Scolaris Content Display Scolaris Content Display

Calcimiméticos para el hiperparatiroidismo secundario en pacientes con nefropatías crónicas

Collapse all Expand all

References

References to studies included in this review

ACHIEVE Study 2008 {published data only}

Charytan C, Corry D, Roppolo M, Ling X, Droge J, Fishbane S. Assessing the use of the calcimimetic cinacalcet with low dose vitamin D versus escalating doses of vitamin D alone in the treatment of secondary hyperparathyroidism (HPT) ‐ The ACHIEVE Study [abstract no: 39]. American Journal of Kidney Diseases 2007;49(4):A34. [CENTRAL: CN‐00615830]
Charytan C, Wetmore J, Moustafa M, Martinez C, Stewart T, Ling X, et al. Efficacy of treatments targeting the calcium‐sensing receptor (CaR) and vitamin D receptor (VDR) in controlling parathyroid hormone (PTH) in hemodialysis (HD) patients: cinacalcet HCI plus low‐dose vitamin D vs flexible vitamin D alone [abstract no: SU‐PO812]. Journal of the American Society of Nephrology 2007;18(Abstracts Issue):764A.
Fishbane S, Shapiro W, Corry D, Rappaport K, Vicks S, Ling X, et al. A comparison of cinacalcet HCI and low‐dose vitamin D vs escalating doses of vitamin D alone ‐ the ACHIEVE study [abstract no: PUB354]. Journal of the American Society of Nephrology 2006;17(Abstracts):891A. [CENTRAL: CN‐00615831]
Fishbane S, Shapiro WB, Corry DB, Vicks SL, Roppolo M, Rappaport K, et al. Cinacalcet HCl and concurrent low‐dose vitamin D improves treatment of secondary hyperparathyroidism in dialysis patients compared with vitamin D alone: the ACHIEVE study results. Clinical Journal of The American Society of Nephrology: CJASN 2008;3(6):1718‐25. [MEDLINE: 18945995]
Fishbane S, Vicks S, Ling X, Turner S, Charytan C. Cinacalcet with low dose vitamin D provides improved control of parathyroid hormone, calcium, and calcium‐phosphorus product in hemodialysis patients with secondary hyperparathyroidism compared with vitamin D alone [abstract no: SaP383]. Nephrology Dialysis Transplantation 2007;22(Suppl 6):vi363. [CENTRAL: CN‐00671779]
Fishbane S, Wetmore J, Moustafa M, Martinez C, Ling X, Turner S, et al. Treatment with cinacalcet HC1 and concurrent low‐dose vitamin D improved management of secondary hyperparathyroidism (SHPT) compared with vitamin D alone [abstract no: SU‐FC100]. Journal of the American Society of Nephrology 2007;18(Abstracts):89A.
Shireman TI, Almehmi A, Wetmore JB, Lu J, Pregenzer M, Quarles LD. Economic analysis of cinacalcet in combination with low‐dose vitamin D versus flexible‐dose vitamin D in treating secondary hyperparathyroidism in hemodialysis patients. American Journal of Kidney Diseases 2010;56(6):1108‐16. [MEDLINE: 20951487]
Wetmore JB, Liu S, Krebill R, Menard R, Quarles D. Treatment with cinacalcet plus vitamin D results in lower FGF23 levels than vitamin D alone [abstract no: SA‐PO2779]. Journal of the American Society of Nephrology 2008;19(Abstracts Issue):739A.
Wetmore JB, Liu S, Krebill R, Menard R, Quarles LD. Effects of cinacalcet and concurrent low‐dose vitamin D on FGF23 levels in ESRD. Clinical Journal of The American Society of Nephrology: CJASN 2010;5(1):110‐6. [MEDLINE: 19965548]

ADVANCE Study 2010 {published data only}

Floege J, Raggi P, Block GA, Torres PU, Csiky B, Naso A, et al. Study design and subject baseline characteristics in the ADVANCE Study: effects of cinacalcet on vascular calcification in haemodialysis patients. Nephrology Dialysis Transplantation 2010;25(6):1916‐23. [MEDLINE: 20110249]
Floege J, Sprague S, Droge J, Banos A, Chertow G. ADVANCE: the effect of cinacalcet + low‐dose vitamin D on vascular calcification in hemodialysis patients ‐ methods [abstract no: 60]. American Journal of Kidney Diseases 2007;49(4):A39.
Raggi P, Chertow GM, Torres PU, Csiky B, Naso A, Nossuli K, et al. The ADVANCE study: a randomized study to evaluate the effects of cinacalcet plus low‐dose vitamin D on vascular calcification in patients on hemodialysis. Nephrology Dialysis Transplantation 2011;26(4):1327‐39. [MEDLINE: 21148030]
Urena PA, Kopyt NP, Rodriguez M, Bridges IM, Dehmel B, Cooper K, et al. Efficacy of cinacalcet combined with low dose vitamin D in incident hemodialysis subjects with secondary hyperparathyroidism [abstract no: LB‐PO3145]. Journal of the American Society of Nephrology 2011;22(Abstracts):3B.

Akiba 2008 {published data only}

Akiba T, Akizawa T, Tsukamoto Y, Uchida E, Iwasaki M, Koshikawa S, et al. Dose determination of cinacalcet hydrochloride in Japanese hemodialysis patients with secondary hyperparathyroidism. Therapeutic Apheresis & Dialysis 2008;12(2):117‐25. [18387159]
Akiba T, Akizawa T, Uchida E, Tsukamoto Y, Koshikawa S, KRN1493 Study Group. Randomized, double blind, placebo‐controlled, dose‐finding parallel study for KRN1493 (cinacalcet HC1) in Japanese hemodialysis patients [abstract no: F‐PO764]. Journal of the American Society of Nephrology 2005;16:503A.
Akizawa T, Koshikawa S. Clinical study of cinacalcet in Japan. Therapeutic Apheresis & Dialysis 2008;12 Suppl 1:S13‐5. [MEDLINE: 19032520]

Block 2004a {published data only}

Block GA, Martin KJ, Turner SA, Avram MM, Hercz G, Abu‐Alfa AK, et al. Phase 3 study results demonstrate efficacy and safety of the calcimimetic cinacalcet HCI in hemodialysis patients with secondary hyperparathyroidism (HPT) [abstract no: SA‐PO743]. Journal of the American Society of Nephrology 2003;14(Nov):461A. [CENTRAL: CN‐00644280]
Block GA, Martin KJ, de Francisco AL, Turner SA, Avram MM, Suranyi MG, et al. Cinacalcet for secondary hyperparathyroidism in patients receiving hemodialysis. New England Journal of Medicine 2004;350(15):1516‐25. [MEDLINE: 15071126]
Coyne DW, Stegman MH, Azad H, Joy MS, Mischel SF, Pokroy N, et al. Cinacalcet HCI controls secondary hyperparathyroidism (HPT) regardless of gender, race, age, and geography in patients with chronic kidney disease (CKD) receiving dialysis. [abstract no: SA‐PO754]. Journal of the American Society of Nephrology 2003;14(Nov):464A.
Cunningham J, Chertow G, Goodman W, Danese M, Olson K, Klassen P, et al. The effect of cinacalcet HCl on parathyroidectomy, fracture, hospitalisation, and mortality in dialysis subjects with secondary hyperparathyroidism (HPT) [abstract]. 41st ERA‐EDTA Congress; 2004; May 15‐18; Lisbon (Portugal). 2004:219. [CN‐00509144]
Cunningham J, Danese M, Olson K, Klassen P, Chertow GM. Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health‐related quality of life in secondary hyperparathyroidism. Kidney international 2005;68(4):1793‐800. [MEDLINE: 16164656]
Frazao JM, Holzer H, Stummvoll HK, Bahner U, Wilkie M, Zani V, et al. Cinacalcet (Mimpara©/Sensipar©) maintains achievement of NKF‐K/DOQI treatment targets for secondary hyperparathyroidism (HPT) in patients on dialysis [abstract no: SP209]. Nephrology Dialysis Transplantation 2005;20(Suppl 5):v89.
Frazao JM, Messa P, Cunningham J, Evenepoel P, Shahapuni I, Urena P, et al. Early use of cinacalcet (Mimpara©/Sensipar©) in dialysis patients enables greatest achievement of NKF‐KDOQITM treatment targets for bone metabolism [abstract no: SO016]. Nephrology Dialysis Transplantation 2006;21(Suppl 4):iv8.
Frazao JM, Nicolini M, Torresgrossa JV, Kerr P, Jaeger PH, Sprague SM, et al. Cinacalcet HCl effectively reduces intact parathyroid hormone (iPTH) and Ca x P irrespective of the severity of secondary hyperparathyroidism (HPT) [abstract]. 41st ERA‐EDTA Congress; 2004; May 15‐18; Lisbon (Portugal). 2004:219.
Goodman WG, Fadda GZ, Finkelstein FO Mittman N, Lien YH, LeBlanc M, et al. Cinacalcet HCl is an effective primary therapy for the management of secondary hyperparathyroidism [abstract]. Journal of the American Society of Nephrology 2003;14(Program & Abstracts):460A.
Goodman WG, de Francisco AL, Mittman N, Messa P, Lien YH, Leblanc M, et al. Cinacalcet HCI (SensiparTM) effectively manages secondary hyperparathyroidism (HPT) in new to dialysis patients [abstract no: PUB477]. Journal of the American Society of Nephrology 2004;15(Oct):863A. [CENTRAL: CN‐00644149]
Goodman WG, de Francisco AL, Moe SM, Cunningham J, Martin KJ, McCary LC, et al. Cinacalcet HCI (SensiparTM) is an effective treatment for secondary hyperparathyroidism (HPT) in CKD patients on dialysis [abstract no: F‐PO984]. Journal of the American Society of Nephrology 2004;15(Oct):280A. [CENTRAL: CN‐00644151]
Lien YH, Silva AL, Whittman D. Effects of cinacalcet on bone mineral density in patients with secondary hyperparathyroidism. Nephrology Dialysis Transplantation 2005;20(6):1232‐7. [MEDLINE: 15840675]
Lien YH, Silva AL, Whittman D. Effects of cinacalcet on bone mineral density in patients with secondary hyperparathyroidism [abstract no: W‐PO40084]. Nephrology 2005;10(Suppl 1):A301.
Martin KJ, Sherrard DJ, Nassar G, Campbell P, Curzi M, McCary KJ, et al. Control of bio‐intact parathyroid hormone (PTH) levels with the calcimimetic Cinacalcet HCl in hemodialysis patients with secondary hyperparathyroidism (HPT) [abstract no: SA‐PO747]. Journal of the American Society of Nephrology 2003;14(Nov):462A. [CENTRAL: CN‐00583599]
Mittman N, de Francisco ALM, Drueke T, Fadda GZ, Arruda JA, Abu‐Alfa AK, et al. Phase 3 studies demonstrate effective control of PTH and Ca x P in patients treated with cinacalcet HCI [abstract no: 73]. American Journal of Kidney Diseases 2004;43(4):A33.
Moe SM, Chertow GM, Coburn JW, Quarles LD, Goodman WG, Block GA, et al. Achieving NKF‐K/DOQI bone metabolism and disease treatment goals with cinacalcet HCl. Kidney international 2005;67(2):760‐71. [CENTRAL: 15673327]
Sterrett JF, Strom J, Stummvoll HK, Bahner U, Disney A Soroka SD, et al. Long‐term treatment of secondary hyperparathyroidism (HPT) with cinacalcet (SensiparTM) in patients receiving dialysis [abstract]. Journal of the American Society of Nephrology 2004;15(Abstracts):275A. [CENTRAL: CN‐00583604]
Sterrett JR, Strom J, Stummvoll HK, Bahner U, Disney A, Soroka SD, et al. Cinacalcet HCI (Sensipar/Mimpara) is an effective chronic therapy for hemodialysis patients with secondary hyperparathyroidism. Clinical Nephrology 2007;68(1):10‐7. [MEDLINE: 17703830]
de Francisco A, Suranyi M, Cunningham J, Messa P, Locatelli F, Evenepoel P, et al. Greater achievement of NKF‐K/DOQI bone metabolism and disease targets with oral cinacalcet HCL in an EU/Australian phase 3 study in haemodialysis subjects [abstract]. 41st ERA‐EDTA Congress; 2004; May 15‐18; Lisbon (Portugal). 2004:319.
de Francisco AL, Suranyi M, Cunningham J, Messa P, Locatelli F, Evenepoel P, et al. Oral cinacalcet HCI (AMG 073) for the treatment of hemodialysis patients with secondary hyperparathyroidism (HPT): results of a European/Australian phase 3 study. [abstract no: SA‐PO742]. Journal of the American Society of Nephrology 2003;14(Nov):461A. [CENTRAL: CN‐00583675]

Charytan 2005 {published data only}

Charytan C, Coburn JW, Chonchol M, Herman J, Lien YH, Liu W, et al. Cinacalcet hydrochloride is an effective treatment for secondary hyperparathyroidism in patients with CKD not receiving dialysis. American Journal of Kidney Diseases 2005;46(1):58‐67. [MEDLINE: 15983958]
Coburn JW, Charytan C, Chonchol M, Herman J, Lien YH, Liu W, et al. Cinacalcet HCl is an effective treatment for secondary hyperparathyroidism (HPT) in patients with chronic kidney disease (CKD) not yet receiving dialysis [abstract]. Journal of the American Society of Nephrology 2003;14(Program & Abstracts):460A.

