patients had plasma aluminium levels < 50 µg/L.

  • Exclusions: NS

Intermittent group

  • Number: 18

  • Age: 47.16 (15.11 SD) years

  • Sex (M/F): 5/13

Continuous group

  • Number: 16

  • Age: 46.64 (14.6 SD) years

  • Sex (M/F): 6/10

Interventions

Intermittent group

  • Oral alfacalcidol: 2 µg/dialysis session, thrice weekly

Continuous group

  • Oral alfacalcidol: 1 µg 6 days/wk

Cointerventions: Calcium carbonate

Outcomes

Extractable and relevant to this review

  • Hypercalcaemia (serum calcium > 10.5 mg/dL (2.63 mmol/L))

  • Hyperphosphataemia (serum phosphorus > 7mg/dL (2.26 mmol/L))

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • NS

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • Methods (randomisation, allocation concealment, blinding) end of treatment serum concentrations (calcium, phosphorus, PTH)

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 34

    • Analysed: 34

    • Per cent follow‐up: 100%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Not stated

Intention‐to‐treat analysis ‐ was it performed?

Low risk

ITT performed

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Tsuruoka 2003

Methods

  • Setting/Design: Single centre, crossover design

  • Time frame: NS

  • Follow‐up period: 12 months

  • Loss to follow‐up: 3/13 (23%)

Participants

  • Country: Japan

  • HD patients

  • Exclusions: NS

Morning group

  • Number: NS

  • Age: NS

  • Sex (M/F): NS

Evening group

  • Number: NS

  • Age: NS

  • Sex (M/F): NS

Interventions

Morning group

  • Oral vitamin D3: 3 µg thrice weekly 08:00

Evening group

  • Oral vitamin D3: 3 µg thrice weekly 20:00

Cointerventions: NS

Outcomes

Extractable relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • None stated

  • Stop or endpoint/s

    • None stated

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 13

    • Analysed: 10

    • Per cent follow‐up: 77%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

High risk

No blinding of participants, investigators, outcome assessors or data assessors.

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Turk 2002

Methods

  • Setting/Design: Two centres

  • Time frame: NS

  • Follow‐up period: 6 months

  • Loss to follow‐up: 1/28 (3.6%)

Participants

  • Country: Turkey

  • HD patients with secondary hyperparathyroidism

  • Exclusions: NS

Oral group

  • Number: 14

  • Age: 42 (15 SD) years

  • Sex (M/F): 7/7

IV group

  • Number: 14

  • Age: 38 (14 SD) years

  • Sex (M/F): 6/8

Interventions

Oral group

  • Oral calcitriol: 1‐3 µg thrice weekly

IV group

  • IV calcitriol: 1‐3 µg thrice weekly

Cointerventions: Calcium acetate and aluminium salts

Outcomes

Extractable and relevant to this review

  • All‐cause mortality

  • End of treatment serum calcium, phosphorus, iPTH, alkaline phosphatase concentration

  • End of treatment bone mineral density (femoral neck and lumbar spine)

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • Nil

  • Stop or endpoint/s

    • None stated

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 28

    • Analysed: 27

    • Per cent follow‐up: 96%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

High risk

Alternating

Allocation concealment?

High risk

Inadequate

Blinding?
All outcomes

Unclear risk

Not stated

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
van der Merwe 1990

Methods

  • Setting/Design: Single hospital HD centre

  • Time frame: NS

  • Follow‐up period: 12 weeks

  • Loss to follow‐up: 3/19 (16%)

Participants

  • Country: Scotland

  • HD patients with biochemical evidence of hyperparathyroidism

  • Exclusions: NS

Daily group

  • Number: 9

  • Age: NS

  • Sex (M/F): NS

Intermittent group

  • Number: 10

  • Age: NS

  • Sex (M/F): NS

Interventions

Daily group

  • Oral calcitriol: 0.25‐3 µg/d titrated with increasing doses until serum calcium 10.4‐10.8 mg/dL (2.1‐2.2 mmol/L)

Intermittent group

  • Oral calcitriol: 0.5‐4 µg thrice weekly with increasing doses until serum calcium 10.4‐10.8 mg/dL (2.1‐2.2 mmol/L)

Cointerventions: NS

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • Nil

  • Stop or endpoint/s

    • Intolerance of medication (1 in intermittent group), transplantation (1 patient, unreported treatment assignment), urological surgery (1 patient, unreported treatment assignment)

  • Additional data requested and/or received from authors

    • Methods (randomisation, allocation concealment, blinding, ITT analysis), events (death, fracture, hypercalcaemia), end of treatment serum concentrations (calcium, phosphorus, PTH)

  • Completeness of follow‐up

    • Eligible/considered for inclusion: 71

    • Enrolled/randomised: 35

    • Analysed: 35

    • Per cent follow‐up: 100%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

High risk

No blinding of participants or investigators. Blinding of outcome assessors or data assessors not stated.

Intention‐to‐treat analysis ‐ was it performed?

Low risk

ITT performed

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Varghese 1992

Methods

  • Setting/Design: Single centre crossover study

  • Time frame: NS

  • Follow‐up period: 3 months

  • Loss to follow‐up: 0%

Participants

  • Country: UK

  • Chronic HD patients

  • Exclusions: NS

Established vitamin D group

  • Number: NS

  • Age: NS

  • Sex (M/F): NS

Placebo

  • Number: NS

  • Age: NS

  • Sex (M/F): NS

Overall

  • Number: 12

  • Age range: 27‐69 years

  • Sex (M/F): 6/6

Interventions

Established vitamin D group

  • Oral 24,25(OH)2D3: 10 µg/d

Placebo group

  • Placebo

Cointerventions: Phosphate binding antacids

Outcomes

Extractable and relevant to this review

  • Nil

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • Nil

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • Methods (randomisation, allocation concealment, blinding, ITT), events (fracture), end of treatment serum calcium, phosphorus, PTH)

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 12

    • Analysed: 12

    • Per cent follow‐up: 100%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Alternating envelopes

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

Unclear risk

Not stated

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

Unclear risk

Funding source not stated
Watson 1989

Methods

  • Setting/Design: University study

  • Time frame: NS

  • Follow‐up period: 6 months

  • Loss to follow‐up: 0%

Participants

  • Country: Canada

  • Paediatric patients requiring CAPD; no evidence on clinical or radiological grounds of bone disease (i.e. less than severe erosions on plain film)

  • Exclusions: NS

Established vitamin D group

  • Number: 6

  • Age: 11.5 (6 SD) years

  • Sex (M/F): 4/2

No treatment group

  • Number: 6

  • Age: 10.1 (6.9 SD) years

  • Sex (M/F): 4/2

Interventions

Established vitamin D group

  • Oral 1‐alpha‐hydroxyvitamin D3: 10‐20 ng/kg/d

No treatment group

  • No treatment

Cointerventions: Restriction of dietary phosphorus, cholecalciferol 400 IU/d, calcium carbonate, vitamin B and C, aluminium hydroxide

Outcomes

Extractable and relevant to this review

  • Fracture at any site

  • Hypercalcaemia (undefined)

  • Hyperphosphataemia (undefined)

  • Withdrawal of treatment due to hypercalcaemia

  • End of treatment PTH concentration

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • Nil

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • Methods (blinding), events (fractures, hypercalcaemia), end of treatment serum phosphorus and calcium concentrations

  • Completeness of follow‐up

    • Eligible/considered for inclusion: NS

    • Enrolled/randomised: 12

    • Analysed: 12

    • Per cent follow‐up: 100%

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Low risk

Adequate (sealed envelopes)

Blinding?
All outcomes

Low risk

No blinding of participant or investigators. Outcomes assessors and data assessors were blinded.

