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1 Supplementary Materials Tables S1, S2, S3: Please refer to article content regarding search strategies (Tables S1 and S2) and data point corrections from the 2011 Cochrane meta-analysis (Table S3). Table S1: Electronic search strategy CENTRAL database search terms 1. KIDNEY DISEASES 2. KIDNEY FAILURE CHRONIC 3. KIDNEY FAILURE 4. REL REPLACEMENT THERAPY 5. REL DIALYSIS 6. HEMOFILTRATION 7. (chronic next kidney) or (chronic next renal) 8. (ckd or ckf or crd or eskd or esrd or eskf or esrf) 9. (predialysis or dialysis) 10. (haemodialysis or hemodialysis) 11. (capd or ccpd or apd) (Word variations have been searched) 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 14. REL OSTEODYSTROPHY 15. (bone next disease*) 16. (bone* and (atrophy* or formation or deform* or destruct* or necrosis or resorption or metabol* or turnover or demineral* or decalcif* or density)) (Word variations have been searched) 17. (#13 or #14 or #15 or #16) 18. (#12 and #17) 19. aluminum HYDROXIDE 20. CALCIUM CARBOTE 21. CALCIUM GLUCOTE 22. POLYAMINES 23. ANION EXCHANGE RESINS 24. ((phosphate next buffer*) or (phosphate next binder*)) 25. (aluminium next carbonate*) or (aluminum next carbonate*) 26. (calcium next acetate*) 27. (calcium next ketoglutarate*) 28. Sevelamer PubMed/MEDLINE database search terms 1. Kidney Diseases[mesh: noexp] 2. Kidney Failure, Chronic[mesh:noexp] 3. Kidney Failure[mesh:noexp] 4. Renal replacement therapy[mesh: noexp] OR renal dialysis[mesh] OR hemofiltration[mesh] 5. (chronic kidney[tw] OR chronic renal[tw]) 6. (CKD[tw] OR CKF[tw] OR CRF[tw] OR ESKD[tw] OR ESRD[tw] OR ESKF[tw] OR ESRF[tw] 7. (predialysis[tw] OR dialysis[tw]) 8. (haemodialysis[tw] OR hemodialysis[tw]) 9. (CAPD[tw] OR CCPD[tw] OR APD[tw]) 10. #1 OR #2 OR #3 OR #4 OR #5 OR #6 OR #7 OR #8 OR #9 11. Bone Diseases[mesh] 12. Renal Osteodystrophy[mesh:noexp] 13. Bone disease*[tw] 14. (bone*[tw] AND (atrophy* OR formation[tw] OR deform*[tw] OR destruct* OR necrosis[tw] OR resorption[tw] OR metabol*[tw] OR turnover[tw] OR demineral*[tw] OR decalcif*[tw] OR density[tw]) 15. (osteo*)[tw] OR hyperparathyroid*[tw] OR hyperphosphat*[tw]) 16. #11 OR #12 OR #13 OR #14 OR # #10 and # Aluminium Hydroxide[mesh:noexp] 19. Calcium Carbonate[mesh:noexp] 20. Calcium Gluconate[mesh:noexp] 21. Polyamines[mesh:noexp] 22. Anion Exchange Resins[mesh:noexp] 23. (phosphate buffer*[tw] OR
2 29. (lanthanum next carbonate*) 30. (magnesium next carbonate*) 31. ((aluminum next hydroxide*) or (aluminium next hydroxide*) 32. Colestimide 33. Phoslo 34. Renagel 35. Fosrenol:ti, ab, kw (Word variations have been searched) 36. #19 or #20 or #21 or #22 or #23 or #24 or #25 or #26 or #27 or #28 or #29 or #30 or #31 or #32 or #33 or #34 or # (#18 and #36) phosphate bind*[tw]) 24. (alumin*um carbonate*[tw] OR aluminum carbonate*[tw] OR aluminum carbonate*[tw] 25. Calcium acetate*[tw] 26. Calcium ketoglutarate*[tw] 27. Sevelamer[tw] 28. Lanthanum carbonate*[tw] 29. Magnesium carbonate*[tw] 30. (alumin*um hydroxide[tw] OR aluminum carbonate*[tw] OR aluminum hydroxide*[tw] 31. Colestimide[tw] 32. Phoslo[tw] 33. Renagel[tw] 34. Fosrenol[tw] 35. #18 OR #19 OR #20 OR #21 OR #22 OR #23 OR #24 OR #25 OR #26 OR #27 OR #28 OR #29 OR #30 OR #31 OR #32 OR #33 OR # #17 AND #35
3 Table S2: Journals and conferences searched by hand for sevelamer, phosphate binder, or phosphate binders from January 2009 to March 2015 Journals Advances in Renal Replacement Therapy American Journal of Kidney Diseases American Journal of Nephrology BMC Nephrology British Journal of Diabetes and Vascular Disease British Journal of Renal Medicine British Medical Journal Canadian Society of Nephrology Clinical and Experimental Nephrology Clinical Journal of the American Society of Nephrology Clinical Kidney Journal Clinical Nephrology Clinical Queries Nephrology Clinical Science Current Opinion in Nephrology and Hypertension Hong Kong Journal of Nephrology Indian Journal of Nephrology Indian Journal of Transplantation International Diabetes Federation World Diabetes Congress International Journal of Nephrology International Urology and Nephrology Iranian Journal of Kidney Diseases Journal of American Society of Nephrology Journal of Clinical Investigation Journal of Nephrology (Journal of the Italian Society of Nephrology) Journal of Nephrology and Renal Transplantation Journal of Nephrology and Renovascular Disease Journal of Nephrology and Therapeutics Journal of Renal Care Journal of Renal Nutrition Kidney Kidney International Kidney Research and Clinical Practice Kidney Research Journal Lancet Nephrology (Carlton) Congresses American College of Cardiology American Society of Hypertension (ASH) American Society of Nephrology (Kidney Week/Renal Week) ERA-EDTA Congress European Society of Hypertension National Kidney Foundation The Renal Association World Congress of Nephrology
4 Nephron New England Journal of Medicine Open Journal of Nephrology Renal Physiology Scandinavian Journal of Urology Seminars in Nephrology World Journal of Nephrology and Urology ERA-EDTA=European Renal Association-European Dialysis and Transplant Association.