Chonchol 2009 {published data only}

Chonchol M, Kopyt N, Herman J, Charytan C, Pischette V, Olson KA, et al. Cinacalcet HCI reduces parathyroid hormone (PTH) in patients with stage 3 and 4 chronic kidney disease (CKD) [abstract no: 18]. American Journal of Kidney Diseases 2004;43(4):A19. [CENTRAL: CN‐00602122]
Chonchol M, Locatelli F, Abboud H, Charytan C, De Francisco A, Jolly S, et al. A randomized, double‐blind, placebo‐controlled study of cinacalcet in CKD not on dialysis [abstract no: SA‐PO867]. Journal of the American Society of Nephrology 2007;18(Abstracts):533A. [CENTRAL: CN‐00583853]
Chonchol M, Locatelli F, Abboud HE, Charytan C, de Francisco AL, Jolly S, et al. A randomized, double‐blind, placebo‐controlled study to assess the efficacy and safety of cinacalcet HCl in participants with CKD not receiving dialysis. American Journal of Kidney Diseases 2009;53(2):197‐207. [MEDLINE: 19110359]

El Shafey 2011 {published data only}

El‐Shafey EM, Alsahow AE, Alsaran K, Sabry AA, Atia M. Cinacalcet hydrochloride therapy for secondary hyperparathyroidism in hemodialysis patients. Therapeutic Apheresis & Dialysis 2011;15(6):547‐55. [MEDLINE: 22107691]

EVOLVE study 2007 {published data only}

Chertow G, Block G, Correa‐Rotter R, Drueke T, Floege J, Goodman W, et al. Evaluation of cinacalcet HCI therapy to lower cardiovascular events (EVOLVE) trial [abstract no: PUB359]. Journal of the American Society of Nephrology 2006;17(Abstracts):893A. [CENTRAL: CN‐00601998]
Chertow GM, Correa‐Rotter R, Block GA, Drueke TB, Floege J, Goodman WG, et al. Baseline characteristics of subjects enrolled in the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events (EVOLVE) trial. Nephrology Dialysis Transplantation 2012;27(7):2872‐9. [MEDLINE: 22529163]
Chertow GM, Pupim LB, Block GA, Correa‐Rotter R, Drueke TB, Floege J, et al. Evaluation of Cinacalcet Therapy to Lower Cardiovascular Events (EVOLVE): rationale and design overview. Clinical Journal of The American Society of Nephrology: CJASN 2007;2(5):898‐905. [MEDLINE: 17702710]
Evolve Trial Investigators, Chertow GM, Block GA, Correa‐Rotter R, Drueke TB, Floege J, et al. Effect of cinacalcet on cardiovascular disease in patients undergoing dialysis. New England Journal of Medicine 2012;367(26):2482‐94. [MEDLINE: 23121374]

Fukagawa 2008 {published data only}

Akizawa T, Koshikawa S. Clinical study of cinacalcet in Japan. Therapeutic Apheresis & Dialysis 2008;12 Suppl 1:S13‐5. [MEDLINE: 19032520]
Fukagawa M, Yumita S, Akizawa T, Tsukamoto Y, Uchida E, Iwasaki M, et al. Randomized, placebo‐controlled trial of cinacalcet (KRN1493) in Japanese dialysis patients with more severe hyperparathyroidism and longer dialysis vintage [abstract no: FP453]. Nephrology Dialysis Transplantation 2007;22(Suppl 6):vi171.
Fukagawa M, Yumita S, Akizawa T, Uchida E, Tsukamoto Y, Iwasaki M, et al. Cinacalcet (KRN1493) effectively decreases the serum intact PTH level with favorable control of the serum phosphorus and calcium levels in Japanese dialysis patients. Nephrology Dialysis Transplantation 2008;23(1):328‐35. [MEDLINE: 17717030]
Yumita S, Akizawa T, Uchida E, Tsukamoto Y, Koshikawa S, KRN1493 Study Group. A randomized, double blind, placebo‐controlled, 14 week study to assess the efficacy and safety of cinacalcet HCI in Japanese hemodialysis patients [abstract no: PUB348]. Journal of the American Society of Nephrology 2006;17(Abstracts):889A.

Goodman 2000 {published data only}

Goodman WG, Frazao JM, Goodkin DA, Turner S, Liu W, Coburn JW. The calcimimetic, R‐568, lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism [abstract]. Journal of the American Society of Nephrology 1999;10(Program & Abstracts):619A‐20A. [CENTRAL: CN‐00626084]
Goodman WG, Frazao JM, Goodkin DA, Turner SA, Liu W, Coburn JW. A calcimimetic agent lowers plasma parathyroid hormone levels in patients with secondary hyperparathyroidism. Kidney International 2000;58(1):436‐45. [MEDLINE: 10886592]

Goodman 2002 {published data only}

Goodman WG, Hladik GA, Turner SA, Blaisdell PW, Goodkin DA, Liu W, et al. Multiple doses of the calcimimetic AMG 073 reduce plasma parathyroid hormone in hemodialysis patients with secondary hyperparathyroidism (SHPT) [abstract]. Journal of the American Society of Nephrology 2000;11(Sept):576A.
Goodman WG, Hladik GA, Turner SA, Blaisdell PW, Goodkin DA, Liu W, et al. The calcimimetic agent AMG 073 lowers plasma parathyroid hormone levels in hemodialysis patients with secondary hyperparathyroidism. Journal of the American Society of Nephrology 2002;13(4):1017‐24. [MEDLINE: 11912261]

Harris 2004 {published data only}

Harris RZ, Padhi D, Marbury TC, Novelck RJ, Salfi M, Sullivan JT. Pharmacokinetics, pharmacodynamics and safety of cinacalcet hydrochloride in hemodialysis patients at doses up to 200 mg once daily. American Journal of Kidney Diseases 2004;44(6):1070‐6. [MEDLINE: 15558528]

IMPACT SHPT Study 2012 {published data only}

Ketteler M, Martin KJ, Cozzolino M, Goldsmith D, Sharma A, Khan S, et al. Paricalcitol versus cinacalcet plus low‐dose vitamin D for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis: study design and baseline characteristics of the IMPACT SHPT study. Nephrology Dialysis Transplantation 2012;27(5):1942‐9. [MEDLINE: 21931122]
Ketteler M, Martin KJ, Wolf M, Amdahl M, Cozzolino M, Goldsmith D, et al. Paricalcitol versus cinacalcet plus low‐dose vitamin D therapy for the treatment of secondary hyperparathyroidism in patients receiving haemodialysis: results of the IMPACT SHPT study. Nephrology Dialysis Transplantation 2012;27(8):3270‐8. [MEDLINE: 22387567]

Lindberg 2003 {published data only}

Lindberg JS, Moe SM, Goodman WG, Coburn JW, Sprague SM, Liu W, et al. The calcimimetic AMG 073 reduces parathyroid hormone and calcium x phosphorus in secondary hyperparathyroidism. Kidney International 2003;63(1):248‐54. [MEDLINE: 12472790]
Lindberg JS, Moe SM, Goodman WG, Coburn JW, Turner SA, Blaisdell PW, et al. The calcimimetic AMG073 reduces parathyroid hormone (PTH), phosphorus (P), and calcium x phosphorus product (Ca x P) in patients with ESRD and secondary hyperparathyroidism (SHPT) [abstract]. Journal of the American Society of Nephrology 2000;11(Sept):578A. [CENTRAL: CN‐00626121]

Lindberg 2005 {published data only}

Coyne DW, Stegman MH, Azad H, Joy MS, Mischel SF, Pokroy N, et al. Cinacalcet HCI controls secondary hyperparathyroidism (HPT) regardless of gender, race, age, and geography in patients with chronic kidney disease (CKD) receiving dialysis. [abstract no: SA‐PO754]. Journal of the American Society of Nephrology 2003;14(Nov):464A.
Cunningham J, Chertow G, Goodman W, Danese M, Olson K, Klassen P, et al. The effect of cinacalcet HCl on parathyroidectomy, fracture, hospitalisation, and mortality in dialysis subjects with secondary hyperparathyroidism (HPT) [abstract]. 41st ERA‐EDTA Congress; 2004; May 15‐18; Lisbon (Portugal). 2004:219. [CENTRAL: CN‐00509144]
Cunningham J, Danese M, Olson K, Klassen P, Chertow GM. Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health‐related quality of life in secondary hyperparathyroidism. Kidney international 2005;68(4):1793‐800. [MEDLINE: 16164656]
Frazao JM, Holzer H, Stummvoll HK, Bahner U, Wilkie M, Zani V, et al. Cinacalcet (Mimpara©/Sensipar©) maintains achievement of NKF‐K/DOQI treatment targets for secondary hyperparathyroidism (HPT) in patients on dialysis [abstract no: SP209]. Nephrology Dialysis Transplantation 2005;20(Suppl 5):v89.
Frazao JM, Messa P, Cunningham J, Evenepoel P, Shahapuni I, Urena P, et al. Early use of cinacalcet (Mimpara©/Sensipar©) in dialysis patients enables greatest achievement of NKF‐KDOQITM treatment targets for bone metabolism [abstract no: SO016]. Nephrology Dialysis Transplantation 2006;21(Suppl 4):iv8.
Frazao JM, Nicolini M, Torresgrossa JV, Kerr P, Jaeger PH, Sprague SM, et al. Cinacalcet HCl effectively reduces intact parathyroid hormone (iPTH) and Ca x P irrespective of the severity of secondary hyperparathyroidism (HPT). 41st ERA‐EDTA Congress; 2004; May 15‐18; Lisbon (Portugal). 2004:219.
Goodman WG, Fadda GZ, Finkelstein FO, Mittman N, Lien YH, LeBlanc M, et al. Cinacalcet HCl is an effective primary therapy for the management of secondary hyperparathyroidism [abstract]. Journal of the American Society of Nephrology 2003;14(Program & Abstracts):460A.
Goodman WG, de Francisco AL, Mittman N, Messa P, Lien YH, Leblanc M, et al. Cinacalcet HCI (SensiparTM) effectively manages secondary hyperparathyroidism (HPT) in new to dialysis patients [abstract no: PUB477]. Journal of the American Society of Nephrology 2004;15(Oct):863A. [CENTRAL: CN‐00644149]
Goodman WG, de Francisco AL, Moe SM, Cunningham J, Martin KJ, McCary LC, et al. Cinacalcet HCI (SensiparTM) is an effective treatment for secondary hyperparathyroidism (HPT) in CKD patients on dialysis [abstract no: F‐PO984]. Journal of the American Society of Nephrology 2004;15(Oct):280A. [CENTRAL: CN‐00644151]
Lindberg JS, Culleton B, Wong G, Borah MF, Clark RV, Shapiro WB, et al. Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: a randomized, double‐blind, multicenter study. Journal of the American Society of Nephrology 2005;16(3):800‐7. [MEDLINE: 15689407]
Lindberg JS, Culleton B, Wong G, Borah MF, Clark RV, Shapiro WB, et al. Phase 3 experience with cinacalcet HCI in hemodialysis (HD) and peritoneal dialysis (PD) patients with secondary HPT [abstract no: SA‐PO752]. Journal of the American Society of Nephrology 2003;14(Nov):463A. [CENTRAL: CN‐00626029]
Mittman N, Finkelstein F, Culleton B, Charytan C, Agarwal A, Albizem MA, et al. Cinacalcet HCI (SensiparTM) for the management of secondary hyperparathyroidism (HPT) in patients receiving peritoneal dialysis (PD) [abstract no: F‐PO985]. Journal of the American Society of Nephrology 2004;15(Oct):280A. [CENTRAL: CN‐00626108]
Mittman N, de Francisco AL, Drueke T, Fadda GZ, Arruda JA, Abu‐Alfa AK, et al. Phase 3 studies demonstrate effective control of PTH and Ca x P in patients treated with cinacalcet HCI [abstract no: 73]. American Journal of Kidney Diseases 2004;43(4):A33.
Moe SM, Chertow GM, Coburn JW, Quarles LD, Goodman WG, Block GA, et al. Achieving NKF‐K/DOQI bone metabolism and disease treatment goals with cinacalcet HCl. Kidney international 2005;67(2):760‐71. [MEDLINE: 15673327]

Malluche 2008 {published data only}

Cunningham J, Chertow G, Goodman W, Danese M, Olson K, Klassen P, et al. The effect of cinacalcet HCl on parathyroidectomy, fracture, hospitalisation, and mortality in dialysis subjects with secondary hyperparathyroidism (HPT) [abstract]. 41st ERA‐EDTA Congress; 2004; May 15‐18; Lisbon (Portugal). 2004:219. [CENTRAL: CN‐00509144]
Cunningham J, Danese M, Olson K, Klassen P, Chertow GM. Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health‐related quality of life in secondary hyperparathyroidism. Kidney international 2005;68(4):1793‐800. [MEDLINE: 16164656]
Goodman WG, de Francisco AL, Mittman N, Messa P, Lien YH, Leblanc M, et al. Cinacalcet HCI (SensiparTM) effectively manages secondary hyperparathyroidism (HPT) in new to dialysis patients [abstract no: PUB477]. Journal of the American Society of Nephrology 2004;15(Oct):863A. [CENTRAL: CN‐00644149]
Goodman WG, de Francisco AL, Moe SM, Cunningham J, Martin KJ, McCary LC, et al. Cinacalcet HCI (SensiparTM) is an effective treatment for secondary hyperparathyroidism (HPT) in CKD patients on dialysis [abstract no: F‐PO984]. Journal of the American Society of Nephrology 2004;15(Oct):280A. [CENTRAL: CN‐00644151]
Malluche HH, Monier‐Faugere MC, Wang G, Fraza OJ, Charytan C, Coburn JW, et al. An assessment of cinacalcet HCl effects on bone histology in dialysis patients with secondary hyperparathyroidism. Clinical Nephrology 2008;69(4):269‐78. [MEDLINE: 18397701]
Malluche HH, Monier‐Faugere MC, Wang G, Frazao JM, Charytan C, Coburn JW, et al. Cinacalcet HCl reduces bone turnover and bone marrow fibrosis in hemodialysis patients with secondary hyperparathyroidism (HPT) [abstract]. 41st ERA‐EDTA Congress; 2004; May 15‐18; Lisbon (Portugal). 2004:218‐9. [CENTRAL: CN‐00509338]

OPTIMA Study 2008 {published data only}

Frazao JM, Braun J, Messa P, Dehmel B, Mattin C, Wilkie M. Is serum phosphorus control related to parathyroid hormone control in dialysis patients with secondary hyperparathyroidism?. BMC Nephrology 2012;13:76. [MEDLINE: 22863242]
Frazao JM, Macario F, Yaqoob M, Bouman K, Braun J, von Albertini B, et al. The Optima Study: earlier intervention of cinacalcet HCL (Sensipar©/Mimpara©) enables greater achievement of KDOQIT secondary hyperparathyroidism (SHPT) targets in dialysis patients [abstract no: 45]. American Journal of Kidney Diseases 2006;47(4):A30. [CENTRAL: CN‐00644220]
Gonzalez MT, Hutchison AJ, Girndt M, Stahl‐Nilsson A, Zani V, Carter D, et al. Secondary hyperparathyroidism (HPT) in patients receiving peritoneal dialysis (PD) can be effectively managed with cinacalcet (Mimpara©/Sensipar©) [abstract no: SP359]. Nephrology Dialysis Transplantation 2006;21(Suppl 4):iv134.
Locatelli F, Macario F, Brink HS, Dhaene M, Pai P, Holzer H, et al. The OPTIMA study: efficacy of a cinacalcet (Mimpara©/Sensipar©) treatment algorithm to treat dialysis patients with elevated PTH and calcium‐phosphorus product (Ca x P) [abstract no: SP357]. Nephrology Dialysis Transplantation 2006;21(Suppl 4):iv133. [CENTRAL: CN‐00644212]
Messa P, Macario F, Yaqoob M, Bouman K, Braun J, von Albertini B, et al. The OPTIMA study: assessing a new cinacalcet (Sensipar/Mimpara) treatment algorithm for secondary hyperparathyroidism. Clinical Journal of The American Society of Nephrology: CJASN 2008;3(1):36‐45. [MEDLINE: 18178780]
Messa P, Motellon JL, OPTIMA Study Group. Optimizing the use of cinacalcet (Mimpara©/Sensipar©) and vitamin D: interim results from the OPTIMA study [abstract no: F‐PO758]. Journal of the American Society of Nephrology 2005;16:501A‐2A. [CENTRAL: CN‐00644221]
Messa P, Villa G, Braun J, Maduell F, Cruz J, Martin PY, et al. The OPTIMA study: lower doses of cinacalcet (Mimpara©/Sensipar©) are required to achieve KDOQITM secondary hyperparathyroidism (HPT) targets in dialysis patients with less severe disease [abstract no: MP324]. Nephrology Dialysis Transplantation 2006;21(Suppl 4):iv407. [CENTRAL: CN‐00583842]
Perrault L, Carter D, Molemans B, Maetzel A. Use of cinacalcet HCL (Mimpara©/Sensipar©) to control mineral metabolism in patients with end‐stage renal disease (ESRD) on dialysis complicated by secondary hyperparathyroidism (SHPT): a cost‐consequence analysis of cinacalcet HCL versus standard of care (SC) [abstract no: SP363]. Nephrology Dialysis Transplantation 2006;21(Suppl 4):iv136.
Wilkie M. A multi‐centre, randomised, open‐label study to compare the efficacy and safety of an oral calcimimetic agent (AMG 073) when two different vitamin D regimens are used in subjects with secondary hyperparathyroidism of end‐stage renal disease (ESRD). http://www.nihr.ac.uk/Profile/Pages/NRRResults.aspx?publication_id=N0059124801 (accessed 1 June 2014).
Wilkie M, Pontoriero G, Macario F, Yaqoob M, Bouman K, Braun J, et al. Impact of vitamin D dose on biochemical parameters in patients with secondary hyperparathyroidism receiving cinacalcet. Nephron 2009;112(1):c41‐50. [MEDLINE: 19365139]
Wilkie M, Salvadori M, De Meester J, Jofre R, Koopman MG, Leidig FM, et al. The OPTIMA study: optimising the dose of vitamin D (vit D) in the presence of cinacalcet (Mimpara©/Sensipar©) to obtain maximum clinical benefit [abstract no: SP358]. Nephrology Dialysis Transplantation 2006;21(Suppl 4):iv134. [CENTRAL: CN‐00583844]