Intention‐to‐treat analysis ‐ was it performed?

Low risk

ITT performed

Was the study free of potential bias from the funding source?

High risk

Funded by Abbott Laboratories
Zisman 2005

Methods

  • Setting/Design: Phase IV open‐label single‐centre study

  • Time frame: NS

  • Follow‐up period: 1.5 months

  • Loss to follow‐up: NS

Participants

  • Country: USA

  • Medically stable adult patients receiving chronic HD 2‐3 times weekly for at least 6 months and who had been treated with a stable dose of paricalcitol for at least 6 months

  • Exclusions: Serum calcium > 10.5 mg/dL (2.63 mmol/L), phosphorus > 8mg/dL (2.6 mmol/L), Ca x P > 70 mg²/dL²

Low dose group

  • Number: 9

  • Age: 56 (15.3 SD) years

  • Sex (M/F): 6/3

Intermediate dose group

  • Number: 8

  • Age: 57 (15.6 SD) years

  • Sex (M/F): 6/2

High dose group

  • Number: 10

  • Age: 54 (10.9 SD) years

  • Sex (M/F): 7/3

Interventions

Low dose group

  • IV doxercalciferol: 35% of previous paricalcitol dose, thrice weekly

Intermediate dose group

  • IV doxercalciferol: 50% of previous paricalcitol dose, thrice weekly

High dose group

  • IV doxercalciferol: 65% of previous paricalcitol dose, thrice weekly

Cointerventions: Phosphate binders, dietary phosphorus restriction

Outcomes

Extractable and relevant to this review

  • End of treatment serum calcium, PTH, phosphorus concentrations

Notes

  • Exclusions post‐randomisation but pre‐intervention

    • Nil

  • Stop or endpoint/s

    • None stated

  • Additional data requested and/or received from authors

    • None

  • Completeness of follow‐up

    • Eligible/considered for inclusion: 46

    • Enrolled/randomised: 27

    • Analysed: NS

    • Per cent follow‐up: NS

Risk of bias

Bias

Authors' judgement

Support for judgement

Adequate sequence generation?

Unclear risk

Not stated

Allocation concealment?

Unclear risk

Not stated

Blinding?
All outcomes

High risk

No blinding of participants, investigators, outcome assessors or data assessors.

Intention‐to‐treat analysis ‐ was it performed?

Unclear risk

Not stated

Was the study free of potential bias from the funding source?

High risk

Funded by pharmaceutical company

AKI ‐ acute kidney injury; CAPD ‐ continuous ambulatory peritoneal dialysis; CCPD ‐ continuous cyclic peritoneal dialysis; GFR ‐ glomerular filtration rate; HCT ‐ haematocrit; HD ‐ haemodialysis; IP ‐ intraperitoneal; IV‐ intravenous; NS ‐ not stated; PD ‐ peritoneal dialysis; SC‐ subcutaneous

Characteristics of ongoing studies [ordered by study ID]

Ir a:

NCT00257920

Trial name or title

A study to evaluate the effects of two vitamin D analogs, Zemplar injection and Hectorol injection, on intestinal absorption of calcium in patients with Stage 5 CKD

Methods

Participants

Stage 5 CKD patients on HD three times a week for at least 2 months, iPTH level > 200 pg/mL

Interventions

Zemplar injection versus Hectorol injection

Outcomes

Intestinal calcium absorption

Starting date

May 2006

Contact information

[email protected]

Notes
NCT00397475

Trial name or title

Evaluation of colecalciferol substitution in dialysis patients

Methods

Participants

Dialysis patients, vitamin D levels < 60 ng/mL

Interventions

Colecalciferol versus placebo

Outcomes

Bone metabolism and immune system

Starting date

November 2006

Contact information

Eric Seibert, MD
drericseibert@gmx‐topmail.de

Notes

Data and analyses

Open in table viewer
Comparison 1. Vitamin D compounds versus placebo/no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

5

233

Risk Ratio (M‐H, Random, 95% CI)

1.34 [0.34, 5.24]
Analysis 1.1
Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 1 All‐cause mortality.

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 1 All‐cause mortality.

1.1 Established vitamin D compounds

3

168

Risk Ratio (M‐H, Random, 95% CI)

1.11 [0.24, 5.05]

1.2 Newer vitamin D compounds

2

65

Risk Ratio (M‐H, Random, 95% CI)

3.00 [0.13, 68.26]

2 Fracture Show forest plot

4

181

Risk Ratio (M‐H, Random, 95% CI)

1.0 [0.06, 15.41]
Analysis 1.2
Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 2 Fracture.

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 2 Fracture.

2.1 Established vitamin D compounds

3

103

Risk Ratio (M‐H, Random, 95% CI)

1.0 [0.06, 15.41]

2.2 Newer vitamin D compounds

1

78

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3 Development of bone pain Show forest plot

4

109

Risk Ratio (M‐H, Random, 95% CI)

0.29 [0.03, 2.63]
Analysis 1.3
Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 3 Development of bone pain.

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 3 Development of bone pain.

3.1 Established vitamin D compounds

3

74

Risk Ratio (M‐H, Random, 95% CI)

0.41 [0.02, 9.25]

3.2 Newer vitamin D compounds

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.20 [0.01, 4.65]

4 Parathyroidectomy Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only
Analysis 1.4
Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 4 Parathyroidectomy.

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 4 Parathyroidectomy.

4.1 Established vitamin D compounds

2

133

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.05, 12.47]

4.2 Newer vitamin D compounds

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5 Development of subperiosteal erosions Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only
Analysis 1.5
Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 5 Development of subperiosteal erosions.

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 5 Development of subperiosteal erosions.

5.1 Established vitamin D compounds

3

120

Risk Ratio (M‐H, Random, 95% CI)

0.41 [0.07, 2.38]

5.2 Newer vitamin D compounds

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6 Resolution of subperiosteal erosions Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected
Analysis 1.6
Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 6 Resolution of subperiosteal erosions.

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 6 Resolution of subperiosteal erosions.

6.1 Established vitamin D compounds

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6.2 Newer vitamin D compounds

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7 Development of vascular calcification Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only
Analysis 1.7
Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 7 Development of vascular calcification.

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 7 Development of vascular calcification.

7.1 Established vitamin D compounds

2

103

Risk Ratio (M‐H, Random, 95% CI)

1.09 [0.45, 2.67]

7.2 Newer vitamin D compounds

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8 Progression of vascular calcification Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected
Analysis 1.8
Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 8 Progression of vascular calcification.

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 8 Progression of vascular calcification.

8.1 Established vitamin D compounds

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.2 Newer vitamin D compounds

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9 Development of osteitis fibrosa Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected
Analysis 1.9
Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 9 Development of osteitis fibrosa.