5 Table S3: Summary of data points corrected from the 2011 Cochrane meta-analysis Study Outcome Correction Input reported in 2011 metaanalysis Chertow 2002 (31) Serum calcium Replaced baseline value for sevelamer (9 4 [SD 0 7]) with final value for sevelamer group (9 5 [SD 0 6]) DCOR Serum 2007 (37) calciumphosphorus product Serum total cholesterol Ferreira All-cause 2008 (36) mortality Russo Serum 2007 (25) phosphorus Serum calcium Sadek Serum 2003 (20) calciumphosphorus product Shaheen Serum alkaline 2004 (26) phosphatase Unit conversion of SD corrected from to Unit conversion of mean and SDs for both treatment groups corrected Moved from sevelamer versus calcium acetate subgroup to sevelamer versus calcium carbonate subgroup Moved from sevelamer versus calcium acetate subgroup to sevelamer versus calcium carbonate subgroup Moved from sevelamer versus calcium acetate subgroup to sevelamer versus calcium carbonate subgroup Data was reported in study but not in 2011 Cochrane Review; data was incorporated in the current review Data was reported in study but not in 2011 Cochrane Review; data was incorporated in the current review Baseline value for sevelamer group 9 4 (SD 0 7) Input reported in current meta-analysis Final value for sevelamer group 9 5 (SD 0 6) SD SD Calcium acetate: (SD 3 6) Sevelamer: (SD 34 8) Calcium acetate: (SD 34 8) Sevelamer: (SD 33 6)
6 Serum total cholesterol =not applicable. SD=standard deviation. Data was reported in study but not in 2011 Cochrane Review; data was incorporated in the current review
7 Figure S1. Risk of bias graph summarizing review authors judgments about each risk of bias item presented as percentages across all included studies. Incompleteness of outcome data was evaluated based on the percentage of participants excluded or lost to follow-up; studies with >20% exclusions or losses to follow-up were deemed incomplete.
8 Figures S2, S3, S4 Influence of outlier studies on the all-cause mortality meta-analysis was investigated visually via the forest plot (Figure 2), funnel plot (Figure S2), L Abbé plot (Figure S3), and influence analysis (Figure S4). Forest plotting showed that DCOR (37) and INDEPENDENT-HD (46) had large effect sizes with significant heterogeneity: the CIs of their effect estimates were disjoint. The L Abbé plot corroborated these two studies distinctiveness (Figure S3). Influence analysis showed the results were robust to the exclusion of single studies, excepting analyses omitting DCOR and INDEPENDENT-HD (Figure S4). Notably, heterogeneity significantly decreased when either DCOR (I 2 =38%) or INDEPENDENT-HD (I 2 =43%) was omitted.
9 Figure S2. Funnel plot of studies reporting all-cause mortality. RR = risk ratio; SE = standard error.
10 Figure S3. L Abbé plot examining outlier studies for effect of sevelamer and calcium-based binders on all-cause mortality. CBB = calcium-based phosphate binder. See References: Block 2005(29); BRiC Study 2008(14); CARE-2 Study 2008(35); Chertow 2002(31); DCOR Study 2007(37); Di Iorio 2012(44); Hervás 2003(28); INDEPENDENT Study 2013(46); Sadek 2003(20); CARE Study 2004(24); Ferreira 2008(36); Koiwa 2005(18)
11 Figure S4. Influential analysis describing the effect of removing a single study from the metaanalysis of all-cause mortality on the overall risk ratio. CI = confidence interval; RR = risk ratio
12 Figure S5. Effect of sevelamer versus calcium-based binders on serum phosphorus in patients with chronic kidney disease. M-H = Mantel-Haenszel test; CI = confidence interval
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