Quarles 2003a {published data only}

Quarles LD, Sherrard DJ, Adler S, Rosansky SJ, McCary LC, Liu W, et al. The calcimimetic AMG 073 as a potential treatment for secondary hyperparathyroidism of end‐stage renal disease. Journal of the American Society of Nephrology 2003;14(3):575‐83. [MEDLINE: 12595492]

References to studies excluded from this review

Al‐Hilali 2011 {published data only}

Al‐Hilali N, Hussain N, Kawy YA, Al‐Azmi M. A novel dose regimen of cinacalcet in the treatment of severe hyperparathyroidism in hemodialysis patients. Saudi Journal of Kidney Diseases & Transplantation 2011;22(3):448‐55. [MEDLINE: 21566299]

Coburn 2000a {published data only}

Coburn JW, Barri YM, Turner SA, Blaisdell PW, Goodkin DA, Liu W, et al. Single doses of the calcimimetic AMG 073 reduce parathyroid hormone levels in a dose dependent manner in hemodialysis patients with secondary hyperparathyroidism [abstract]. Journal of the American Society of Nephrology 2000;11(Sept):573A‐4A. [CENTRAL: CN‐00550686]

CONTROL Study 2006 {published data only}

Chertow GM, Blumenthal S, Turner S, Roppolo M, Stern L, Chi EM, et al. Cinacalcet hydrochloride (Sensipar) in hemodialysis patients on active vitamin D derivatives with controlled PTH and elevated calcium x phosphate. Clinical Journal of The American Society of Nephrology: CJASN 2006;1(2):305‐12. [MEDLINE: 17699221]
Reed J, Keightley G, Blumenthal S, Bradley C, LaBrecque J, Turner S, et al. The CONTROL STUDY: enhanced achievement of NKF‐K/DOQI bone metabolism and disease targets using cinacalcet HCL (Sensipar) [abstract]. Journal of the American Society of Nephrology 2004;15(Abstracts):280A.

Cunningham 2003 {published data only}

Cunningham J, Holzer H, Reichel H, Braun J, Hawley C, Urena P, et al. Sustained, long‐term reductions in parathyroid hormone (iPTH) after 3 years of treatment with calcimimetic cinacalcet HCl in patients with secondary hyperparathyroidism (SPTH) [abstract no: M479]. Nephrology Dialysis Transplantation 2003;18(Suppl 4):150‐1. [CENTRAL: CN‐00583594]

Cunningham 2005 {published data only}

Cunningham J, Urena P, Reichel H, Holzer H, Drueke T, Zani V, et al. Long term efficacy of cinacalcet in secondary hyperparathyroidism (HPT) of end stage renal disease (ESRD) [abstract no: SP210]. Nephrology Dialysis Transplantation 2005;20(Suppl 5):v89.

de Francisco 2005 {published data only}

De Francisco A, Evenepoel P, Brink HS, Mellotte G, Barata JD, Zani V, et al. Cinacalcet (Mimpara©/Sensipar©) effectively reduces intact parathyroid hormone (iPTH) and serum calcium (CA) regardless of serum calcium level in patients with secondary hyperparathyroidism (HPT) [abstract no: MO30]. Nephrology Dialysis Transplantation 2005;20(Suppl 5):v197.

Harris 2003 {published data only}

Harris R, Padhi D, Salfi M, Yates W, Simiens MA, Sulivan JT. Pharmacokinetics (PK), pharmacodynamics (PD), and safety of daily administration of cinacalcet HCI up to 300 mg in chronic kidney disease (CKD) patients on hemodialysis (HD) [abstract no: SA‐PO746]. Journal of the American Society of Nephrology 2003;14(Nov):462A. [CENTRAL: CN‐00583298]

Kaperonis 2012 {published data only}

Kaperonis N, Kourvelou C, Sgantzos A, Nastou D, Ntatsis G, Ziakka S, et al. Cinacalcet vs. paricalcitol in hemodialysis patients [abstract]. Nephrology Dialysis Transplantation 2012;27(Suppl 2):ii497‐8.

Moe 2003a {published data only}

Moe SM, Sprague SM, Cunningham J, Drueke T, Adler S, Rosansky SJ, et al. Long‐term treatment of secondary hyperparathyroidism (HPT) with the calcimimetic cinacalcet HCI [abstract no: SA‐PO753]. Journal of the American Society of Nephrology 2003;14:463A‐4A.

Moe 2005 {published data only}

Belozeroff V, Goodman W, Ren L, Kalantar‐Zadeh K. Cinacalcet lowers serum alkaline phosphatase (alkPhos) in maintenance hemodialysis (MHD) patients [abstract no: SA‐PO698]. Journal of the American Society of Nephrology 2007;18(Abstracts Issue):495A‐6A.
Bushinsky DA, Avram MM, Abu‐Alfa AK, Borah MF, Shapiro WB, Olson KA, et al. Characterization of the effects of cinacalcet HC1 (Sensipar©/Mimpara©) on serum calcium in dialysis patients with secondary hyperparathyroidism (HPT) [abstract no: F‐PO756]. Journal of the American Society of Nephrology 2005;16:501A. [CENTRAL: CN‐00583862]
Moe SM, Coburn JW, Quarles LD, Goodman WG, Chertow GM, Block GA, et al. Achievement of proposed NKF‐K/DOQI bone metabolism and disease targets: treatment with cinacalcet HCl in dialysis patients with uncontrolled secondary hyperparathyroidism (HPT) [abstract no: SU‐FC217]. Journal of the American Society of Nephrology 2003;14(Nov):48A.
Moe SM, Goodman WG, Cunningham J, Drueke T, Adler S, Rosansky SJ, et al. Cinacalcet HC1 sustains long‐term control of secondary hyperparathyroidism (HPT) [abstract no: F‐PO755]. Journal of the American Society of Nephrology 2005;16:501A.

Moe 2005b {published data only}

Moe SM, Cunningham J, Bommer J, Adler S, Rosansky SJ, Urena‐Torres P, et al. Long‐term treatment of secondary hyperparathyroidism with the calcimimetic cinacalcet HCl. Nephrology Dialysis Transplantation 2005;20(10):2186‐93. [MEDLINE: 16030053]

Padhi 2003 {published data only}

Padhi D, Harris R, Salfi M, Yates W, Hansen J, Flynn J, et al. Cinacalcet HCI absorption in study subjects is not affected by coadministration of medications commonly prescribed to chronic kidney disease (CKD) patients (pantoprazole, sevelamer HCI, and calcium carbonate). [abstract no: SA‐PO744]. Journal of the American Society of Nephrology 2003;14:461A.

Pahl 1996 {published data only}

Pahl M, Jara A, Bover J, Rodriguez M, Felsenfeld AJ. The set point of calcium and the reduction of parathyroid hormone in hemodialysis patients. Kidney international 1996;49(1):226‐31. [MEDLINE: 8770972]

Quarles 2003 {published data only}

Quarles LD, Zeig S, Spiegel DM, Silver MR, Vokes TJ, Torregrosa JV, et al. Cinacalcet HCl controls secondary hyperparathyroidism (HPT) in dialysis patients regardless of disease severity [abstract]. Journal of the American Society of Nephrology 2003;14(Program & Abstracts):463A.

Schaefer 2008 {published data only}

Schaefer RM, Bover J, Dellanna F, Sanz D, Asensio C, Sanchez GM, et al. Efficacy of cinacalcet administered with the first meal after dialysis: the SENSOR Study. Clinical Nephrology 2008;70(2):126‐34. [MEDLINE: 18793528]
Schaefer RM, Bover J, Kleophas W, Sanz D, Asensio C, Alonso JL, et al. The SENSOR study: a study to evaluate the efficacy of administering cinacalcet (Mimpara©/Sensipar©) with the first meal after dialysis [abstract no: MO003]. Nephrology Dialysis Transplantation 2006;21(Suppl 4):iv288. [CENTRAL: CN‐00671819]

Sezer 2012 {published data only}

Sezer S, Tutal E, Bal Z, Ozelsancak R, Demirci BG, Torun D, et al. Treatment of secondary hyperparathyroidism in maintenance hemodialysis patients: a randomised clinical trial comparing paricalcitol, calcitriol and cinacalcet [abstract]. Nephrology Dialysis Transplantation 2012;27(Suppl 2):ii509‐10.

TARGET Study 2008 {published data only}

Block GA, Zeig S, Sugihara J, Chertow GM, Chi EM, Turner SA, et al. Combined therapy with cinacalcet and low doses of vitamin D sterols in patients with moderate to severe secondary hyperparathyroidism. Nephrology Dialysis Transplantation 2008;23(7):2311‐8. [MEDLINE: 18310602]
Chertow GM, Corpier C, Zieg S, Stegman M, Lynn R, Abu‐Alfa AK, et al. Preliminary results from TARGET: treatment strategies to achieve recommended K/DOQI goals in ESRD patients on Cinacalcet [abstract]. Journal of the American Society of Nephrology 2004;15(Abstracts):863A.
Chertow GM, Lu ZJ, Xu X, Knight TG, Goodman WG, Bushinsky DA, et al. Self‐reported symptoms in patients on hemodialysis with moderate to severe secondary hyperparathyroidism receiving combined therapy with cinacalcet and low‐dose vitamin D sterols. Hemodialysis International 2012;16(2):188‐97. [MEDLINE: 22118402]

References to studies awaiting assessment

Coburn 2003 {published data only}

Coburn JW, Charytan C, Chonchol M, Herman J, Lien YH, Liu W, et al. Cinacalcet HCl is an effective treatment for secondary hyperparathyroidism (HPT) in patients with chronic kidney diseases (CKD) not receiving dialysis [abstract]. Journal of the American Society of Nephrology 2003;14(Program & Abstracts):460A.

Drueke 2001a {published data only}

Drueke T, Cunningham J, Goodman WG, Horl WH, Braun J, Chen MG, et al. Short‐term treatment of secondary hyperparathyroidism (SHPT) with the calcimimetic agent AMG 073 [abstract]. Journal of the American Society of Nephrology 2001;12(Program & Abstracts):764A. [CENTRAL: CN‐00550690]

Fournier 2004a {published data only}

Fournier A, Pontoiero G, Walker R, Martin‐Malo A, Wilkie M, Coyne DW, et al. Cinacalcet HCL reduces parathyroid hormone (PTH) and calcium‐phosphate product (Ca x P) regardless of concurrent changes in vitamin D administration [abstract]. 41st ERA‐EDTA Congress; 2004; May 15‐18; Lisbon (Portugal). 2004:319. [CENTRAL: CN‐00509198]

UPen 2004a {published data only}

University of Pennsylvania, Renal Electrolyte, Hypertension Division. 2004. A randomized, double‐blind, placebo‐controlled study to assess the safety and efficacy of a calcimimetic agent (AMG 073) in subjects with secondary hyperparathyroidism of chronic renal insufficiency. http://www.uphs.upenn.edu/renal/research/clinical_research_chronic_kidney.html (accessed 2 June 2014).

Albaaj 2003

Albaaj F, Hutchison A. Hyperphosphataemia in renal failure: causes, consequences and current management. Drugs 2003;63(6):577‐96. [MEDLINE: 12656655]

Avram 1996

Avram MM, Sreedhara R, Avram DK, Muchnick RA, Fein P. Enrollment parathyroid hormone level is a new marker of survival in hemodialysis and peritoneal dialysis therapy for uremia. American Journal of Kidney Diseases 1996;28(6):924‐30. [MEDLINE: 8957048]

Besarab 1998

Besarab A, Bolton WK, Browne JK, Egrie JC, Nissenson AR, Okamoto DM, et al. The effects of normal, as compared with low, hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. New England Journal of Medicine 1998;339(9):584‐90. [MEDLINE: 9718377]

Block 2004b

Block GA, Klassen PS, Lazarus LM, Ofsthun N, Lowrie EG, Chertow GM. Mineral metabolism, mortality and morbidity in maintenance hemodialysis. Journal of the American Society of Nephrology 2004;15(8):2208‐10. [MEDLINE: 15284307]

Borrows 2004

Borrows R, Loucaidou M, Van Tromp J, Cairns T, Griffith M, Hakim N, et al. Steroid sparing with tacrolimus and mycophenolate mofetil in renal transplantation. American Journal of Transplantation 2004;4(11):1845‐51. [MEDLINE: 15476485]

Bucher 1999

Bucher HC, Guyatt GH, Cook DJ, Holbrook A, McAlister FA. Users' guides to the medical literature: XIX. Applying clinical trial results. A. How to use an article measuring the effect of an intervention on surrogate end points. Evidence‐Based Medicine Working Group. JAMA 1999;282(8):771‐8. [MEDLINE: 10463714]

Churchill 1997

Churchill DN, Thorpe KE, Vonesh EF, Keshaviah PR. Lower probability of patient survival with continuous peritoneal dialysis in the united states compared with Canada. Canada‐USA (CANUSA) Peritoneal Dialysis Study Group. Journal of the American Society of Nephrology 1997;8(6):965‐71. [MEDLINE: 9189865]

Courant 1993

Courant O, Letessier E, Moutel MG, Hamy A, Paineau J, Visset J. Surgical treatment of secondary hyperparathyroidism in chronic kidney failure. Results of total parathyroidectomy with parathyroid autotransplantation. Journal de Chirurgie 1993;130(8‐9):327‐34. [MEDLINE: 8253879]

Cunningham 2005a

Cunningham J, Danese M, Olson K, Klassen P, Chertow GM. Effects of the calcimimetic cinacalcet HCl on cardiovascular disease, fracture, and health‐related quality of life in secondary hyperparathyroidism. Kidney international 2005;68(4):1793‐800. [MEDLINE: 16164656]

Egger 1998

Egger M, Smith GD. Bias in location and selection of studies. BMJ 1998;316(7124):61‐6. [MEDLINE: 9451274]

FDA 2004

US Food, Drug Administration. Sensipar (cinacalcet HCl) tablets. http://www.fda.gov/safety/medwatch/safetyinformation/ucm194427.htm (accessed 2 June 2014).