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 9 Development of osteitis fibrosa.

9.1 Established vitamin D compounds

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

9.2 Newer vitamin D compounds

0

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

10 Development of osteomalacia Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected
Analysis 1.10
Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 10 Development of osteomalacia.

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 10 Development of osteomalacia.

10.1 Established vitamin D compounds

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

10.2 Newer vitamin D compounds

0

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

11 End of treatment parathyroid hormone (pg/mL) Show forest plot

6

212

Mean Difference (IV, Random, 95% CI)

‐196.05 [‐298.43, ‐93.66]
Analysis 1.11
Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 11 End of treatment parathyroid hormone (pg/mL).

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 11 End of treatment parathyroid hormone (pg/mL).

11.1 Established vitamin D compounds

4

104

Mean Difference (IV, Random, 95% CI)

‐220.54 [‐473.63, 32.55]

11.2 Newer vitamin D compounds

2

108

Mean Difference (IV, Random, 95% CI)

‐183.88 [‐217.88, ‐149.89]

12 Reduction in parathyroid hormone level by 30% Show forest plot

7

361

Risk Ratio (M‐H, Random, 95% CI)

5.90 [3.17, 10.96]
Analysis 1.12
Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 12 Reduction in parathyroid hormone level by 30%.

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 12 Reduction in parathyroid hormone level by 30%.

12.1 Established vitamin D compounds

1

47

Risk Ratio (M‐H, Random, 95% CI)

2.72 [1.12, 6.61]

12.2 Newer vitamin D compounds

6

314

Risk Ratio (M‐H, Random, 95% CI)

7.05 [3.82, 13.04]

13 End of treatment serum phosphorus (mg/dL) Show forest plot

2

105

Mean Difference (IV, Random, 95% CI)

0.70 [0.08, 1.33]
Analysis 1.13
Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 13 End of treatment serum phosphorus (mg/dL).

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 13 End of treatment serum phosphorus (mg/dL).

13.1 Established vitamin D compounds

1

27

Mean Difference (IV, Random, 95% CI)

0.60 [‐0.40, 1.60]

13.2 Newer vitamin D compounds

1

78

Mean Difference (IV, Random, 95% CI)

0.77 [‐0.04, 1.58]

14 One or more episodes of hyperphosphataemia Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only
Analysis 1.14
Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 14 One or more episodes of hyperphosphataemia.

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 14 One or more episodes of hyperphosphataemia.

14.1 Established vitamin D compound

2

59

Risk Ratio (M‐H, Random, 95% CI)

1.57 [0.97, 2.54]

14.2 Newer vitamin D compound

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

15 End of treatment serum calcium (mg/dL) Show forest plot

2

105

Mean Difference (IV, Random, 95% CI)

0.36 [‐0.26, 0.98]
Analysis 1.15
Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 15 End of treatment serum calcium (mg/dL).

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 15 End of treatment serum calcium (mg/dL).

15.1 Established vitamin D compounds

1

27

Mean Difference (IV, Random, 95% CI)

0.0 [‐0.61, 0.61]

15.2 Newer vitamin D compounds

1

78

Mean Difference (IV, Random, 95% CI)

0.64 [0.22, 1.06]

16 One or more episodes of hypercalcaemia Show forest plot

5

182

Risk Ratio (M‐H, Random, 95% CI)

3.80 [0.90, 16.12]
Analysis 1.16
Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 16 One or more episodes of hypercalcaemia.

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 16 One or more episodes of hypercalcaemia.

16.1 Established vitamin D compounds

3

74

Risk Ratio (M‐H, Random, 95% CI)

1.96 [0.62, 6.22]

16.2 Newer vitamin D compounds

2

108

Risk Ratio (M‐H, Random, 95% CI)

11.97 [1.48, 96.58]

17 Withdrawal of treatment due to hypercalcaemia Show forest plot

4

196

Risk Ratio (M‐H, Random, 95% CI)

4.17 [1.36, 12.77]
Analysis 1.17
Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 17 Withdrawal of treatment due to hypercalcaemia.

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 17 Withdrawal of treatment due to hypercalcaemia.

17.1 Established vitamin D compounds

2

88

Risk Ratio (M‐H, Random, 95% CI)

3.66 [0.96, 14.03]

17.2 Newer vitamin D compounds

2

108

Risk Ratio (M‐H, Random, 95% CI)

5.61 [0.74, 42.45]

18 One or more episodes of elevated calcium x phosphorus product Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected
Analysis 1.18
Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 18 One or more episodes of elevated calcium x phosphorus product.

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 18 One or more episodes of elevated calcium x phosphorus product.

18.1 Established vitamin D compounds

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

18.2 Newer vitamin D compounds

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

19 End of treatment alkaline phosphatase (U/L) Show forest plot

3

135

Mean Difference (IV, Random, 95% CI)

‐24.34 [‐44.34, ‐4.33]
Analysis 1.19
Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 19 End of treatment alkaline phosphatase (U/L).

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 19 End of treatment alkaline phosphatase (U/L).

19.1 Established vitamin D compounds

1

27

Mean Difference (IV, Random, 95% CI)

‐16.0 [‐54.83, 22.83]

19.2 Newer vitamin D compounds

2

108

Mean Difference (IV, Random, 95% CI)

‐27.35 [‐50.69, ‐4.01]
Open in table viewer
Comparison 2. Vitamin D compound versus vitamin D compound

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only
Analysis 2.1
Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 1 All‐cause mortality.

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 1 All‐cause mortality.

1.1 New versus established vitamin D compounds

2

103

Risk Ratio (M‐H, Random, 95% CI)

2.0 [0.19, 21.21]

2 Fracture Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only
Analysis 2.2
Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 2 Fracture.

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 2 Fracture.

2.1 New versus established vitamin D compounds

1

73

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3 Improvement in bone pain Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected
Analysis 2.3
Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 3 Improvement in bone pain.

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 3 Improvement in bone pain.

3.1 Active vitamin D compound versus vitamin D3

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4 Improvement in bone histomorphometry Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected
Analysis 2.4
Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 4 Improvement in bone histomorphometry.

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 4 Improvement in bone histomorphometry.

4.1 Active vitamin D compound versus vitamin D3

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5 End of treatment parathyroid hormone (pg/mL) Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Totals not selected
Analysis 2.5
Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 5 End of treatment parathyroid hormone (pg/mL).

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 5 End of treatment parathyroid hormone (pg/mL).

5.1 Active vitamin D compound versus vitamin D3

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

5.2 Calcitriol versus other established vitamin D compounds

1

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

5.3 New versus established vitamin D compounds

1

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

6 End of treatment serum phosphorus (mg/dL) Show forest plot

3

Mean Difference (IV, Random, 95% CI)

Subtotals only
Analysis 2.6
Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 6 End of treatment serum phosphorus (mg/dL).

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 6 End of treatment serum phosphorus (mg/dL).

6.1 Active vitamin D compound versus vitamin D3

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

6.2 Calcitriol versus another established vitamin D

2

91

Mean Difference (IV, Random, 95% CI)

0.52 [‐0.40, 1.44]

6.3 New versus established vitamin D compounds

1

73

Mean Difference (IV, Random, 95% CI)

‐0.31 [‐1.05, 0.43]

7 One or more episodes of hyperphosphataemia Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected
Analysis 2.7
Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 7 One or more episodes of hyperphosphataemia.

