Calcimimetics for secondary hyperparathyroidism in chronic kidney disease patients

Giovanni FM Strippoli; Allison Tong; Suetonia C Palmer; Grahame J Elder; Jonathan C Craig

doi:10.1002/14651858.CD006254

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Figure 1

Flow chart of study identification

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Analysis 1.1

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

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Analysis 1.2

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 2 30% or more decrease in mean PTH level.

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Analysis 1.4

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

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Analysis 1.5

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

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Analysis 1.6

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

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Analysis 1.7

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

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Analysis 1.8

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 8 Asthenia, muscle weakness or paraesthesia.

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Analysis 1.9

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

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Analysis 1.10

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 10 Upper respiratory tract infection.

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Analysis 1.11

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 11 Parathyroidectomy.

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Analysis 1.12

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 12 Headache.

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Analysis 1.13

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

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Analysis 1.14

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

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Analysis 1.15

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 15 Mixed uraemic osteodystrophy.

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Analysis 1.17

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 17 PTH (pg/mL).

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Analysis 1.18

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 18 Calcium (mg/dL).

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Analysis 1.19

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 19 Phosphorus (mg/dL).

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Analysis 1.20

Comparison 1 Calcimimetics versus placebo/no treatment, Outcome 20 Calcium x phosphorus.

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Table 1. Electronic search strategies

Database	Search terms
CENTRAL	1. KIDNEY DISEASES single term 2. KIDNEY FAILURE single term 3. KIDNEY FAILURE CHRONIC single term 4. RENAL DIALYSIS explode all trees 5. (hemodialysis or haemodialysis) 6. dialysis 7. (capd or ccpd or apd) 8. predialysis 9. ((chronic next renal) or (chronic next kidney)) 10. (kidney next disease) 11. (kidney next failure) 12. (#1 or #2 or #3 or #4 or #5 or #6 or #7 or #8 or #9 or #10 or #11) 13. BONE DISEASES explode all trees 14. RENAL OSTEODYSTROPHY single term 15. (bone next disease) 16. (bone* and (atroph* or formation or deform* or destruct* or necrosis or resorption or metabol* or turnover or demineral* or decalcif* or density)) 17. (osteo* or hyperparathyroid) 18. (#13 or #14 or #15 or #16 or #17) 19. (#12 and #18) 20. calcimimetic 21. cinacalcet 22. NAPHTHALENES single term 23. (#20 or #21 or #22) 24. (#19 and #23)
MEDLINE	1. Kidney Diseases/ 2. Kidney Failure/ 3. Kidney Failure Chronic/ 4. exp Renal Dialysis/ 5. ((kidney$ or renal) and (dialysis or failure)).tw. 6. (hemodialysis or haemodialysis).tw. 7. (peritoneal dialysis or CAPD or CCPD or APD).tw. 8. or/1‐7 9. exp Bone Diseases/ 10. bone disease$.tw. 11. (bone$ and (atroph$ or formation or deform$ or destruct$ or necrosis or resorption or metabol$ or turnover or demineral$ or decalcif$ or density)).tw. 12. (osteo$ or hyperparathyroid$).tw. 13. or/9‐12 14. 8 and 13 15. Renal Osteodystrophy/ 16. 14 or 15 17. randomized controlled trial.pt. 18. controlled clinical trial.pt. 19. randomized controlled trials/ 20. random allocation/ 21. double blind method/ 22. single blind method/ 23. or/17‐22 24. animals/ not (animals/ and human/) 25. 23 not 24 26. clinical trial.pt. 27. exp clinical trials/ 28. (clinic$ adj25 trial$).ti,ab. 29. cross‐over studies/ 30. (crossover or cross‐over or cross over).tw. 31. ((singl$ or doubl$ or trebl$ or tripl$) adj25 (blind$ or mask$)).ti,ab. 32. placebos/ 33. placebo$.ti,ab. 34. random$.ti,ab. 35. research design/ 36. or/26‐35 37. 36 not 24 38. 25 or 37 39. 16 and 38
EMBASE	1. Kidney Disease/ 2. Kidney Failure/ 3. Chronic Kidney Failure/ 4. exp hemodialysis/ 5. (hemodialysis or haemodialysis).tw. 6. dialysis.tw. 7. (CAPD or CCPD or APD).tw. 8. predialysis.tw. 9. (chronic renal or chronic kidney).tw. 10. or/1‐9 11. exp Bone Disease/ 12. bone disease$.tw. 13. (bone$ and (atroph$ or formation or deform$ or destruct$ or necrosis or resorption or metabol$ or turnover or demineral$ or decalcif$ or density)).tw. 14. (osteo$ or hyperparathyroid$).tw. 15. Renal Osteodystrophy/ 16. or/11‐15 17. 10 and 16 18. Calcimimetic Agent/ 19. Cinacalcet/ 20. naphthalene derivative/ or naphthalene/ 21. ("R‐568" or "AMG 074" or "AMG 073" or "KRN 1493").tw. 22. calcimimetic$.tw. 23. cinacalcet.tw. 24. or/18‐23 25. and/17,24

Table 1. Electronic search strategies

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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	5	1285	Risk Ratio (M‐H, Random, 95% CI)	0.75 [0.30, 1.88]

2 30% or more decrease in mean PTH level Show forest plot	4	1284	Risk Ratio (M‐H, Random, 95% CI)	4.49 [3.04, 6.64]

3 Fractures	0	0	Risk Difference (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
4 Hypocalcaemia Show forest plot	4	868	Risk Ratio (M‐H, Random, 95% CI)	2.89 [0.71, 11.73]

5 Nausea Show forest plot	5	1263	Risk Ratio (M‐H, Random, 95% CI)	1.40 [1.00, 1.95]

6 Vomiting Show forest plot	2	1136	Risk Ratio (M‐H, Random, 95% CI)	1.89 [1.47, 2.43]

7 Dyspnoea Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

8 Asthenia, muscle weakness or paraesthesia Show forest plot	2		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

8.1 Asthenia	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
8.2 Muscle weakness or paraesthesia	1		Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
9 Hypotension Show forest plot	2	1136	Risk Ratio (M‐H, Random, 95% CI)	0.53 [0.36, 0.79]

10 Upper respiratory tract infection Show forest plot	2	1136	Risk Ratio (M‐H, Random, 95% CI)	0.86 [0.34, 2.18]

11 Parathyroidectomy Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

12 Headache Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

13 Abdominal pain Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

14 Diarrhoea Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

15 Mixed uraemic osteodystrophy Show forest plot	1		Risk Ratio (M‐H, Random, 95% CI)	Totals not selected

16 Bone histomorphometry	0	0	Risk Ratio (M‐H, Random, 95% CI)	0.0 [0.0, 0.0]
17 PTH (pg/mL) Show forest plot	4	1276	Mean Difference (IV, Random, 95% CI)	‐290.79 [‐360.23, ‐221.34]

18 Calcium (mg/dL) Show forest plot	3	1201	Mean Difference (IV, Random, 95% CI)	‐0.77 [‐0.93, ‐0.60]

19 Phosphorus (mg/dL) Show forest plot	3	1195	Mean Difference (IV, Random, 95% CI)	‐0.29 [‐0.50, ‐0.08]

20 Calcium x phosphorus Show forest plot	3	1194	Mean Difference (IV, Random, 95% CI)	‐7.90 [‐10.25, ‐5.54]

Comparison 1. Calcimimetics versus placebo/no treatment

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