Ganesh 2001

Ganesh SK, Stack AG, Levin NW, Hulbert‐Shearon T, Port FK. Association of elevated serum PO(4), Ca x PO(4) product, and parathyroid hormone with cardiac mortality risk in chronic hemodialysis patient. Journal of the American Society of Nephrology 2001;12(10):2131‐8. [MEDLINE: 11562412]

Guyatt 2008

Guyatt GH, Oxman A D, Vist GE, Kunz R, Falck‐Ytter Y, Alonso‐Coello P, et al. GRADE: an emerging consensus on rating quality of evidence and strength of recommendations. BMJ 2008;336(7650):924‐6. [MEDLINE: 18436948]

Higgins 2003

Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta‐analyses. BMJ 2003;327(7414):557‐60. [MEDLINE: 12958120]

Higgins 2011

Higgins JP, Green S (editors). Cochrane Handbook for Systematic Reviews of Interventions Version 5.1.0 [updated March 2011]. The Cochrane Collaboration, 2011. Available from www.cochrane‐handbook.org.

Hutchison 1993

Hutchison AJ, Whitehouse RW, Boulton HF, Adams JE, Mawer EB, Freemont TJ, et al. Correlation of bone histology with parathyroid hormone, vitamin D3, and radiology in end‐stage renal disease. Kidney international 1995;26(5):622‐31. [MEDLINE: 8264137]

Juni 2003

Juni P, Sterchi R, Dieppe P. Systematic review of celecoxib for osteoarthritis and rheumatoid arthritis. Problems compromise review's validity. BMJ 2003;326(7384):334. [MEDLINE: 12574052]

KDIGO CKD 2013

Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney International ‐ Supplement 2013;3:1‐150.

Kestenbaum 2004

Kestenbaum B, Seliger SL, Gillen DL, Wasse H, Young B, Sherrard DJ, et al. Parathyroidectomy rates among United States dialysis patients: 1990‐1999. Kidney International 2004;65(1):282‐8. [MEDLINE: 14675061]

Kestenbaum 2005

Kestenbaum B, Sampson JN, Rudser KD, Patterson DJ, Seliger SL, Young B, et al. Serum phosphate levels and mortality risk among people with chronic kidney disease. Journal of the American Society of Nephrology 2005;16(2):520‐8. [MEDLINE: 15615819]

KHA‐CARI 2014

KHA‐CARI guidelines. http://www.cari.org.au/ (accessed 2 June 2014).

Lexchin 2003

Lexchin J, Bero LA, Djulbegovic B, Clark O. Pharmaceutical industry sponsorship and research outcome and quality: systematic review. BMJ 2003;326(7400):1167‐70. [MEDLINE: 12775614]

Malluche 2004b

Malluche HH, Mawad H, Monier‐Faugere MC. The importance of bone health in end‐stage renal disease: out of the frying pan, into the fire?. Nephrology Dialysis Transplantation 2004;19 Suppl 1:i9‐13. [MEDLINE: 15126648]

Marco 2003

Marco MP, Craver L, Betriu A, Belart M, Fibla J, Fernandez E. Higher impact of mineral metabolism on cardiovascular mortality in a European hemodialysis population. Kidney International ‐ Supplement 2003;85:S111‐4. [MEDLINE: 12753279]

Martin 2004

Martin KJ, Olgaard K, Coburn JW, Coen GM, Fukagawa M, Langman C, et al. Diagnosis, assessment and treatment of bone turnover abnormalities in renal osteodystrophy. American Journal of Kidney Diseases 2004;43(3):558‐65. [MEDLINE: 14981615]

McMahon 2004

McMahon LP, Roger SD, Levin A, SLIMHEART Investigators Group. Development, prevention and potential reversal of left ventricular hypertrophy in chronic kidney disease. Journal of the American Society of Nephrology 2004;15(6):1640‐7. [MEDLINE: 15153576]

Mentaverri 2006

Mentaverri R, Yano S, Chattopadhyay N, Petit L, Kifor O, Kamel S, et al. The calcium sensing receptor is directly involved in both osteoclast differentiation and apoptosis. FASEB Journal 2006;20(14):2562‐4. [MEDLINE: 17077282]

Mizobuchi 2007

Mizobuchi M, Ogata H, Hatamura I, Saji F, Koiwa F, Kinugasa E, et al. Activation of calcium‐sensing receptor accelerates apoptosis in hyperplastic parathyroid cells. Biochemical & Biophysical Research Communications 2007;362(1):11‐6. [MEDLINE: 17706605]

NICE 2007

NICE: National Institute for Health and Care Excellence. TA117 Hyperparathyroidism ‐ cinacalcet guidance (24 January 2007). http://guidance.nice.org.uk/TA117/Guidance/ (accessed 2 June 2014).

NKF 2003

National Kidney Foundation. K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease. American Journal of Kidney Diseases 2003;42(4 Suppl 3):S1‐210. [MEDLINE: 14520607]

Psaty 1999

Psaty BM, Weiss NS, Furberg CD, Koepsell TD, Siscovick DS, Rosendaal FR, et al. Surrogate end points, health outcomes, and the drug‐approval process for the treatment of risk factors for cardiovascular disease. JAMA 1999;282(8):786‐90. [MEDLINE: 10463718]

Qi 1995

Qi Q, Monier‐Faugere MC, Geng Z, Malluche HH. Predictive value of serum parathyroid hormone levels for bone turnover in patients on chronic maintenance dialysis. American Journal of Kidney Diseases 1995;26(4):622‐31. [MEDLINE: 7573017]

Simes 1986

Simes RJ. Publication bias: the case for an international registry of clinical trials. Journal of Clinical Oncology 1986;4(10):1529‐41. [MEDLINE: 3760920]

Stehman‐Breen 2004

Stehman‐Breen C. Osteoporosis and chronic kidney disease. Seminars in Nephrology 2004;24(1):78‐81. [MEDLINE: 14730513]

Stevens 2004

Stevens LA, Djurdjev O, Cardew S, Cameron EC, Levin A. Calcium, phosphate, and parathyroid hormone levels in combination and as a function of dialysis duration predict mortality: evidence for the complexity of the association between mineral metabolism and outcomes. Journal of the American Society of Nephrology 2004;15(3):770‐9. [MEDLINE: 14978180]

Temple 1999

Temple R. Are surrogate markers adequate to assess cardiovascular disease drugs?. JAMA 1999;282(8):790‐5. [MEDLINE: 10463719]

Urena 2003

Urena P, Frazao JM. Calcimimetic agents: review and perspectives. Kidney International ‐ Supplement 2003;85:S91‐6. [MEDLINE: 12753275]

USRDS 2012

Collins AJ, Foley RN, Herzog C, Chavers B, Gilbertson D, Herzog C, et al. United States Renal Data System 2012 annual data report: atlas of chronic kidney disease and end‐stage renal disease in the United States. American Journal of Kidney Diseases 2013;61(1 Suppl 1):e1‐e480.

Wang 1995

Wang M, Hercz G, Sherrard DJ, Maloney NA, Segre GV, Pei Y. Relationship between intact 1‐84 parathyroid hormone and bone histomorphometric parameters in dialysis patients without aluminum toxicity. American Journal of Kidney Diseases 1995;26(5):836‐44. [MEDLINE: 7485142]

Weiner 2006

Weiner DE, Tabatabai S, Tighiouart H, Elsayed E, Bansal N, Griffith J, et al. Cardiovascular outcomes and all‐cause mortality: exploring the interaction between CKD and cardiovascular disease. American Journal of Kidney Diseases 2006;48(3):392‐401. [MEDLINE: 16931212]

Ziolkowska 2000

Ziolkowska H, Paniczyk‐Tomaszewska M, Debinski A, Polowiec Z, Sawicki A, Sieniawska M. Bone biopsy results and serum bone turnover parameters in uremic children. Acta Paediatrica 2000;89(6):666‐71. [MEDLINE: 10914959]

References to other published versions of this review

Palmer 2013

Palmer SC, Nistor I, Craig JC, Pellegrini F, Messa P, Tonelli M, et al. Cinacalcet in patients with chronic kidney disease: a cumulative meta‐analysis of randomized controlled trials. PLoS Medicine 2013;10(4):e1001436. [MEDLINE: 23637579]

Strippoli 2006a

Strippoli GF, Tong A, Palmer SC, Elder G, Craig JC. Calcimimetics for secondary hyperparathyroidism in chronic kidney disease patients. Cochrane Database of Systematic Reviews 2006, Issue 4. [DOI: 10.1002/14651858.CD006254]

Strippoli 2006b

Strippoli GF, Palmer S, Tong A, Elder G, Messa P, Craig JC. Meta‐analysis of biochemical and patient‐level effects of calcimimetic therapy. American Journal of Kidney Diseases 2006;47(5):715‐26. [MEDLINE: 16632010]

Characteristics of studies

Characteristics of included studies [ordered by study ID]

ACHIEVE Study 2008

Methods

  • Study design: parallel, open‐label RCT

  • Study duration: NS

  • Study follow‐up: 27 weeks

Participants

  • Country: USA

  • Setting: multicentre (42 centres)

  • Patients ≥ 18 years; received HD for ≥ 3 mo; were receiving either paricalcitol or doxercalciferol to manage SHPT; historical plasma PTH values between 150 and 800 pg/mL (confirmed during screening); albumin‐corrected serum total calcium concentrations ≥ 8.4 mg/dL. Patients with PTH levels between 300 to 800 pg/mL were considered without regard to serum Ca x P levels, whereas those with PTH levels between 150 to 300 pg/mL were considered only if Ca x P > 55 mg²/dL². After a 3‐wk washout period during which vitamin D therapy was withheld, PTH and calcium levels were measured again on at least 2 occasions. Patients with mean PTH values > 300 pg/mL and mean calcium levels ≥ 8.4 mg/dL qualified for study

  • Number: treatment group (87); control group (86)

  • Mean age ± SD (years): treatment group (57.7 ± SD 14.9); control group (59 ± 12.4)

  • Sex (M/F): treatment group (52/35); control group (45/41)

  • Exclusion criteria: pregnant or nursing; undergone a parathyroidectomy within the previous 3 mo; involved in any other clinical study within the past 30 d; had received cinacalcet previously

Interventions

Treatment group

  • Cinacalcet

  • Low dose vitamin D

  • Duration: 16 weeks titration, 11 weeks maintenance

Control group

  • Vitamin D

Co‐interventions: NS

Outcomes

  • Simultaneously achieved a mean PTH between 150 and 300 pg/mL and a mean Ca x P value < 55 mg²/dL²

  • Achieved KDOQI targets for PTH, calcium, phosphorous, and Ca x P individually

  • Absolute and percentage change from baseline in values for PTH, calcium, phosphorous, and Ca x P

  • Proportion with 30% reduction in PTH

Notes

  • ITT: yes

  • Funding: "The ACHIEVE study (Study ID Number 20050102) and the preparation of this manuscript were funded by Amgen, Inc. The authors wish to thank Nelson Erlick, DPM, MS, on behalf of Amgen Inc. and Jane Mannion, MS, Amgen Inc. for their assistance in the preparation of this manuscript (Ms Mannion is currently employed by Baxter International, Inc.)"

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

NS

Allocation concealment (selection bias)

Unclear risk

NS

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Not used

Blinding of outcome assessment (detection bias)
All outcomes

High risk

Not used

Incomplete outcome data (attrition bias)
All outcomes

High risk

Lost to follow‐up 24% of the patients

Selective reporting (reporting bias)

Low risk

Data available for all included outcomes

Other bias

High risk

Sponsor on authorship

ADVANCE Study 2010

Methods

  • Study design: parallel, open‐label RCT

  • Study duration: NS

  • Study follow‐up: 52 weeks

Participants

  • Country: multinational

  • Setting: multicentre (90 centres)

  • HD ≥ 3 mo; iPTH > 300 pg/mL; serum calcium ≥ 8.4 mg/dL; serum Ca x P > 50 mg²/dL²

  • Number: treatment group (180); control group (180)

  • Mean age ± SD (years): treatment group (61.2 ± 12.6); control group (61.8 ± 12.8)

  • Sex (M/F): treatment group (112/68); control group (95/85)

  • Exclusion criteria: previous cinacalcet treatment; calcium‐free phosphate binding agents; bisphosphonate therapy; lipid lowering within 30 d; atrial fibrillation; coronary artery bypass grafting or stent; valve replacement; heart transplant; pacemaker; aortic aneurysm; parathyroidectomy within 3 mo or in next 6 mo; scheduled kidney transplant; body weight > 136 kg; inability to absorb oral medications; sensitivity to cinacalcet; unstable medical condition

Interventions

Treatment group

  • Cinacalcet

  • Low dose vitamin D

  • Duration: 20‐week dose‐titration phase, 32‐week follow‐up phase

Control group

  • Vitamin D at the same dose prescribed before randomisation

  • Duration: 52 weeks

Co‐interventions

  • Treatment group: vitamin D (75%); phosphate binders (calcium‐based (83%); sevelamer (26%); lanthanum (4%); other (11%))

  • Control group: vitamin D (79%); phosphate binders (calcium‐based (84%); sevelamer (26%); lanthanum (7%); other (8%))

Outcomes

  • % change in CAC score from baseline to week 52

  • Absolute change in CAC score from baseline to week 52

  • Absolute and percentage change in calcification scores for the thoracic aorta, aortic valve and mitral valve from baseline to week 52

  • > 15% progression of CAC from baseline to week 52

  • Absolute and percentage change in PTH, calcium, phosphorous and Ca × P from baseline to the end of study as assessed during weeks 44 to 52 of follow‐up

  • Safety of cinacalcet as measured by the type, frequency and severity of adverse events and their reported relationship to treatment

  • Absolute and percent changes in mean PTH, calcium, phosphorous and Ca × P values from baseline to end of study as assessed at week 44–52 in the efficacy analysis set

Notes

  • ITT: yes

  • Funding: "This study was sponsored by Amgen Inc. J.F. has received speaker and consultant honoraria from Amgen, Genzyme, Shire and has received grant support from Amgen and Fresenius. P.R. has received research grants from Amgen and Genzyme. G.A.B. has received research grants from Amgen, Genzyme, Shire, Novartis, DaVita, and Fresenius; has received fees for expert consultancy and/or advice from Amgen, Genzyme, Shire, Mitsubishi, and Theraclion. P.U.T. has received fees for clinical research, speaking and expert consultancy from Amgen, Shire, Novartis, Roche, Fresenius, Roche, HAS, and Hemotech. G.M.C. has received research funding from Amgen. W.G.G., N.L., G.D. and B.D. are employees and stockholders in Amgen"

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

NS

Allocation concealment (selection bias)

Unclear risk

NS

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Open‐label (http://clinicaltrials.gov/show/NCT00379899)

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NS

Incomplete outcome data (attrition bias)
All outcomes

High risk

Loss to follow‐up 22.2 % patients

Selective reporting (reporting bias)

High risk

Not reported systematically (end of treatment calcium, phoshorous, PTH and adverse events)

Other bias

High risk

Sponsor on authorship

Akiba 2008

Methods

  • Study design: parallel RCT

  • Study duration: April 2003 to October 2003

  • Study follow‐up: 5 weeks

Participants

  • Country: Japan

  • Setting: multicentre (2 centres)

  • Aged 20 to 74 years; serum iPTH ≥ 300 pg/mL, serum calcium 9.0–11.5 mg/dL; treatment with HD for at least 12 weeks before the screening period. Patients receiving vitamin D sterols or phosphate binders were required to be on a stable dose during the screening period. Dialysate calcium concentration and the size of the dialyzer membrane surface area could not be changed during the 14 days before enrolment.