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 7 One or more episodes of hyperphosphataemia.

7.1 Active vitamin D compound versus vitamin D3

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.2 Calcitriol versus other established vitamin D compounds

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.3 New versus established vitamin D compounds

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8 End of treatment serum calcium (mg/dL) Show forest plot

4

Mean Difference (IV, Random, 95% CI)

Subtotals only
Analysis 2.8
Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 8 End of treatment serum calcium (mg/dL).

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 8 End of treatment serum calcium (mg/dL).

8.1 Active vitamin D compound versus vitamin D3

1

31

Mean Difference (IV, Random, 95% CI)

0.85 [0.35, 1.35]

8.2 Calcitriol versus other established vitamin D compounds

2

91

Mean Difference (IV, Random, 95% CI)

1.00 [‐0.56, 2.57]

8.3 New versus established vitamin D compounds

1

73

Mean Difference (IV, Random, 95% CI)

0.30 [‐0.11, 0.71]

9 End of treatment alkaline phosphatase (U/L)

0

Mean Difference (IV, Random, 95% CI)

Totals not selected

9.1 Active vitamin D versus vitamin D3

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

9.2 Calcitriol versus other established vitamin D compounds

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

9.3 New versus established vitamin D compounds

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

10 One or more episodes of hypercalcaemia Show forest plot

5

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only
Analysis 2.10
Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 10 One or more episodes of hypercalcaemia.

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 10 One or more episodes of hypercalcaemia.

10.1 Active vitamin D compound versus vitamin D3

2

53

Risk Ratio (M‐H, Random, 95% CI)

9.56 [1.32, 69.04]

10.2 Calcitriol versus other established vitamin D compounds

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.3 New versus established vitamin D compounds

3

125

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.26, 2.54]

11 Withdrawal of treatment due to hypercalcaemia Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only
Analysis 2.11
Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 11 Withdrawal of treatment due to hypercalcaemia.

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 11 Withdrawal of treatment due to hypercalcaemia.

11.1 Active vitamin D compound versus vitamin D3

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.2 Calcitriol versus other established vitamin D compounds

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.3 New versus established vitamin D compounds

2

52

Risk Ratio (M‐H, Random, 95% CI)

0.61 [0.17, 2.22]

12 Reduction in parathyroid hormone concentration by 50% Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected
Analysis 2.12
Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 12 Reduction in parathyroid hormone concentration by 50%.

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 12 Reduction in parathyroid hormone concentration by 50%.

12.1 New versus established vitamin D compounds

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Open in table viewer
Comparison 3. IV versus oral vitamin D compounds

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected
Analysis 3.1
Comparison 3 IV versus oral vitamin D compounds, Outcome 1 All‐cause mortality.

Comparison 3 IV versus oral vitamin D compounds, Outcome 1 All‐cause mortality.

2 Fracture Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected
Analysis 3.2
Comparison 3 IV versus oral vitamin D compounds, Outcome 2 Fracture.

Comparison 3 IV versus oral vitamin D compounds, Outcome 2 Fracture.

3 End of treatment absolute BMD femoral neck (g/cm²) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected
Analysis 3.3
Comparison 3 IV versus oral vitamin D compounds, Outcome 3 End of treatment absolute BMD femoral neck (g/cm²).

Comparison 3 IV versus oral vitamin D compounds, Outcome 3 End of treatment absolute BMD femoral neck (g/cm²).

4 End of treatment absolute BMD lumbar spine (g/cm²) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected
Analysis 3.4
Comparison 3 IV versus oral vitamin D compounds, Outcome 4 End of treatment absolute BMD lumbar spine (g/cm²).

Comparison 3 IV versus oral vitamin D compounds, Outcome 4 End of treatment absolute BMD lumbar spine (g/cm²).

5 End of treatment parathyroid hormone (pg/mL) Show forest plot

8

171

Mean Difference (IV, Random, 95% CI)

‐76.20 [‐150.92, ‐1.48]
Analysis 3.5
Comparison 3 IV versus oral vitamin D compounds, Outcome 5 End of treatment parathyroid hormone (pg/mL).

Comparison 3 IV versus oral vitamin D compounds, Outcome 5 End of treatment parathyroid hormone (pg/mL).

6 End of treatment serum phosphorus (mg/dL) Show forest plot

5

112

Mean Difference (IV, Random, 95% CI)

‐0.30 [‐0.58, ‐0.03]
Analysis 3.6
Comparison 3 IV versus oral vitamin D compounds, Outcome 6 End of treatment serum phosphorus (mg/dL).

Comparison 3 IV versus oral vitamin D compounds, Outcome 6 End of treatment serum phosphorus (mg/dL).

7 One or more episodes of hyperphosphataemia Show forest plot

5

102

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.65, 1.48]
Analysis 3.7
Comparison 3 IV versus oral vitamin D compounds, Outcome 7 One or more episodes of hyperphosphataemia.

Comparison 3 IV versus oral vitamin D compounds, Outcome 7 One or more episodes of hyperphosphataemia.

8 End of treatment serum calcium (mg/dL) Show forest plot

6

146

Mean Difference (IV, Random, 95% CI)

0.08 [‐0.35, 0.52]
Analysis 3.8
Comparison 3 IV versus oral vitamin D compounds, Outcome 8 End of treatment serum calcium (mg/dL).

Comparison 3 IV versus oral vitamin D compounds, Outcome 8 End of treatment serum calcium (mg/dL).

9 One of more episodes of hypercalcaemia Show forest plot

6

128

Risk Ratio (M‐H, Random, 95% CI)

1.11 [0.80, 1.52]
Analysis 3.9
Comparison 3 IV versus oral vitamin D compounds, Outcome 9 One of more episodes of hypercalcaemia.

Comparison 3 IV versus oral vitamin D compounds, Outcome 9 One of more episodes of hypercalcaemia.

10 End of treatment alkaline phosphatase (U/L) Show forest plot

4

116

Mean Difference (IV, Random, 95% CI)

3.61 [‐50.06, 57.28]
Analysis 3.10
Comparison 3 IV versus oral vitamin D compounds, Outcome 10 End of treatment alkaline phosphatase (U/L).

Comparison 3 IV versus oral vitamin D compounds, Outcome 10 End of treatment alkaline phosphatase (U/L).

Open in table viewer
Comparison 4. Intraperitoneal (IP) versus oral vitamin D compounds

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Improvement in bone histomorphometry Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected
Analysis 4.1
Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 1 Improvement in bone histomorphometry.

Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 1 Improvement in bone histomorphometry.

2 End of treatment parathyroid hormone (pg/mL) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected
Analysis 4.2
Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 2 End of treatment parathyroid hormone (pg/mL).

Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 2 End of treatment parathyroid hormone (pg/mL).

3 One or more episodes of hyperphosphataemia Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected
Analysis 4.3
Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 3 One or more episodes of hyperphosphataemia.

Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 3 One or more episodes of hyperphosphataemia.

4 One or more episodes of hypercalcaemia Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected
Analysis 4.4
Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 4 One or more episodes of hypercalcaemia.

Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 4 One or more episodes of hypercalcaemia.

Open in table viewer
Comparison 5. Intermittent versus daily vitamin D compounds

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Fracture Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected
Analysis 5.1
Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 1 Fracture.

Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 1 Fracture.

2 End of treatment parathyroid hormone (pg/mL) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected
Analysis 5.2
Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 2 End of treatment parathyroid hormone (pg/mL).

Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 2 End of treatment parathyroid hormone (pg/mL).

3 One or more episodes of hyperphosphataemia Show forest plot

3

97

Risk Ratio (M‐H, Random, 95% CI)

1.74 [0.44, 6.79]
Analysis 5.3
Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 3 One or more episodes of hyperphosphataemia.

Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 3 One or more episodes of hyperphosphataemia.

4 End of treatment serum phosphorus (mg/dL) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected
Analysis 5.4
Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 4 End of treatment serum phosphorus (mg/dL).

Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 4 End of treatment serum phosphorus (mg/dL).

5 One of more episodes of hypercalcaemia Show forest plot

4

118

Risk Ratio (M‐H, Random, 95% CI)

1.15 [0.36, 3.69]
Analysis 5.5
Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 5 One of more episodes of hypercalcaemia.

Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 5 One of more episodes of hypercalcaemia.

6 End of treatment serum calcium (mg/dL) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected
Analysis 5.6
Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 6 End of treatment serum calcium (mg/dL).

Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 6 End of treatment serum calcium (mg/dL).

7 End of treatment alkaline phosphatase (U/L)

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

Mechanisms for abnormal mineral metabolism in chronic kidney disease
Figuras y tablas -
Figure 1

Mechanisms for abnormal mineral metabolism in chronic kidney disease

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 1 All‐cause mortality.
Figuras y tablas -
Analysis 1.1

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 1 All‐cause mortality.

Ir a la figura de la revisiónAbrir en una pestaña nueva

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 2 Fracture.
Figuras y tablas -
Analysis 1.2

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 2 Fracture.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 3 Development of bone pain.
Figuras y tablas -
Analysis 1.3

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 3 Development of bone pain.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 4 Parathyroidectomy.
Figuras y tablas -
Analysis 1.4

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 4 Parathyroidectomy.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 5 Development of subperiosteal erosions.
Figuras y tablas -
Analysis 1.5

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 5 Development of subperiosteal erosions.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 6 Resolution of subperiosteal erosions.
Figuras y tablas -
Analysis 1.6

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 6 Resolution of subperiosteal erosions.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 7 Development of vascular calcification.
Figuras y tablas -
Analysis 1.7

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 7 Development of vascular calcification.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 8 Progression of vascular calcification.
Figuras y tablas -
Analysis 1.8

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 8 Progression of vascular calcification.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 9 Development of osteitis fibrosa.
Figuras y tablas -
Analysis 1.9

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 9 Development of osteitis fibrosa.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 10 Development of osteomalacia.
Figuras y tablas -
Analysis 1.10

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 10 Development of osteomalacia.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 11 End of treatment parathyroid hormone (pg/mL).
Figuras y tablas -
Analysis 1.11

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 11 End of treatment parathyroid hormone (pg/mL).

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 12 Reduction in parathyroid hormone level by 30%.
Figuras y tablas -
Analysis 1.12

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 12 Reduction in parathyroid hormone level by 30%.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 13 End of treatment serum phosphorus (mg/dL).
Figuras y tablas -
Analysis 1.13

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 13 End of treatment serum phosphorus (mg/dL).

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 14 One or more episodes of hyperphosphataemia.
Figuras y tablas -
Analysis 1.14

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 14 One or more episodes of hyperphosphataemia.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 15 End of treatment serum calcium (mg/dL).
Figuras y tablas -
Analysis 1.15

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 15 End of treatment serum calcium (mg/dL).

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 16 One or more episodes of hypercalcaemia.
Figuras y tablas -
Analysis 1.16

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 16 One or more episodes of hypercalcaemia.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 17 Withdrawal of treatment due to hypercalcaemia.
Figuras y tablas -
Analysis 1.17

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 17 Withdrawal of treatment due to hypercalcaemia.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 18 One or more episodes of elevated calcium x phosphorus product.
Figuras y tablas -
Analysis 1.18

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 18 One or more episodes of elevated calcium x phosphorus product.

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Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 19 End of treatment alkaline phosphatase (U/L).
Figuras y tablas -
Analysis 1.19

Comparison 1 Vitamin D compounds versus placebo/no treatment, Outcome 19 End of treatment alkaline phosphatase (U/L).

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 1 All‐cause mortality.
Figuras y tablas -
Analysis 2.1

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 1 All‐cause mortality.

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 2 Fracture.
Figuras y tablas -
Analysis 2.2

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 2 Fracture.

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 3 Improvement in bone pain.
Figuras y tablas -
Analysis 2.3

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 3 Improvement in bone pain.

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 4 Improvement in bone histomorphometry.
Figuras y tablas -
Analysis 2.4

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 4 Improvement in bone histomorphometry.

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 5 End of treatment parathyroid hormone (pg/mL).
Figuras y tablas -
Analysis 2.5

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 5 End of treatment parathyroid hormone (pg/mL).

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 6 End of treatment serum phosphorus (mg/dL).
Figuras y tablas -
Analysis 2.6

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 6 End of treatment serum phosphorus (mg/dL).

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 7 One or more episodes of hyperphosphataemia.
Figuras y tablas -
Analysis 2.7

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 7 One or more episodes of hyperphosphataemia.

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 8 End of treatment serum calcium (mg/dL).
Figuras y tablas -
Analysis 2.8

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 8 End of treatment serum calcium (mg/dL).

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 10 One or more episodes of hypercalcaemia.
Figuras y tablas -
Analysis 2.10

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 10 One or more episodes of hypercalcaemia.

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 11 Withdrawal of treatment due to hypercalcaemia.
Figuras y tablas -
Analysis 2.11

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 11 Withdrawal of treatment due to hypercalcaemia.

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Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 12 Reduction in parathyroid hormone concentration by 50%.
Figuras y tablas -
Analysis 2.12

Comparison 2 Vitamin D compound versus vitamin D compound, Outcome 12 Reduction in parathyroid hormone concentration by 50%.

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Comparison 3 IV versus oral vitamin D compounds, Outcome 1 All‐cause mortality.
Figuras y tablas -
Analysis 3.1

Comparison 3 IV versus oral vitamin D compounds, Outcome 1 All‐cause mortality.

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Comparison 3 IV versus oral vitamin D compounds, Outcome 2 Fracture.
Figuras y tablas -
Analysis 3.2

Comparison 3 IV versus oral vitamin D compounds, Outcome 2 Fracture.

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Comparison 3 IV versus oral vitamin D compounds, Outcome 3 End of treatment absolute BMD femoral neck (g/cm²).
Figuras y tablas -
Analysis 3.3

Comparison 3 IV versus oral vitamin D compounds, Outcome 3 End of treatment absolute BMD femoral neck (g/cm²).