  • Number: treatment group (91 randomised, 79 completed); control group (30)

  • Mean age ± SD (years): treatment group (56.7 ± 9.2; 55.8 ± 7.7; 53.2 ± 7.0); control group (51.8 ± 7.5)

  • Sex (M/F): treatment group (54/25); control group (25/5)

  • Exclusion criteria: severe hepatic diseases; cirrhosis, severe heart failure; uncontrolled hypertension; uncontrolled DM; malignant neoplasm; serious infectious diseases; undergone a parathyroidectomy within 24 weeks before enrolment; parathyroid intervention therapies (percutaneous ethanol injection therapy (PEIT) during the screening period; pregnant or lactating females

Interventions

Treatment group

  • Cinacalcet: 12.5 to 50 mg/d

  • Duration: 3 weeks maintenance, 2 weeks follow‐up

Control group

  • Placebo

Co‐interventions

  • Treatment group: vitamin D (67%); phosphate binders (96%)

  • Control group: vitamin D (70%); phosphate binders (100%)

Outcomes

  • Percentage changes from baseline in serum iPTH levels at the end of dosing (week 3)

  • Percentage changes from baseline in serum calcium, phosphorous, Ca x P and bone metabolism markers (BSAP, osteocalcin, TRACP and NTx) levels at the end of dosing

Notes

  • ITT: per‐protocol analysis was used to analyse efficacy endpoints

  • Three treatment groups were combined

  • Funding: "This study was supported by Kirin Brewery. Drs Akizawa, Tsukamoto, Uchida, Iwasaki and Koshikawa are scientific advisors for Kirin Brewery"

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Central computerised system

Allocation concealment (selection bias)

Unclear risk

NS

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

"Cinacalcet and placebo tablets were identical in appearance in order to maintain the double‐blind status of the study."

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

"All laboratory determinations, except for hematological assessments, were performed at a central laboratory"

Incomplete outcome data (attrition bias)
All outcomes

High risk

Per‐protocol analysis was used to analyse efficacy endpoints. 14.2% lost to follow‐up in the active arm. 10.7% lost to follow‐up in total

Selective reporting (reporting bias)

Low risk

All the prespecified outcomes were reported

Other bias

High risk

Authors are scientific advisors for sponsor

Block 2004a

Methods

  • Study design: parallel RCT

  • Study duration: December 2001 to January 2003

  • Study follow‐up: 26 weeks

Participants

  • Country: multinational

  • Setting: multicentre (125 centres)

  • Medically stable patients with secondary hyperparathyroidism; ≥ 18 years; treated with thrice‐weekly HD for at least three mo; mean plasma PTH of at least 300 pg/mL; established by 3 measurements obtained within a 30‐day screening period. Dialysate calcium levels remained unchanged throughout the study.

  • Number: treatment group (371); control group (370)

  • Mean age ± SD (years): treatment group (54 ± 14); control group (55 ± 15)

  • Sex (M/F): treatment group (226/145); control group (229/141)

  • Exclusion criteria: evidence of cancer; active infection; diseases known to cause hypercalcaemia; serum Ca < 8.4 mg/dL corrected for albumin; receiving drugs such as flecainide, thioridazine, and most tricyclic antidepressants

Interventions

Treatment group

  • Cinacalcet: 30 to 180 mg/d

  • Duration: 12 weeks titration, 14 weeks maintenance

Control group

  • Placebo

Co‐interventions

  • Treatment group: vitamin D (66%); phosphate binders (92%)

  • Control group: vitamin D (67%); phosphate binders (93%)

Outcomes

  • Mean PTH ≤ 250 pg/mL

  • Reduction from base line of at least 30% in mean PTH levels

  • Percent change in the values for PTH, calcium, phosphorous, Ca x P

Notes

  • Stop/endpoints: iPTH < 250 pg/mL

  • ITT: no

  • Pooled data from 2 studies

  • Funding: "Supported by Amgen"

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

NS

Allocation concealment (selection bias)

Unclear risk

NS

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded study

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NS

Incomplete outcome data (attrition bias)
All outcomes

High risk

Loss to follow‐up 22%

Selective reporting (reporting bias)

Low risk

All the prespecified outcomes were reported

Other bias

High risk

Pooled data from 2 studies; statistical analyses and data interpretation by sponsor; data held by sponsor; editorial assistance from sponsor

Charytan 2005

Methods

  • Study design: parallel RCT

  • Study duration: June 2002 and March 2003

  • Study follow‐up: 18 weeks

Participants

  • Country: USA and Canada

  • Setting: multicentre (16 centres)

  • Men and women, ≥ 18 years with CKD and SHPT but were not receiving dialysis; GFR of 15 to 50 mL/min/1.73 m²; one iPTH < 130 pg/mL; serum Ca ≥ 9.0 mg/dL

  • Number: treatment group (27); control group (27)

  • Mean age ± SD (years): treatment group (60.6 ± 15.6); control group (61.9 ± 15.1)

  • Sex (M/F): treatment group (16/11); control group (22/5)

  • Exclusion criteria: any unstable medical condition; pregnant or lactating; undergone parathyroidectomy or experienced MI in the previous 3 months; kidney transplantation at any time; changed vitamin D therapy in the previous 30 days; were likely to begin dialysis therapy or receive a kidney transplant within 18 weeks

Interventions

Treatment group

  • Cinacalcet: 30 to 180 mg/d

  • Duration: 12 weeks titration, 6 weeks maintenance

Control group

  • Placebo: 30 to 180 mg/d

  • Duration: 12 weeks titration, 6 weeks maintenance

Co‐interventions

  • Treatment group: vitamin D (22%); phosphate binders (37%)

  • Control group: vitamin D (33%); phosphate binders (48%)

Outcomes

  • ≥ 30% reduction from baseline in mean iPTH

  • Percentage change in mean iPTH within each treatment group (efficacy)

  • Collection of adverse events and laboratory parameters (safety)

Notes

  • ITT: yes

  • Funding: "Supported in part by a grant from Amgen Inc. WL, PSK, and LCM are employees of Amgen Inc"

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

NS

Allocation concealment (selection bias)

Low risk

Centralised interactive voice‐response system

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded study

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NS

Incomplete outcome data (attrition bias)
All outcomes

High risk

Loss to follow‐up 30% of patients

Selective reporting (reporting bias)

Low risk

All the prespecified outcomes were reported

Other bias

High risk

Sponsor on authorship

Chonchol 2009

Methods

  • Study design: parallel RCT

  • Study duration: December 2004 to August 2006

  • Study follow‐up: 32 weeks

Participants

  • Country: multinational

  • Setting: multicentre (73 centres)

  • Adults with an iPTH ≥ 100 pg/mL (CKD stage 3) or ≥ 160 pg/mL (CKD stage 4); eGFR 15 to 59 mL/min/1.73 m²; albumin‐corrected serum calcium concentration ≥ 9.0 mg/dL

  • Number: treatment group (302); control group (102)

  • Mean age ± SD (years): treatment group (64.7 ± 13.3); control group (66.2 ± 12.2)

  • Sex (M/F): treatment group (177/125); control group (60/42)

  • Exclusion criteria: kidney transplantation; pregnancy; lactation; laboratory evidence of primary hyperparathyroidism; unstable medical condition; participation in a previous cinacalcet clinical study; likelihood of dialysis or scheduled for kidney transplantation within 28 weeks after day 1; MI within 3 months before day 1; participation in another investigational study; prior treatment with cinacalcet; change in active vitamin D sterol treatment in the previous 30 days

Interventions

Treatment group

  • Cinacalcet: 30 to 180 mg/d

  • Duration: 16 weeks titration, 16 weeks maintenance

Control group

  • Placebo

Co‐interventions

  • Treatment group: vitamin D (21%); phosphate binders (19%)

  • Control group: vitamin D (21%); phosphate binders (18%)

Outcomes

  • Mean ≥ 30% decrease in iPTH level

  • iPTH ≤ 70 pg/mL (CKD stage 3) or ≤ 110 pg/mL (CKD stage 4)

  • Mean percentages of change in iPTH levels from baseline

  • Adverse events

  • Changes in haematology, clinical chemistry and urine calcium and phosphorous results

Notes

  • ITT: no

  • Funding: "The writing of this manuscript was supported by Amgen Inc; see Financial Disclosure for further information." "This trial (20000178) was sponsored by Amgen Inc, which markets cinacalcet. Dr Chonchol is a member of advisory boards for Amgen; Dr Locatelli is a member of advisory boards for Amgen‐Dompé, Shire, and Mitsubishi; Dr Charytan receives research and/or consultation support from Amgen; Dr de Francisco is a clinical advisor for Amgen and lectures for Amgen, Roche, Jansen Cilag, and Abbott; Dr Jolly is a stockholder of Amgen; Drs Albizem and Mix and Ms Kubo are employees of and stockholders of Amgen; and Dr Block is an advisor for Amgen and has received research support from Amgen."

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

NS

Allocation concealment (selection bias)

Low risk

Interactive voice‐response system

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Blinded study

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NS

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Loss to follow‐up 3% of patients

Selective reporting (reporting bias)

Low risk

All the prespecified outcomes were reported

Other bias

High risk

Sponsor on authorship; sponsor involved in writing manuscript

El Shafey 2011

Methods

  • Study design: parallel RCT

  • Study duration: July 2009 to August 2010

  • Study follow‐up: 36 weeks

Participants

  • Country: Kuwait; Saudi Arabia

  • Setting: multicentre (2 centres)

  • Adults ≥ 18 years; ESKD with SHPT; receiving maintenance HD 3 times/week for ≥ 3 months; iPTH ≥ 31.8 pmol/L; albumin‐corrected serum calcium ≥ 2.1 mmol/L; no more than 20% of the study population could have iPTH levels exceeding 84.8 pmol/L

  • Number: treatment group (55); control group (27)

  • Mean age ± SD (years): treatment group (51.5 ± 12.7); control group (51.8 ± 15)

  • Sex (M/F): treatment group (27/28); control group (14/13)

  • Exclusion criteria: any unstable medical condition; breastfeeding; experienced a MI within 3 month of study day 1; undergone a parathyroidectomy within 6 month of study day 1; gastrointestinal disorder associated with impaired absorption of oral medications or an inability to swallow tablets; received vitamin D therapy for < 21 d; change in prescribed vitamin D brand or dose within 21 d before study day 1; enrolled in other studies; previously enrolled or participated in other cinacalcet clinical studies

Interventions

Treatment group

  • Cinacalcet: 30 to 180 mg/d

  • Duration: 12 weeks titration, 24 weeks maintenance

Control group

  • Conventional therapy

Co‐interventions

  • Treatment group: vitamin D (50%); phosphate binders (86%)

  • Control group: vitamin D (52%); phosphate binders (89%)

Outcomes

  • Mean iPTH ≤ 31.8 pmol/L

  • Both mean Ca x P < 4.44 mmol²/L² and iPTH ≤ 31.8 pmol/L

  • Mean calcium < 2.37 mmol/L

  • Mean phosphorous < 1.78 mmol/L

  • Mean Ca x P < 4.44 mmol²/L²

  • Adverse events

  • Changes in safety laboratory parameters (including clinical chemistry and haematology)

Notes

  • ITT: no

  • Funding: NS

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

NS

Allocation concealment (selection bias)

Unclear risk

NS

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Not blinded

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NS

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Loss to follow‐up 5% of patients

Selective reporting (reporting bias)

Low risk

All the prespecified outcomes were reported

Other bias

High risk

Uneven comparisons

EVOLVE study 2007

Methods

  • Study design: parallel RCT

  • Study duration: 22 August 2006, to 31 January 2008

  • Study follow‐up: treatment group (21.2 months); control group (17.5 months)

Participants

  • Country: multinational (USA, Canada, Argentina, Brazil, Mexico, Australia, Austria, Belgium, Denmark, France, Germany, Hungary, Ireland, Italy, Netherlands, Poland, Portugal, Russia, Spain, Sweden, Switzerland, UK)

  • Setting: multicentre (approx. 500 centres)

  • Men or women ≥18 years of age at screening; treated with maintenance HD 3 times/wk for ≥ 3 months before randomisation; PTH ≥ 300 pg/mL; serum calcium ≥ 8.4 mg/dL; Ca x P ≥45 mg²/dL²; available during the follow‐up phase of the study; agree to be followed for study endpoints until the end of study; appropriate written informed consent must be obtained.

  • Number: treatment group (1948); control group (1935)

  • Mean age ± SD: 54 ± 14 years

  • Sex (M/F): treatment group (1140/808); control group (1167/768)

  • Exclusion criteria: unstable medical condition; parathyroidectomy; severe concomitant disease, including life‐threatening malignancy or acquired immune deficiency syndrome, or any other life‐threatening concomitant disease; received therapy with cinacalcet within 3 months of randomisation; hospitalization within 12 weeks of randomisation for any of the following events (MI, unstable angina, heart failure, peripheral vascular disease, stroke; history of seizure within 12 weeks prior to randomisation); scheduled date for kidney transplant from a known living donor; anticipated parathyroidectomy within 6 months after randomisation; currently enrolled in or has not yet completed at least 30 days since ending other investigational device or drug study(s); receiving other investigational agent(s); known sensitivity or intolerance to any of the products to be administered; any kind of disorder that compromises the ability of the subject to give written informed consent and/or to comply with study procedures; pregnant; breast feeding; child‐bearing potential and not using adequate contraceptive precautions

Interventions

Treatment group

  • Cinacalcet: 30 to 180 mg/d

  • Duration: 21.2 months

Control group

  • Placebo

  • Duration: 17.5 months

Co‐interventions

  • Treatment group: vitamin D (59.3%); phosphate binders (87.8%)

  • Control group: vitamin D (59.6%); phosphate binders (89%)

Outcomes

  • Composite endpoint of time to death or first nonfatal cardiovascular event (MI, hospitalisation for unstable angina, heart failure, or a peripheral vascular event)

  • Time to individual components of primary composite endpoint

  • Death from cardiovascular causes

  • Stroke

  • Bone fracture

  • Parathyroidectomy

Notes

  • ITT: yes

  • Funding: "This study was funded by Amgen, Inc and led by an executive committee composed of academic members, two sponsor members (nonvoting), and statisticians. The executive committee oversaw the design, conduct, and all analyses. Data were collected by the sponsor and shared with the executive committee throughout the study and after unblinding. The analysis was performed by the sponsor and confirmed by an independent biostatistician at Stanford University School of Medicine. The sponsor provided the active medication and matching placebo. The lead author wrote the first draft of the manuscript, and the executive committee was responsible for data interpretation and manuscript completion. The sponsor reviewed the manuscript, but decisions about the final manuscript were made by the lead author and academic members of the executive committee only."