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Comparison 3 IV versus oral vitamin D compounds, Outcome 4 End of treatment absolute BMD lumbar spine (g/cm²).
Figuras y tablas -
Analysis 3.4

Comparison 3 IV versus oral vitamin D compounds, Outcome 4 End of treatment absolute BMD lumbar spine (g/cm²).

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Comparison 3 IV versus oral vitamin D compounds, Outcome 5 End of treatment parathyroid hormone (pg/mL).
Figuras y tablas -
Analysis 3.5

Comparison 3 IV versus oral vitamin D compounds, Outcome 5 End of treatment parathyroid hormone (pg/mL).

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Comparison 3 IV versus oral vitamin D compounds, Outcome 6 End of treatment serum phosphorus (mg/dL).
Figuras y tablas -
Analysis 3.6

Comparison 3 IV versus oral vitamin D compounds, Outcome 6 End of treatment serum phosphorus (mg/dL).

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Comparison 3 IV versus oral vitamin D compounds, Outcome 7 One or more episodes of hyperphosphataemia.
Figuras y tablas -
Analysis 3.7

Comparison 3 IV versus oral vitamin D compounds, Outcome 7 One or more episodes of hyperphosphataemia.

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Comparison 3 IV versus oral vitamin D compounds, Outcome 8 End of treatment serum calcium (mg/dL).
Figuras y tablas -
Analysis 3.8

Comparison 3 IV versus oral vitamin D compounds, Outcome 8 End of treatment serum calcium (mg/dL).

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Comparison 3 IV versus oral vitamin D compounds, Outcome 9 One of more episodes of hypercalcaemia.
Figuras y tablas -
Analysis 3.9

Comparison 3 IV versus oral vitamin D compounds, Outcome 9 One of more episodes of hypercalcaemia.

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Comparison 3 IV versus oral vitamin D compounds, Outcome 10 End of treatment alkaline phosphatase (U/L).
Figuras y tablas -
Analysis 3.10

Comparison 3 IV versus oral vitamin D compounds, Outcome 10 End of treatment alkaline phosphatase (U/L).

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Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 1 Improvement in bone histomorphometry.
Figuras y tablas -
Analysis 4.1

Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 1 Improvement in bone histomorphometry.

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Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 2 End of treatment parathyroid hormone (pg/mL).
Figuras y tablas -
Analysis 4.2

Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 2 End of treatment parathyroid hormone (pg/mL).

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Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 3 One or more episodes of hyperphosphataemia.
Figuras y tablas -
Analysis 4.3

Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 3 One or more episodes of hyperphosphataemia.

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Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 4 One or more episodes of hypercalcaemia.
Figuras y tablas -
Analysis 4.4

Comparison 4 Intraperitoneal (IP) versus oral vitamin D compounds, Outcome 4 One or more episodes of hypercalcaemia.

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Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 1 Fracture.
Figuras y tablas -
Analysis 5.1

Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 1 Fracture.

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Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 2 End of treatment parathyroid hormone (pg/mL).
Figuras y tablas -
Analysis 5.2

Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 2 End of treatment parathyroid hormone (pg/mL).

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Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 3 One or more episodes of hyperphosphataemia.
Figuras y tablas -
Analysis 5.3

Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 3 One or more episodes of hyperphosphataemia.

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Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 4 End of treatment serum phosphorus (mg/dL).
Figuras y tablas -
Analysis 5.4

Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 4 End of treatment serum phosphorus (mg/dL).

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Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 5 One of more episodes of hypercalcaemia.
Figuras y tablas -
Analysis 5.5

Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 5 One of more episodes of hypercalcaemia.

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Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 6 End of treatment serum calcium (mg/dL).
Figuras y tablas -
Analysis 5.6

Comparison 5 Intermittent versus daily vitamin D compounds, Outcome 6 End of treatment serum calcium (mg/dL).

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Table 1. Stages of chronic kidney disease (KDOQI)

CKD stage

GFR range

1

≥ 90 mL/min/1.73 m² with kidney damage for ≥3 months as defined by structural or functional abnormalities of the kidney

2

60‐89 mL/min/1.73 m²

3

30‐59 mL/min

4

15‐29 mL/min

5

< 15 mL/min or dialysis
Figuras y tablas -
Table 1. Stages of chronic kidney disease (KDOQI)
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Table 2. Summary of extractable data for meta‐analysis

Comparison

(studies)

Studies

Patients

Studies with efficacy data extractable for meta‐analysis

Studies with adverse event data available

Studies/meta‐analysis (range)

Vitamin D versus placebo (18)

All studies combined

18

1297

14

8

1‐7

Established vitamin D

10

850

7

5

1‐4

Newer vitamin D

8

447

7

3

1‐6

Vitamin D versus vitamin D compound (13)

Active vitamin D versus vitamin D3

2

53

1

2

1‐2

Calcitriol versus another established vitamin D

3

101

1

2

1‐2

Established versus newer vitamin D

5

414

2

3

1‐2

Other comparisons

3

59

Meta‐analysis not possible

Vitamin D versus calcium (1)

All studies combined

1

47

Meta‐analysis not possible

IV versus oral vitamin D (12)

All studies combined

12

720

8

8

1‐6

Intraperitoneal versus oral vitamin D (3)

All studies combined

3

74

Meta‐analysis not possible

Subcutaneous versus oral vitamin D (1)

All studies combined

1

6

Meta‐analysis not possible

Intermittent versus daily vitamin D (5)

All studies combined

5

140

1

4

1‐4

Differing dosing schedules (7)

Differing frequency

3

57

Meta‐analysis not possible

Differing doses

3

195

Meta‐analysis not possible

Morning versus evening dosing

1

13

Meta‐analysis not possible
Figuras y tablas -
Table 2. Summary of extractable data for meta‐analysis
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Table 3. Current guidelines for the use of vitamin D compounds in chronic kidney disease

Guideline

Country

Year

Recommendation

Kidney Disease Outcomes Quality Initiative

USA

2003

Patients treated with HD or PD with serum levels of intact PTH levels > 300 pg/mL) (33.0 pmol/L) should receive an active vitamin D sterol (such as calcitriol, alfacalcidol, paricalcitol, or doxercalciferol) to reduce the serum levels of PTH to a target range of 150‐300 pg/mL (16.5‐33.0 pmol/L). (EVIDENCE)

The intermittent, IV administration of calcitriol is more effective than daily oral calcitriol in lowering serum PTH levels. (EVIDENCE)

In patients with corrected serum calcium and/or phosphorus levels above the target range, a study of alternative vitamin D analogs, such as paricalcitol or doxercalciferol may be warranted. (OPINION)

When either HD or PD patients are treated with active vitamin D sterols, management should integrate the changes in serum calcium, serum phosphorus, and plasma PTH.

Caring for Australasians with Renal Impairment

Australasia

2006

Oral calcitriol (intermittent or pulsed) is effective at lowering parathyroid hormone levels in patients on PD (Level II evidence).

Vitamin D and its analogs, either given orally daily, orally intermittently, or intravenously are effective at lowering PTH levels in patients on HD (Level I/II evidence).

Oral calcitriol is effective for the prevention or treatment of hyperparathyroidism in most patients on HD or PD. IV calcitriol may be more effective at lowering PTH levels and be less likely to cause hypercalcaemia but the lack of well‐designed studies of sufficient size prevents a more definitive statement.