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Generated by Amgen

Allocation concealment (selection bias)

Low risk

Interactive voice‐response system

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Double‐blinded

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Blinded

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Loss to follow‐up 7.9% of patients

Selective reporting (reporting bias)

Low risk

All the prespecified outcomes were reported

Other bias

High risk

Sponsor on authorship; sponsor involved in writing manuscript; sponsor held data and analysed data

Fukagawa 2008

Methods

  • Study design: parallel RCT

  • Study duration: April to December 2004

  • Study follow‐up: 14 weeks

Participants

  • Country: Japan

  • Setting: multicentre (29 centres)

  • Patients > 20 years of age with ESRD and SHPT who were undergoing HD 3 times/wk for at least 16 weeks and were in a medically stable condition; serum iPTH level ≥300 pg/mL both at 1 and 2 weeks prior to the cinacalcet administration; serum calcium level ≥ 9.0 mg/dL at 1 week prior to the cinacalcet administration

  • Number: treatment group (72); control group (71)

  • Mean age ± SD (years): treatment group (54.7 ± 11); control group (55.7 ± 11.7)

  • Sex (M/F): treatment group (40/32); control group (37/34)

  • Exclusion criteria: parathyroidectomy within 24 weeks prior to the treatment; percutaneous ethanol injection therapy into the parathyroid gland during the 4 weeks’ screening period; severe impairment of hepatic function; severe hypertension; uncontrolled DM; cancer; severe infection; severe cardiac failure

Interventions

Treatment group

  • Cinacalcet: 30 to 180 mg/d

  • Duration: 14 weeks

Control group

  • Placebo

Co‐interventions

  • Treatment group: vitamin D (87.5%); phosphate binders (93.1%)

  • Control group: vitamin D (88.7%); phosphate binders (95.8%)

Outcomes

  • Percentage with serum iPTH levels ≤ 250 pg/mL at the end of the dosing

  • Adverse events

  • Laboratory variables

  • Vital signs

Notes

  • ITT: yes

  • Funding: "This study was supported by Kirin Pharma Co., Ltd."

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Centralised computer system

Allocation concealment (selection bias)

Unclear risk

NS

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Double‐blinded

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NS

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Loss to follow‐up 2.8% of patients

Selective reporting (reporting bias)

Low risk

All the prespecified outcomes were reported

Other bias

High risk

Study sponsored by Kirin Parma Co. LTD

Goodman 2000

Methods

  • Study design: parallel RCT

  • Study duration: NS

  • Study follow‐up: 24 days

Participants

  • Country: USA

  • Setting: multicentre

  • Medically stable individuals ≥ 18 years undergoing HD 3 times/wk for at least 3 months with biochemical evidence of secondary hyperparathyroidism as judged by serum PTH levels between 300 and 1200 pg/mL; calcium levels > 9.0 mg/dL; serum phosphorous levels > 3.0 mg/dL; serum aluminium levels < 40 mg/L; serum CO2 levels > 15 mEq/L; serum potassium concentrations < 6.2 mEq/L; HCT values > 30%; serum ferritin levels > 100 ng/mL; transferrin saturation values > 20%; urea reduction rate ≥ 65% and/or measured Kt/V values > 1.2.

  • Number: treatment group (16); control group (5 randomised, 4 analysed)

  • Mean age ± SD (years): treatment group (48.6 ± 12.4); control group (54.7 ± 16.8)

  • Sex (M/F): treatment group (13/3); control group (1/3)

  • Exclusion criteria: women of childbearing age unless they were using effective contraceptive measures or had previously been rendered sterile surgically; serum levels of hepatic transaminases or bilirubin were more than twice the upper limit of normal or if they were using medication such as selective serotonin reuptake inhibitors, tricyclic antidepressants, or B‐adrenergic blocking agents that are metabolized extensively by the P450 pathway; history of seizures; malignancy; hyperthyroidism; granulomatous diseases that could cause hypercalcaemia; MI within the previous 6 months; corrected QT interval (QTc) on electrocardiogram that exceeded 450 milliseconds

Interventions

Treatment group

  • R‐568: 100 mg/d

  • Duration: 15 days maintenance

Control group

  • Placebo

Co‐interventions

  • Treatment group: vitamin D (38%); phosphate binders (31%)

  • Control group: vitamin D (50%); phosphate binders (50%)

Outcomes

  • Plasma PTH

  • Blood‐ionized calcium

  • Pharmacokinetic data

  • Adverse effects

Notes

  • ITT: no

  • Funding: "This work was supported by Amgen, Inc., and by USPHS grants RR‐00865 and DK‐52905"

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

NS

Allocation concealment (selection bias)

Unclear risk

NS

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Double‐blinded

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NS

Incomplete outcome data (attrition bias)
All outcomes

High risk

Loss to follow‐up 38% of patients

Selective reporting (reporting bias)

High risk

Not reported systematically (end of treatment calcium, phoshorous, PTH and adverse events)

Other bias

High risk

Sponsor on authorship

Goodman 2002

Methods

  • Study design: parallel RCT

  • Study duration: NS

  • Study follow‐up: 16 days

Participants

  • Country: USA

  • Setting: multicentre

  • Patients ≥ 18 years; medically stable, and had been treated for at least 3 months with thrice‐weekly HD with evidence of secondary hyperparathyroidism as judged by two plasma PTH determinations obtained at least a week apart within 21 d of the initial dose of AMG‐073 that were between 250 and 1500 pg/mL; serum total calcium values of ≥ 9.0 mg/dL after correcting for serum albumin concentrations; serum phosphorous levels of ≥ 2.5 mg/dL; serum aluminium levels < 40 ug/L; Hb level ≥ 10 g/dL or a blood HCT ≥ 30%; chest radiograph within the past 6 months showing no evidence of active parenchymal disease; body mass index between 15 and 40 kg/m²

  • Number: treatment group (23); control group (7)

  • Mean age ± SD: 46 ± 16 years

  • Sex (M/F): NS

  • Exclusion criteria: women of childbearing age unless they had previously been rendered sterile surgically for other medical reasons; serum levels of hepatic transaminases or bilirubin were more than twice the upper limit of normal; history of seizures within the past 12 months; malignancy within the past 5 years; hyperparathyroidism; MI within the previous 6 months a cardiac ventricular rhythm disturbance requiring active treatment; a gastrointestinal disorder that could affect the absorption of drugs given orally; granulomatous diseases that could cause hypercalcaemia

Interventions

Treatment group

  • AMG‐073: 10 to 50 mg/d

  • Duration: 8 days maintenance

Control group

  • Placebo

Co‐interventions: NS

Outcomes

  • Serum PTH

  • Serum calcium

  • Dose response

Notes

  • ITT: no

  • Funding: "This work was supported by Amgen Inc. and by USPHS grants DK‐52905, DK‐60107, and RR‐00865"

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

NS

Allocation concealment (selection bias)

Unclear risk

NS

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Double blinded

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NS

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No patients lost to follow‐up

Selective reporting (reporting bias)

Low risk

All the prespecified outcomes were reported

Other bias

High risk

Sponsor on authorship

Harris 2004

Methods

  • Study design: parallel RCT

  • Study duration: NS

  • Study follow‐up: 12 weeks

Participants

  • Country: USA

  • Setting: multicentre (2 centres)

  • Medically stable patients with serum calcium levels corrected for albumin concentration ≥ 8.4 mg/dL; serum phosphorous levels ≥ 3.0 mg/dL

  • Number: treatment group (17); control group (5)

  • Mean age ± SD (years): treatment group (48.5 ± 10.4); control group (48 ± 13.1)

  • Sex (M/F): treatment group (14/3); control group (4/1)

  • Exclusion criteria: NS

Interventions

Treatment group

  • Cinacalcet: 25 to 300 mg/d

  • Duration: 12 weeks

Control group

  • Placebo

Co‐interventions

  • Treatment group: vitamin D (71%); phosphate binders (100%)

  • Control group: vitamin D (60%); phosphate binders (80%)

Outcomes

  • Pharmacodynamic data at doses > 100 mg

  • Adverse effects

Notes

  • ITT: no

  • Funding: "From Pharmacokinetics and Drug Metabolism, Early Development, and Biostatistics, Amgen Inc, Thousand Oaks, CA; Orlando Clinical Research Center, Orlando, FL; and Clinical Research Center, New Orleans, LA"

  • Not included in meta‐analyses

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

NS

Allocation concealment (selection bias)

Unclear risk

NS

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Double‐blinded

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NS

Incomplete outcome data (attrition bias)
All outcomes

High risk

Loss to follow‐up 59.1% of patients

Selective reporting (reporting bias)

High risk

Not reported systematically (end of treatment calcium, phosphorous, PTH and adverse events)

Other bias

High risk

Sponsor on authorship

IMPACT SHPT Study 2012

Methods

  • Study design: parallel, open‐label RCT

  • Study duration: NS

  • Study follow‐up: 28 weeks

Participants

  • Country: multinational

  • Setting: multicentre (89 centres)

  • Eligible patients were aged ≥ 8 years with Stage 5 CKD receiving maintenance HD 3 times/wk for at least 3 months before screening and were to continue HD during the study; serum iPTH 130 to 700 pg/mL; total alkaline phosphatase ≥ 0 U/L; calcium ≤ 10.0 mg/dL; Ca x P ≤ 5 mg²/dL² for US centres or ≤ 70 mg²/dL² for non‐US centres; iPTH 300–800 pg/mL; calcium 8.4 to 10.0 mg/ dL; phosphorous ≤ 6.5 mg/dL

  • Number: treatment group (134); control group (134)

  • Mean age ± SD (years): treatment group‐IV (59.9 ± 12.0); treatment group‐oral (65.1 ± 12.5); control group‐IV (61.2 ± 12.7); control group‐oral (65.7 ± 13.5)

  • Sex (M/F): treatment group‐IV (38/26); treatment group‐oral (43/27); control group‐IV (38/26); oral group‐oral (49/23)

  • Exclusion criteria: allergic reaction or significant sensitivity to any study drug; expected daily requirement of > 2.0 g of oral elemental calcium; previous parathyroidectomy; chronic gastrointestinal disorders; clinically significant liver disease and use of known inhibitors or inducers of cytochrome P450 3A or of drugs metabolized by cytochrome P450 2D6 within 2 weeks before study drug administration

Interventions

Treatment group

  • Cinacalcet

  • Low dose vitamin D

  • Duration: 28 weeks

Control group

  • Vitamin D

Co‐interventions: NS

Outcomes

  • Mean iPTH value of 150 to 300 pg/mL during weeks 21 to 28

  • Achieved ≥ 30% or ≥ 50% reduction from baseline in iPTH

  • Hypocalcaemia (mean calcium < 8.4 mg/dL) during weeks 21 to 28

  • Hypercalcaemia (mean calcium > 10.5 mg/dL) during weeks 21 to 28

  • BSAP

  • Alkaline phosphatase

Notes

  • ITT: yes

  • Funding: "The IMPACT SHPT study was funded by Abbott Laboratories Inc. Writing and editorial assistance, funded by Abbott Laboratories Inc., was provided by Roland Tacke, PhD, Marsha Hall and Colleen Hedge of Scientific Connexions, Newtown, PA, USA"

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

Generated by Clinical Statistics department of Abbott

Allocation concealment (selection bias)

Low risk

Interactive voice‐response system

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Not blinded

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NS

Incomplete outcome data (attrition bias)
All outcomes

High risk

Loss to follow‐up 24.3% of patients

Selective reporting (reporting bias)

Low risk

All the prespecified outcomes were reported

Other bias

High risk

Sponsor on authorship; sponsor involved in writing manuscript; sponsor held data and analysed data

Lindberg 2003

Methods

  • Study design: parallel RCT

  • Study duration: NS

  • Study follow‐up: 18 weeks

Participants

  • Country: USA, Canada

  • Setting: multicentre (23 centres)

  • Patients ≥ 18 years, treated for at least 3 mo with HD; PTH levels ≥ 300 pg/mL despite receiving standard of care (phosphate binders and/or vitamin D sterols); serum calcium corrected for serum albumin ≥ 8.8 mg/dL and < 11.0 mg/dL; serum phosphorous ≥ 2.5 mg/dL; Ca x P < 70 mg²/dL². Patients receiving vitamin D sterols were required to be on a stable dose for at least 21 days before enrolment; dialysate calcium concentration and calcium supplements/oral phosphate binders dose could not be changed during the 7 days before enrolment

  • Number: treatment group (39); control group (39)

  • Mean age ± SD (years): treatment group (52.7 ± 16.4); control group (48.8 ± 15.6)

  • Sex (M/F): treatment group (24/15); control group (22/17)

  • Exclusion criteria: medically unstable; evidence of an active infectious or malignant process or diseases known to cause hypercalcaemia; Hb concentration < 9.0 g/dL or a HCT < 27%; liver transaminases and bilirubin levels more than twice the upper limit of normal

Interventions

Treatment group

  • AMG‐073: 10 to 50 mg/d

  • Duration: 12 weeks titration, 6 weeks maintenance

Control group

  • Placebo

Co‐interventions

  • Treatment group: vitamin D (67%); phosphate binders (87%)

  • Control group: vitamin D (62%); phosphate binders (87%)

Outcomes

  • Reduction in PTH ≥ 30% during the maintenance phase

  • Mean percent change from baseline for PTH, serum calcium, phosphorous, and Ca x P during the maintenance phase

  • Adverse events

  • Laboratory variables (haematology and biochemistry)

  • Vital signs

Notes

  • ITT: no

  • Funding: "Funding for this study was provided by Amgen Inc"

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

NS

Allocation concealment (selection bias)

Unclear risk

NS

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Double‐blinded

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NS

Incomplete outcome data (attrition bias)
All outcomes

High risk

Loss to follow‐up 14.1% of patients

Selective reporting (reporting bias)

High risk

Not reported systematically (end of treatment calcium, phosphorous, PTH and adverse events)

Other bias

High risk

Sponsor on authorship

Lindberg 2005

Methods

  • Study design: parallel RCT

  • Study duration: May 2002 to March 2003

  • Study follow‐up: 26 weeks

Participants

  • Country: multinational

  • Setting: multicentre (60 centres)

  • Age ≥18 years; mean of two plasma iPTH values ≥ 300 pg/mL; mean of two serum calcium values ≥ 8.4 mg/dL during the screening phase; treatment with HD, continuous ambulatory PD, or automated PD for at least 1 mo before beginning study medication; patients who were receiving vitamin D therapy must have been treated with a stable dose for at least 30 d before enrolment

  • Number: treatment group (294); control group (101)

  • Mean age ± SD (years): treatment group (51.8 ± 14.0); control group (53.5 ± 13.9)

  • Sex (M/F): treatment group (181/113); control group (64/37)

  • Exclusion criteria: an unstable medical condition; undergone parathyroidectomy; MI within 3 mo before the study began

Interventions

Treatment group

  • Cinacalcet: 30 to 180 mg/d

  • Duration: 16 weeks titration, 10 weeks maintenance

Control group

  • Placebo

Co‐interventions

  • Treatment group: vitamin D (65%); phosphate binders (NS)

  • Control group: vitamin D (69%); phosphate binders (NS)

Outcomes

  • Mean iPTH level ≤ 250 pg/mL

  • Reduction in iPTH of at least 30% from baseline

  • Mean percentage changes from baseline for iPTH, serum calcium, phosphorous, and Ca x P

  • Mean iPTH ≤ 300 pg/mL or reductions in iPTH of a least 20%, 40%, or 50% from baseline

  • Ca x P < 55 mg²/dL²

  • Mean reduction in Ca x P of at least 5 or 10 mg²/dL²

Notes

  • ITT: yes

  • Funding: "This study was supported by Amgen Inc. Holly Brenza Zoog assisted in the preparation of the manuscript."