Vitamin D analogs are effective at lowering PTH but clinical studies proving their effectiveness with fewer side‐effects prevents are either lacking or not definitive. On the basis of current evidence there is little reason to recommend their use over oral or IV calcitriol.

British Renal Society

UK

2007

The relative importance of hyperparathyroidism as a risk factor for premature vascular disease is difficult to determine from observational studies and no informative RCTs exist.

There is no doubt that a serum PTH concentration over 4 times the normal limit is associated with increased risk of significant bone disease and should therefore be avoided by medical (or if necessary surgical) management of hyperparathyroidism.

In the absence of firm evidence, individual clinicians should decide on the degree to which hyperparathyroidism should be corrects and how this should be achieved.

European Best Practice Guidelines (EBPG)

Europe

2002

No guideline

Europe ‐‐ expert panel (including members from Fresenius Medical Care) (not EBPG)

Europe

2001

PTH above 9‐18 pmol/L (78‐156 pg/mL) may well be treated with small daily doses of active vitamin D. IV pulse administration does not have any advantage over oral route. No evidence from direct comparative studies to show any superiority of maxacalcitol, doxercalciferol, or paricalcitol over calcitriol or alfacalcidol.

Canadian Society of Nephrology

Canada

2006

Avoid intact PTH (iPTH) levels < 100 pg/mL (10.6 pmol/L (Grade C); iPTH levels > 500 pg/mL (53 pmol/L) should be treated if accompanied by symptoms or clinical signs of hyperparathyroidism. Vitamin D analogs should be used in conjunction with a specialist.

There is insufficient evidence to recommend use of novel vitamin D analogs (grade D, opinion)

HD ‐ haemodialysis; PD ‐ peritoneal dialysis
Figuras y tablas -
Table 3. Current guidelines for the use of vitamin D compounds in chronic kidney disease
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Comparison 1. Vitamin D compounds versus placebo/no treatment

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

5

233

Risk Ratio (M‐H, Random, 95% CI)

1.34 [0.34, 5.24]

1.1 Established vitamin D compounds

3

168

Risk Ratio (M‐H, Random, 95% CI)

1.11 [0.24, 5.05]

1.2 Newer vitamin D compounds

2

65

Risk Ratio (M‐H, Random, 95% CI)

3.00 [0.13, 68.26]

2 Fracture Show forest plot

4

181

Risk Ratio (M‐H, Random, 95% CI)

1.0 [0.06, 15.41]

2.1 Established vitamin D compounds

3

103

Risk Ratio (M‐H, Random, 95% CI)

1.0 [0.06, 15.41]

2.2 Newer vitamin D compounds

1

78

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3 Development of bone pain Show forest plot

4

109

Risk Ratio (M‐H, Random, 95% CI)

0.29 [0.03, 2.63]

3.1 Established vitamin D compounds

3

74

Risk Ratio (M‐H, Random, 95% CI)

0.41 [0.02, 9.25]

3.2 Newer vitamin D compounds

1

35

Risk Ratio (M‐H, Random, 95% CI)

0.20 [0.01, 4.65]

4 Parathyroidectomy Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

4.1 Established vitamin D compounds

2

133

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.05, 12.47]

4.2 Newer vitamin D compounds

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5 Development of subperiosteal erosions Show forest plot

3

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

5.1 Established vitamin D compounds

3

120

Risk Ratio (M‐H, Random, 95% CI)

0.41 [0.07, 2.38]

5.2 Newer vitamin D compounds

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6 Resolution of subperiosteal erosions Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

6.1 Established vitamin D compounds

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

6.2 Newer vitamin D compounds

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7 Development of vascular calcification Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

7.1 Established vitamin D compounds

2

103

Risk Ratio (M‐H, Random, 95% CI)

1.09 [0.45, 2.67]

7.2 Newer vitamin D compounds

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8 Progression of vascular calcification Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

8.1 Established vitamin D compounds

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8.2 Newer vitamin D compounds

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

9 Development of osteitis fibrosa Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

9.1 Established vitamin D compounds

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

9.2 Newer vitamin D compounds

0

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

10 Development of osteomalacia Show forest plot

1

Odds Ratio (M‐H, Fixed, 95% CI)

Totals not selected

10.1 Established vitamin D compounds

1

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

10.2 Newer vitamin D compounds

0

Odds Ratio (M‐H, Fixed, 95% CI)

0.0 [0.0, 0.0]

11 End of treatment parathyroid hormone (pg/mL) Show forest plot

6

212

Mean Difference (IV, Random, 95% CI)

‐196.05 [‐298.43, ‐93.66]

11.1 Established vitamin D compounds

4

104

Mean Difference (IV, Random, 95% CI)

‐220.54 [‐473.63, 32.55]

11.2 Newer vitamin D compounds

2

108

Mean Difference (IV, Random, 95% CI)

‐183.88 [‐217.88, ‐149.89]

12 Reduction in parathyroid hormone level by 30% Show forest plot

7

361

Risk Ratio (M‐H, Random, 95% CI)

5.90 [3.17, 10.96]

12.1 Established vitamin D compounds

1

47

Risk Ratio (M‐H, Random, 95% CI)

2.72 [1.12, 6.61]

12.2 Newer vitamin D compounds

6

314

Risk Ratio (M‐H, Random, 95% CI)

7.05 [3.82, 13.04]

13 End of treatment serum phosphorus (mg/dL) Show forest plot

2

105

Mean Difference (IV, Random, 95% CI)

0.70 [0.08, 1.33]

13.1 Established vitamin D compounds

1

27

Mean Difference (IV, Random, 95% CI)

0.60 [‐0.40, 1.60]

13.2 Newer vitamin D compounds

1

78

Mean Difference (IV, Random, 95% CI)

0.77 [‐0.04, 1.58]

14 One or more episodes of hyperphosphataemia Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

14.1 Established vitamin D compound

2

59

Risk Ratio (M‐H, Random, 95% CI)

1.57 [0.97, 2.54]

14.2 Newer vitamin D compound

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

15 End of treatment serum calcium (mg/dL) Show forest plot

2

105

Mean Difference (IV, Random, 95% CI)

0.36 [‐0.26, 0.98]

15.1 Established vitamin D compounds

1

27

Mean Difference (IV, Random, 95% CI)

0.0 [‐0.61, 0.61]

15.2 Newer vitamin D compounds

1

78

Mean Difference (IV, Random, 95% CI)

0.64 [0.22, 1.06]

16 One or more episodes of hypercalcaemia Show forest plot

5

182

Risk Ratio (M‐H, Random, 95% CI)

3.80 [0.90, 16.12]

16.1 Established vitamin D compounds

3

74

Risk Ratio (M‐H, Random, 95% CI)

1.96 [0.62, 6.22]

16.2 Newer vitamin D compounds

2

108

Risk Ratio (M‐H, Random, 95% CI)

11.97 [1.48, 96.58]

17 Withdrawal of treatment due to hypercalcaemia Show forest plot

4

196

Risk Ratio (M‐H, Random, 95% CI)

4.17 [1.36, 12.77]

17.1 Established vitamin D compounds

2

88

Risk Ratio (M‐H, Random, 95% CI)

3.66 [0.96, 14.03]

17.2 Newer vitamin D compounds

2

108

Risk Ratio (M‐H, Random, 95% CI)

5.61 [0.74, 42.45]

18 One or more episodes of elevated calcium x phosphorus product Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

18.1 Established vitamin D compounds

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

18.2 Newer vitamin D compounds

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

19 End of treatment alkaline phosphatase (U/L) Show forest plot

3

135

Mean Difference (IV, Random, 95% CI)

‐24.34 [‐44.34, ‐4.33]

19.1 Established vitamin D compounds

1

27

Mean Difference (IV, Random, 95% CI)

‐16.0 [‐54.83, 22.83]

19.2 Newer vitamin D compounds

2

108

Mean Difference (IV, Random, 95% CI)

‐27.35 [‐50.69, ‐4.01]
Figuras y tablas -
Comparison 1. Vitamin D compounds versus placebo/no treatment
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Comparison 2. Vitamin D compound versus vitamin D compound

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 New versus established vitamin D compounds

2

103

Risk Ratio (M‐H, Random, 95% CI)

2.0 [0.19, 21.21]

2 Fracture Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

2.1 New versus established vitamin D compounds

1

73

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3 Improvement in bone pain Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

3.1 Active vitamin D compound versus vitamin D3

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

4 Improvement in bone histomorphometry Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

4.1 Active vitamin D compound versus vitamin D3

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

5 End of treatment parathyroid hormone (pg/mL) Show forest plot

2

Mean Difference (IV, Random, 95% CI)

Totals not selected

5.1 Active vitamin D compound versus vitamin D3

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

5.2 Calcitriol versus other established vitamin D compounds

1

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

5.3 New versus established vitamin D compounds

1

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

6 End of treatment serum phosphorus (mg/dL) Show forest plot

3

Mean Difference (IV, Random, 95% CI)

Subtotals only

6.1 Active vitamin D compound versus vitamin D3

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

6.2 Calcitriol versus another established vitamin D

2

91

Mean Difference (IV, Random, 95% CI)

0.52 [‐0.40, 1.44]

6.3 New versus established vitamin D compounds

1

73

Mean Difference (IV, Random, 95% CI)

‐0.31 [‐1.05, 0.43]

7 One or more episodes of hyperphosphataemia Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

7.1 Active vitamin D compound versus vitamin D3

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.2 Calcitriol versus other established vitamin D compounds

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

7.3 New versus established vitamin D compounds

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

8 End of treatment serum calcium (mg/dL) Show forest plot

4

Mean Difference (IV, Random, 95% CI)

Subtotals only

8.1 Active vitamin D compound versus vitamin D3

1

31

Mean Difference (IV, Random, 95% CI)

0.85 [0.35, 1.35]

8.2 Calcitriol versus other established vitamin D compounds

2

91

Mean Difference (IV, Random, 95% CI)

1.00 [‐0.56, 2.57]

8.3 New versus established vitamin D compounds

1

73

Mean Difference (IV, Random, 95% CI)

0.30 [‐0.11, 0.71]

9 End of treatment alkaline phosphatase (U/L)

0

Mean Difference (IV, Random, 95% CI)

Totals not selected

9.1 Active vitamin D versus vitamin D3

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

9.2 Calcitriol versus other established vitamin D compounds

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

9.3 New versus established vitamin D compounds

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]

10 One or more episodes of hypercalcaemia Show forest plot

5

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

10.1 Active vitamin D compound versus vitamin D3

2

53

Risk Ratio (M‐H, Random, 95% CI)

9.56 [1.32, 69.04]

10.2 Calcitriol versus other established vitamin D compounds

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

10.3 New versus established vitamin D compounds

3

125

Risk Ratio (M‐H, Random, 95% CI)

0.82 [0.26, 2.54]

11 Withdrawal of treatment due to hypercalcaemia Show forest plot

2

Risk Ratio (M‐H, Random, 95% CI)

Subtotals only

11.1 Active vitamin D compound versus vitamin D3

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.2 Calcitriol versus other established vitamin D compounds

0

0

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

11.3 New versus established vitamin D compounds

2

52

Risk Ratio (M‐H, Random, 95% CI)

0.61 [0.17, 2.22]

12 Reduction in parathyroid hormone concentration by 50% Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

12.1 New versus established vitamin D compounds

1

Risk Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]
Figuras y tablas -
Comparison 2. Vitamin D compound versus vitamin D compound
Ir a la tabla de la revisión
Comparison 3. IV versus oral vitamin D compounds

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 All‐cause mortality Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

2 Fracture Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

3 End of treatment absolute BMD femoral neck (g/cm²) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

4 End of treatment absolute BMD lumbar spine (g/cm²) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

5 End of treatment parathyroid hormone (pg/mL) Show forest plot

8

171

Mean Difference (IV, Random, 95% CI)

‐76.20 [‐150.92, ‐1.48]

6 End of treatment serum phosphorus (mg/dL) Show forest plot

5

112

Mean Difference (IV, Random, 95% CI)

‐0.30 [‐0.58, ‐0.03]

7 One or more episodes of hyperphosphataemia Show forest plot

5

102

Risk Ratio (M‐H, Random, 95% CI)

0.98 [0.65, 1.48]

8 End of treatment serum calcium (mg/dL) Show forest plot

6

146

Mean Difference (IV, Random, 95% CI)

0.08 [‐0.35, 0.52]

9 One of more episodes of hypercalcaemia Show forest plot

6

128

Risk Ratio (M‐H, Random, 95% CI)

1.11 [0.80, 1.52]

10 End of treatment alkaline phosphatase (U/L) Show forest plot

4

116

Mean Difference (IV, Random, 95% CI)

3.61 [‐50.06, 57.28]
Figuras y tablas -
Comparison 3. IV versus oral vitamin D compounds
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Comparison 4. Intraperitoneal (IP) versus oral vitamin D compounds

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Improvement in bone histomorphometry Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

2 End of treatment parathyroid hormone (pg/mL) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

3 One or more episodes of hyperphosphataemia Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

4 One or more episodes of hypercalcaemia Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected
Figuras y tablas -
Comparison 4. Intraperitoneal (IP) versus oral vitamin D compounds
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Comparison 5. Intermittent versus daily vitamin D compounds

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Fracture Show forest plot

1

Risk Ratio (M‐H, Random, 95% CI)

Totals not selected

2 End of treatment parathyroid hormone (pg/mL) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

3 One or more episodes of hyperphosphataemia Show forest plot

3

97

Risk Ratio (M‐H, Random, 95% CI)

1.74 [0.44, 6.79]

4 End of treatment serum phosphorus (mg/dL) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

5 One of more episodes of hypercalcaemia Show forest plot

4

118

Risk Ratio (M‐H, Random, 95% CI)

1.15 [0.36, 3.69]

6 End of treatment serum calcium (mg/dL) Show forest plot

1

Mean Difference (IV, Random, 95% CI)

Totals not selected

7 End of treatment alkaline phosphatase (U/L)

0

0

Mean Difference (IV, Random, 95% CI)

0.0 [0.0, 0.0]
Figuras y tablas -
Comparison 5. Intermittent versus daily vitamin D compounds
Ir a la tabla de la revisión