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Programmatic algorithm

Allocation concealment (selection bias)

Low risk

Interactive voice‐response system

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Double‐blinded

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NS

Incomplete outcome data (attrition bias)
All outcomes

High risk

Loss to follow‐up 25.3% of patients

Selective reporting (reporting bias)

High risk

Not reported systematically (end of treatment calcium, phosphorous, PTH and adverse events)

Other bias

High risk

Sponsor on authorship

Malluche 2008

Methods

  • Study design: parallel RCT

  • Study duration: October 2001 to May 2003

  • Study follow‐up: 52 weeks

Participants

  • Country: multinational

  • Setting: multicentre (17 centres)

  • Medically stable patients ≥ 18 years who had received HD for ≥ 1 month with biochemical evidence of elevated PTH levels; albumin‐adjusted serum calcium concentration ≥ 8.4 mg/dL; either Hb level > 9.0 g/dL or a HCT value > 27%; patients receiving vitamin D sterols had to have been on a constant dose for ≥ 30 days before beginning the study

  • Number: treatment group (19); control group (13)

  • Mean age ± SD (years): treatment group (50.3 ± 13.3); control group (51.5 ± 14.1)

  • Sex (M/F): treatment group (12/7); control group (9/4)

  • Exclusion criteria: received bisphosphonate or fluoride during the preceding 90 days

Interventions

Treatment group

  • Cinacalcet: 30 to 180 mg/d

  • Duration: 24 weeks titration, 28 weeks maintenance

Control group

  • Placebo

Co‐interventions

  • Treatment group: vitamin D (47%); phosphate binders (100%)

  • Control group: vitamin D (54%); phosphate binders (77%)

Outcomes

  • Interval changes in activation frequency, bone formation rate/bone surface, number of osteoblasts and osteoclasts/bone perimeter, fibrosis surface/bone surface and woven osteoid surface/bone surface

  • Absolute and percentage changes from baseline in iPTH, BSAP, NTx and Ca x P

Notes

  • ITT: no

  • Funding: "This study was supported by Amgen Inc (Study 20010141)"

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer generated

Allocation concealment (selection bias)

Low risk

Interactive voice‐response system

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Double‐blinded

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NS

Incomplete outcome data (attrition bias)
All outcomes

High risk

Loss to follow‐up 31.3% of patients

Selective reporting (reporting bias)

High risk

Not reported systematically (end of treatment calcium, posphorous, PTH and adverse events)

Other bias

High risk

Sponsor authorship

OPTIMA Study 2008

Methods

  • Study design: parallel, open‐label RCT

  • Study duration: NS

  • Study follow‐up: 23 weeks

Participants

  • Country: Europe

  • Setting: multicentre (111 centres)

  • Patients ≥ 18 years with ESKD with SHPT and had required maintenance dialysis for ≥ 1 mo; iPTH ≥ 300 pg/mL and < 800 pg/mL; bio‐intact PTH ≥150 pg/mL and < 410 pg/mL; albumin‐corrected serum calcium ≥ 8.4 mg/dL

  • Number: treatment group (368); control group (184)

  • Mean age ± SD (years): treatment group (58.5 ± 14.5); control group (58.3 ± 14.5)

  • Sex (M/F): treatment group (224/144); control group (117/67)

  • Exclusion criteria: any unstable medical condition; breastfeeding; MI within 3 mo of study day 1; parathyroidectomy within 6 mo of study day 1; gastrointestinal disorder associated with impaired absorption of oral medications or an inability to swallow tablets; patients who received vitamin D therapy for < 21 d or had a change in their prescribed vitamin D brand or dose within 21 d before study day 1; enrolled in other studies; previously enrolled or participated in other cinacalcet clinical studies

Interventions

Treatment group

  • Cinacalcet: 30 to 180 mg/d

  • Duration: 16 weeks titration, 7 weeks maintenance

Control group

  • Placebo

Co‐interventions

  • Treatment group: vitamin D (68%); phosphate binders (92%)

  • Control group: vitamin D (68%); phosphate binders (90%)

Outcomes

  • Mean iPTH ≤ 300 pg/mL

  • Both mean Ca x P < 55 mg²/dL² and iPTH ≤ 300 pg/mL

  • Mean Ca × P < 55 mg²/dL²

  • Man calcium < 9.5 mg/dL

  • Mean phosphorous < 5.5 mg/dL

Notes

  • ITT: yes

  • Funding: "This study was sponsored by Amgen Inc."

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

NS

Allocation concealment (selection bias)

Unclear risk

NS

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Not blinded

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NS

Incomplete outcome data (attrition bias)
All outcomes

High risk

Loss to follow‐up 21.9% of patients

Selective reporting (reporting bias)

Low risk

All the prespecified outcomes were reported

Other bias

High risk

Sponsor on authorship

Quarles 2003a

Methods

  • Study design: parallel RCT

  • Study duration: NS

  • Study follow‐up: 18 weeks

Participants

  • Country: USA

  • Setting: multicentre (17 centres)

  • Patients ≥ 18 years treated for at least 3 mo with HD and had uncontrolled SHPT (mean PTH ≥ 300 pg/mL, despite availability of standard care (phosphate binders and/or vitamin D sterols)); serum calcium ≥ 8.8 mg/dL and < 11.0 mg/dL; serum phosphorous ≥ 2.5 mg/dL; Ca x P < 70 mg²/dL²; patients receiving vitamin D sterols must have been on a stable dose for at least 21 d before enrolment; dialysis calcium concentration, the dose of any supplements, and the dose of oral phosphate binders must not have been changed during the 7 d before enrolment

  • Number: treatment group (36); control group (35)

  • Mean age ± SD (years): treatment group (49.6 ± 8.5); control group (47.9 ± 14.2)

  • Sex (M/F): treatment group (27/9); control group (17/18)

  • Exclusion criteria: medically unstable; evidence of an active infectious; malignant process; diseases known to cause hypercalcaemia; Hb concentration < 9.0 g/dL or a HCT < 27%; liver transaminases and bilirubin concentrations more than twice the upper limit of normal

Interventions

Treatment group

  • AMG‐073: 25 to 100 mg/d

  • Duration: 12 weeks titration, 6 weeks maintenance

Control group

  • Placebo

Co‐interventions

  • Treatment group: vitamin D (61%); phosphate binders (100%)

  • Control group: vitamin D (69%); phosphate binders (94%)

Outcomes

  • Mean reduction in PTH of ≥ 30% during the maintenance phase

Notes

  • Stop/end point: iPTH reduction = 30%

  • ITT: yes

  • Funding: "Funding for this study was provided by Amgen Inc."

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

NS

Allocation concealment (selection bias)

Low risk

Interactive voice‐response system

Blinding of participants and personnel (performance bias)
All outcomes

Low risk

Double blinded

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

NS

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Loss to follow‐up 8.5% of patients

Selective reporting (reporting bias)

High risk

Not reported systematically (end of treatment calcium, phosphorous, PTH and adverse events)

Other bias

High risk

Sponsor on authorship

BSAP ‐ bone‐specific alkaline phosphatase; Ca x P ‐ calcium‐phosphorous product; CAC ‐ coronary artery calcification score; DM ‐ diabetes mellitus; ESKD ‐ end‐stage kidney disease; GFR ‐ glomerular filtration rate; Hb ‐ haemoglobin; HCT ‐ haematocrit; HD ‐ haemodialysis; iPTH ‐ intact parathyroid hormone; ITT ‐ Intention‐to‐treat; MI ‐ myocardial infarction; NA ‐ not available; NS ‐ not stated; NTx ‐ cross‐linked N‐telopeptides of type I collagen; PTH ‐ parathyroid hormone; RCT ‐ randomised controlled trial; SHPT ‐ secondary hyperparathyroidism; TRACP ‐ tartrate‐resistant acid phosphatase

Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Al‐Hilali 2011

Not appropriate intervention

Coburn 2000a

Not appropriate outcome

CONTROL Study 2006

Not RCT

Cunningham 2003

Observational extension study

Cunningham 2005

Observational extension study

de Francisco 2005

Not RCT

Harris 2003

Not appropriate outcome

Kaperonis 2012

Not RCT

Moe 2003a

Not RCT

Moe 2005

Not RCT

Moe 2005b

Not RCT

Padhi 2003

Not CKD population

Pahl 1996

Not intervention

Quarles 2003

Not RCT

Schaefer 2008

Not intervention

Sezer 2012

Not intervention

TARGET Study 2008

Not RCT

CKD ‐ chronic kidney disease; RCT ‐ randomised controlled trial

Characteristics of studies awaiting assessment [ordered by study ID]

Coburn 2003

Methods

Randomised double‐blind placebo‐controlled study

Participants

Patients with CKD not treated with dialysis (GFR 15 to 50 mL/min) and intact PTH levels > 130 ng/mL

Interventions

Cinacalcet 30 to 180 mg/d titrated to obtain a ≥ 30% reduction in intact PTH levels

Outcomes

Mean change in PTH, per cent with reduced PTH ≥ 30%, calcium and phosphorous levels

Notes

Unclear whether an additional report of Charytan 2005

Drueke 2001a

Methods

Placebo controlled RCTs (3)

Participants

Dialysis patients

Number: AMG‐073 (141); placebo (74)

Interventions

AMG‐073 (50 to 100 mg/d)

Outcomes

Ca x P; mean iPTH

Notes

Abstract only; states combined data of the first 12 weeks of 3 studies ‐ unable to determine which 3 studies

Fournier 2004a

Methods

Placebo controlled RCTs (3)

Participants

Dialysis patients with iPTH ≥ 300 pg/mL

Number: 955

Interventions

Cinacalcet 30 to 180 mg/d

Outcomes

Ca x P; mean iPTH

Notes

Abstract only; states combined data of 3 studies ‐ unable to determine which 3 studies

UPen 2004a

Methods

Randomised double‐blinded placebo controlled study

Participants

Participants with CKD and elevated serum parathyroid hormone levels

Interventions

AMG‐073

Outcomes

Unclear

Notes

Reported as published by the University of Pennsylvania at http://renal2.med.upenn.edu/ but URL link broken and unable to obtain information about study to ascertain details and eligibility for this review

Ca x P ‐ calcium phosphorous product; CKD ‐ chronic kidney diease; iPTH ‐ intact parathyroid hormone; RCT ‐ randomised controlled trial

Data and analyses

Open in table viewer
Comparison 1. Calcimimetics 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

16

7351

Risk Ratio (IV, Random, 95% CI)

0.96 [0.89, 1.05]

Analysis 1.1

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 1 All‐cause mortality.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 1 All‐cause mortality.

1.1 GFR category G5 treated with dialysis

14

6893

Risk Ratio (IV, Random, 95% CI)

0.97 [0.89, 1.05]

1.2 GFR category G3a to G4

2

458

Risk Ratio (IV, Random, 95% CI)

0.29 [0.06, 1.48]

2 Cardiovascular mortality Show forest plot

9

5000

Risk Ratio (IV, Random, 95% CI)

0.68 [0.32, 1.45]

Analysis 1.2

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 2 Cardiovascular mortality.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 2 Cardiovascular mortality.

2.1 GFR category G5 treated with dialysis

7

4542

Risk Ratio (IV, Random, 95% CI)

0.67 [0.16, 2.87]

2.2 GFR category G3a to G4

2

458

Risk Ratio (IV, Random, 95% CI)

0.29 [0.06, 1.48]

3 Parathyroidectomy Show forest plot

5

4893

Risk Ratio (IV, Random, 95% CI)

0.49 [0.40, 0.59]

Analysis 1.3

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 3 Parathyroidectomy.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 3 Parathyroidectomy.

4 Fractures Show forest plot

2

3965

Risk Ratio (IV, Random, 95% CI)

0.52 [0.12, 2.27]

Analysis 1.4

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 4 Fractures.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 4 Fractures.

5 Hypocalcaemia Show forest plot

14

6864

Risk Ratio (IV, Random, 95% CI)

7.38 [5.43, 10.03]

Analysis 1.5

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 5 Hypocalcaemia.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 5 Hypocalcaemia.

5.1 GFR category G5 treated with dialysis

12

6415

Risk Ratio (IV, Random, 95% CI)

6.98 [5.10, 9.53]

5.2 GFR category G3a to G4

2

449

Risk Ratio (IV, Random, 95% CI)

31.90 [5.28, 192.60]

6 Hypercalcaemia Show forest plot

4

4662

Risk Ratio (IV, Random, 95% CI)

0.23 [0.05, 0.97]

Analysis 1.6

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 6 Hypercalcaemia.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 6 Hypercalcaemia.

7 Nausea Show forest plot

14

6899

Risk Ratio (IV, Random, 95% CI)

2.05 [1.54, 2.75]

Analysis 1.7

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 7 Nausea.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 7 Nausea.

7.1 GFR category G5 treated with dialysis

12

6450

Risk Ratio (IV, Random, 95% CI)

2.02 [1.45, 2.81]

7.2 GFR category G3a to G4

2

449

Risk Ratio (IV, Random, 95% CI)

2.26 [1.29, 3.95]

8 Vomiting Show forest plot

10

6718

Risk Ratio (IV, Random, 95% CI)

1.95 [1.74, 2.18]

Analysis 1.8

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 8 Vomiting.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 8 Vomiting.

8.1 GFR category G5 treated with dialysis

9

6323

Risk Ratio (IV, Random, 95% CI)

1.97 [1.73, 2.24]

8.2 GFR category G3a to G4

1

395

Risk Ratio (IV, Random, 95% CI)

1.77 [0.90, 3.48]

9 Diarrhoea Show forest plot

8

5639

Risk Ratio (IV, Random, 95% CI)

1.15 [1.02, 1.29]

Analysis 1.9

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 9 Diarrhoea.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 9 Diarrhoea.

10 Abdominal pain Show forest plot

4

831

Risk Ratio (IV, Random, 95% CI)

1.62 [0.55, 4.82]

Analysis 1.10

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 10 Abdominal pain.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 10 Abdominal pain.

11 Upper respiratory tract infection Show forest plot

4

1856

Risk Ratio (IV, Random, 95% CI)

0.95 [0.39, 2.33]

Analysis 1.11

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 11 Upper respiratory tract infection.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 11 Upper respiratory tract infection.

12 Asthenia, muscle weakness or paraesthesia Show forest plot

5

1379

Risk Ratio (IV, Random, 95% CI)

1.55 [0.93, 2.58]

Analysis 1.12

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 12 Asthenia, muscle weakness or paraesthesia.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 12 Asthenia, muscle weakness or paraesthesia.

12.1 Asthenia

2

790

Risk Ratio (IV, Random, 95% CI)

1.54 [0.26, 8.98]

12.2 Muscle weakness or paraesthesia

4

589

Risk Ratio (IV, Random, 95% CI)

1.78 [1.00, 3.14]

13 Dyspnoea Show forest plot

2

250

Risk Ratio (IV, Random, 95% CI)

1.02 [0.49, 2.12]

Analysis 1.13

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 13 Dyspnoea.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 13 Dyspnoea.

14 Headache Show forest plot

3

1115

Risk Ratio (IV, Random, 95% CI)

1.11 [0.65, 1.91]

Analysis 1.14

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 14 Headache.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 14 Headache.

15 Achievement of PTH target Show forest plot

11

2853

Risk Ratio (IV, Random, 95% CI)

3.06 [1.89, 4.98]

Analysis 1.15

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 15 Achievement of PTH target.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 15 Achievement of PTH target.

16 PTH Show forest plot

7

1935

Mean Difference (IV, Random, 95% CI)

‐280.39 [‐325.84, ‐234.94]

Analysis 1.16

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 16 PTH.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 16 PTH.

17 Serum calcium Show forest plot

7

1556

Mean Difference (IV, Random, 95% CI)

‐0.87 [‐0.96, ‐0.77]

Analysis 1.17

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 17 Serum calcium.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 17 Serum calcium.

18 Serum phosphorous Show forest plot

8

2300

Mean Difference (IV, Random, 95% CI)

‐0.23 [‐0.58, 0.12]

Analysis 1.18

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 18 Serum phosphorous.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 18 Serum phosphorous.

19 Calcium x phosphorous Show forest plot

8

2395

Mean Difference (IV, Random, 95% CI)

‐5.25 [‐9.16, ‐1.34]

Analysis 1.19

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 19 Calcium x phosphorous.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 19 Calcium x phosphorous.

Study flow diagram.
Figures and Tables -
Figure 1

Study flow diagram.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
Figures and Tables -
Figure 2

Risk of bias summary: review authors' judgements about each risk of bias item for each included study.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
Figures and Tables -
Figure 3

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 1 All‐cause mortality.
Figures and Tables -
Analysis 1.1

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 1 All‐cause mortality.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 2 Cardiovascular mortality.
Figures and Tables -
Analysis 1.2

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 2 Cardiovascular mortality.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 3 Parathyroidectomy.
Figures and Tables -
Analysis 1.3

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 3 Parathyroidectomy.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 4 Fractures.
Figures and Tables -
Analysis 1.4

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 4 Fractures.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 5 Hypocalcaemia.
Figures and Tables -
Analysis 1.5

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 5 Hypocalcaemia.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 6 Hypercalcaemia.
Figures and Tables -
Analysis 1.6

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 6 Hypercalcaemia.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 7 Nausea.
Figures and Tables -
Analysis 1.7

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 7 Nausea.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 8 Vomiting.
Figures and Tables -
Analysis 1.8

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 8 Vomiting.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 9 Diarrhoea.
Figures and Tables -
Analysis 1.9

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 9 Diarrhoea.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 10 Abdominal pain.
Figures and Tables -
Analysis 1.10

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 10 Abdominal pain.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 11 Upper respiratory tract infection.
Figures and Tables -
Analysis 1.11

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 11 Upper respiratory tract infection.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 12 Asthenia, muscle weakness or paraesthesia.
Figures and Tables -
Analysis 1.12

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 12 Asthenia, muscle weakness or paraesthesia.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 13 Dyspnoea.
Figures and Tables -
Analysis 1.13

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 13 Dyspnoea.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 14 Headache.
Figures and Tables -
Analysis 1.14

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 14 Headache.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 15 Achievement of PTH target.
Figures and Tables -
Analysis 1.15

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 15 Achievement of PTH target.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 16 PTH.
Figures and Tables -
Analysis 1.16

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 16 PTH.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 17 Serum calcium.
Figures and Tables -
Analysis 1.17

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 17 Serum calcium.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 18 Serum phosphorous.
Figures and Tables -
Analysis 1.18

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 18 Serum phosphorous.

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 19 Calcium x phosphorous.
Figures and Tables -
Analysis 1.19

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 19 Calcium x phosphorous.

Summary of findings for the main comparison. Summary of findings for dialysis patients

Cinacalcet plus standard therapy versus placebo or standard therapy or both for patients with CKD and elevated PTH levels

Patient or population: adults with CKD

Outcomes

(median treatment duration)

*Best estimate of control group risk

Relative effect
(95% CI)

No of participants
(studies)

Absolute effect per one year of treatment for 1000 treated (95%CI)

Quality of the evidence
(GRADE)

GFR category G5 treated with dialysis

All‐cause mortality

(8 months)

200 per 1000

RR 0.97 (0.89 to 95)

6893 (14)

6 fewer (22 fewer to 10 more)

⊕⊕⊕⊕
high

Parathyroidectomy

(9 months)

7 per 1000

RR 0.49 (0.40 to 0.59)

4893 (5)

3 fewer (4 fewer to 3 fewer)

⊕⊕⊕⊕
high

Hypocalcaemia

(7 months)

10 per 1000

RR 6.98 (5.10 to 9.53)

6415 (12)

60 more (41 more to 85 more)

⊕⊕⊕⊕
high

Nausea

(7 months)

150 per 1000

RR 2.02 (1.45 to 2.81)

6450 (12)

153 more (68 more to 272 more)

⊕⊕⊕
moderate

GFR category G3a‐G4

All‐cause mortality

(8 months)

25 per 1000

RR 0.29 (0.06 to 1.48)

458 (2)

18 fewer (23 fewer to 12 more)

⊕⊕
low

Parathyroidectomy

(9 months)

7 per 1000

RR not estimable

0 (0)

Not estimable

nil

Hypocalcaemia

(7 months)

10 per 1000

RR 31.9 (5.28 to 192.6)

449 (2)

310 more (43 more to 1910 more)


very low

Nausea

(7 months)

100 per 1000

RR 2.26 (1.29 to 3.95)

449 (2)

126 more (29 more to 295 more)

⊕⊕

low

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval; RR: Risk Ratio;

Approximate absolute event rates of outcomes per year are derived from previously published cohort studies and registry data for the outcomes of all‐cause mortality (Weiner 2006) and parathyroidectomy (Kestenbaum 2004) or event rates in the control arm of contributing studies for outcomes of hypocalcaemia and nausea. Absolute numbers of people who had chronic kidney disease with mortality or parathyroidectomy events avoided or nausea or hypocalcaemia events caused per 1000 treated were calculated from the risk estimate for the outcome (and associated 95% confidence interval) obtained from meta‐analysis of placebo‐controlled studies together with the absolute population risk estimates.

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

CKD ‐ chronic kidney disease; GFR ‐ glomerular filtration rate; PTH‐ parathyroid hormone

Figures and Tables -
Summary of findings for the main comparison. Summary of findings for dialysis patients
Table 1. Current chronic kidney disease nomenclature used by KDIGO nomenclature

Prognosis of CKD by GFR and albuminuria categories: KDIGO 2012

Persistent albuminuria categories

Description and range

A1

Normal to

mildly

increased

A2

Moderately

increased

A3

Severely

increased

< 30 mg/g

< 3 mg/mmol

30 to 300 mg/g

3 to 30 mg/mmol

> 300 mg/g

> 30 mg/mmol

GFR categories

(mL/min per 1.73 m²)

Description and range

G1

G2

Normal or high

Mildly decreased

> 90

60 to 89

Low

Moderate

High

G3a

Mild to moderately decreased

45 to 59

Moderate

High

Very high

G3b

Moderate to severely decreased

30 to 44

High

Very high

G4

Severely decreased

15 to 29

Very high

G5

Kidney failure

< 15

Description of the Kidney Disease: Improving Global Outcomes (KDIGO) nomenclature for chronic kidney disease used in this review (see the full KDIGO CKD 2013 for additional information).

GFR ‐ glomerular filtration rate

Figures and Tables -
Table 1. Current chronic kidney disease nomenclature used by KDIGO nomenclature
Table 2. Definitions of parathyroid hormone target, and hypercalcaemia and hypocalcaemia endpoints

Study

Participants (treatment/control)

PTH level triggering reduction in cinacalcet dose

Calcium level triggering reduction in cinacalcet dose

Hypocalcaemia (study endpoint)

Hypercalcaemia (study endpoint)

ACHIEVE Study 2008

173 (87/86)

< 150 pg/mL

Symptoms of hypocalcaemia or < 7.5 mg/dL

< 8.4 mg/dL

> 10.2 mg/dL

ADVANCE Study 2010

360 (180/180)

‐‐

‐‐

Hypocalcaemia

Hypercalcaemia

Akiba 2008

121 (91/30)

‐‐

‐‐

Hypocalcaemia

‐‐

Block 2004a

741 (371/370)

< 100 pg/mL

Symptoms of hypocalcaemia or < 7.8 mg/dL

Withdrawal due to hypocalcaemia

‐‐

Charytan 2005

54 (27/27)

‐‐

Dose‐related adverse event or < 7.8 mg/dL

< 8.4 mg/dL

‐‐

Chonchol 2009

404 (302/102)

PTH < 35 pg/mL for stage 3 and < 70 pg/mL for stage 4

Symptoms of hypocalcaemia or < 7.5 mg/dL

< 7.5 mg/dL

‐‐

El Shafey 2011

82 (55/27)

< 92 pg/mL

Dose‐related adverse event or < 7.5 mg/dL

Hypocalcaemia

‐‐

EVOLVE study 2007

3883 (1948/1935)

< 150 pg/mL

< 7.5 mg/dL and/or symptoms of hypocalcaemia

< 8.0 mg/dL or < 7.5 mg/dL (unclear which threshold reported in study)

> 10.5 mg/dL

Fukagawa 2008

145 (72/73)

Investigators’ discretion or excessive decrease in PTH level

Investigators’ discretion or < 7.5 mg/dL

Hypocalcaemia

‐‐

Goodman 2000

21 (16/5)

‐‐

Symptoms of hypocalcaemia or ionised calcium < 4 mg/dL

Ionized calcium < 4 mg/dL

‐‐

Goodman 2002

30 (23/7)

‐‐

8.0 mg/dL

< 8.0 mg/dL

‐‐

Harris 2004

23 (17/6)

‐‐

‐‐

‐‐

‐‐

IMPACT SHPT Study 2012

264 (134/134)

< 150 pg/mL

< 7.5 mg/dL

<8,.4 mg/dL

> 10.5 mg/dL

Lindberg 2003

78 (39/39)

< 100 pg/mL

Symptoms of hypocalcaemia or < 7.8 mg/dL

< 7.5 mg/dL

‐‐

Lindberg 2005

395 (294/101)

‐‐

Symptoms of hypocalcaemia or < 7.8 mg/dL

‐‐

‐‐

Malluche 2008

32 (19/13)

< 100 pg/mL

Symptoms of hypocalcaemia or < 7.8 mg/dL

‐‐

‐‐

OPTIMA Study 2008

552 (368/184)

< 150 pg/mL

< 8.0 mg/dL

< 7.5 mg/dL

‐‐

Quarles 2003a

71 (36/35)

< 100 pg/mL

< 7.8 mg/dL

‐‐

‐‐

PTH ‐ parathyroid hormone

Figures and Tables -
Table 2. Definitions of parathyroid hormone target, and hypercalcaemia and hypocalcaemia endpoints
Comparison 1. Calcimimetics 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

16

7351

Risk Ratio (IV, Random, 95% CI)

0.96 [0.89, 1.05]

1.1 GFR category G5 treated with dialysis

14

6893

Risk Ratio (IV, Random, 95% CI)

0.97 [0.89, 1.05]

1.2 GFR category G3a to G4

2

458

Risk Ratio (IV, Random, 95% CI)

0.29 [0.06, 1.48]

2 Cardiovascular mortality Show forest plot

9

5000

Risk Ratio (IV, Random, 95% CI)

0.68 [0.32, 1.45]

2.1 GFR category G5 treated with dialysis

7

4542

Risk Ratio (IV, Random, 95% CI)

0.67 [0.16, 2.87]

2.2 GFR category G3a to G4

2

458

Risk Ratio (IV, Random, 95% CI)

0.29 [0.06, 1.48]

3 Parathyroidectomy Show forest plot

5

4893

Risk Ratio (IV, Random, 95% CI)

0.49 [0.40, 0.59]

4 Fractures Show forest plot

2

3965

Risk Ratio (IV, Random, 95% CI)

0.52 [0.12, 2.27]

5 Hypocalcaemia Show forest plot

14

6864

Risk Ratio (IV, Random, 95% CI)

7.38 [5.43, 10.03]

5.1 GFR category G5 treated with dialysis

12

6415

Risk Ratio (IV, Random, 95% CI)

6.98 [5.10, 9.53]

5.2 GFR category G3a to G4

2

449

Risk Ratio (IV, Random, 95% CI)

31.90 [5.28, 192.60]

6 Hypercalcaemia Show forest plot

4

4662

Risk Ratio (IV, Random, 95% CI)

0.23 [0.05, 0.97]

7 Nausea Show forest plot

14

6899

Risk Ratio (IV, Random, 95% CI)

2.05 [1.54, 2.75]

7.1 GFR category G5 treated with dialysis

12

6450

Risk Ratio (IV, Random, 95% CI)

2.02 [1.45, 2.81]

7.2 GFR category G3a to G4

2

449

Risk Ratio (IV, Random, 95% CI)

2.26 [1.29, 3.95]

8 Vomiting Show forest plot

10

6718

Risk Ratio (IV, Random, 95% CI)

1.95 [1.74, 2.18]

8.1 GFR category G5 treated with dialysis

9

6323

Risk Ratio (IV, Random, 95% CI)

1.97 [1.73, 2.24]

8.2 GFR category G3a to G4

1

395

Risk Ratio (IV, Random, 95% CI)

1.77 [0.90, 3.48]

9 Diarrhoea Show forest plot

8

5639

Risk Ratio (IV, Random, 95% CI)

1.15 [1.02, 1.29]

10 Abdominal pain Show forest plot

4

831

Risk Ratio (IV, Random, 95% CI)

1.62 [0.55, 4.82]

11 Upper respiratory tract infection Show forest plot

4

1856

Risk Ratio (IV, Random, 95% CI)

0.95 [0.39, 2.33]

12 Asthenia, muscle weakness or paraesthesia Show forest plot

5

1379

Risk Ratio (IV, Random, 95% CI)

1.55 [0.93, 2.58]

12.1 Asthenia

2

790

Risk Ratio (IV, Random, 95% CI)

1.54 [0.26, 8.98]

12.2 Muscle weakness or paraesthesia

4

589

Risk Ratio (IV, Random, 95% CI)

1.78 [1.00, 3.14]

13 Dyspnoea Show forest plot

2

250

Risk Ratio (IV, Random, 95% CI)

1.02 [0.49, 2.12]

14 Headache Show forest plot

3

1115

Risk Ratio (IV, Random, 95% CI)

1.11 [0.65, 1.91]

15 Achievement of PTH target Show forest plot

11

2853

Risk Ratio (IV, Random, 95% CI)

3.06 [1.89, 4.98]

16 PTH Show forest plot

7

1935

Mean Difference (IV, Random, 95% CI)

‐280.39 [‐325.84, ‐234.94]

17 Serum calcium Show forest plot

7

1556

Mean Difference (IV, Random, 95% CI)

‐0.87 [‐0.96, ‐0.77]

18 Serum phosphorous Show forest plot

8

2300

Mean Difference (IV, Random, 95% CI)

‐0.23 [‐0.58, 0.12]

19 Calcium x phosphorous Show forest plot

8

2395

Mean Difference (IV, Random, 95% CI)

‐5.25 [‐9.16, ‐1.34]

Figures and Tables -
Comparison 1. Calcimimetics versus placebo/no treatment