title: Sevelamer Versus Calcium-Based Binders for Treatment of Hyperphosphatemia in CKD: A Meta-Analysis of Randomized Controlled Trials.
abstract: OBJECTIVE
  People with CKD stages 3-5 and on dialysis (5D) have dramatically increased mortality, which has been associated with hyperphosphatemia in many studies. Oral phosphate binders are commonly prescribed to lower serum phosphate. We conducted an updated meta-analysis of the noncalcium-based binder (non-CBB) sevelamer versus CBBs in CKD stages 3-5D.
  
  
  METHODS
  Randomized, controlled trials comparing sevelamer with CBBs were identified through MEDLINE and the Cochrane Central Register of Controlled Trials. Patient-level outcomes included all-cause mortality, cardiovascular events and mortality, hospitalization, and adverse effects. Intermediate outcomes included vascular calcification and bone changes. Biochemical outcomes included serum phosphate, calcium, parathyroid hormone, lipids, and hypercalcemia. We conducted and reported this review according to Cochrane guidelines.
  
  
  RESULTS
  We included 25 studies to March 31, 2015 with 4770 participants (88% on hemodialysis). Patients receiving sevelamer had lower all-cause mortality (risk ratio [RR], 0.54; 95% confidence interval [95% CI], 0.32 to 0.93), no statistically significant difference in cardiovascular mortality (n=2712; RR, 0.33; 95% CI, 0.07 to 1.64), and an increase in combined gastrointestinal events of borderline statistical significance (n=384; RR, 1.42; 95% CI, 0.97 to 2.08). For biochemical outcomes, patients receiving sevelamer had lower total serum cholesterol (mean difference [MD], -20.2 mg/dl; 95% CI, -25.9 to -14.5 mg/dl), LDL-cholesterol (MD, -21.6 mg/dl; 95% CI, -27.9 to -15.4 mg/dl), and calcium (MD, -0.4 mg/dl; 95% CI, -0.6 to -0.2 mg/dl) and a reduced risk of hypercalcemia (RR, 0.30; 95% CI, 0.19 to 0.48). End of treatment intact parathyroid hormone was significantly higher for sevelamer (MD, 32.9 pg/ml; 95% CI, 0.1 to 65.7 pg/ml). Serum phosphate values showed no significant differences.
  
  
  CONCLUSIONS
  Patients with CKD stages 3-5D using sevelamer have lower all-cause mortality compared with those using CBBs. Because of a lack of placebo-controlled studies, questions remain regarding phosphate binder benefits for patients with CKD stages 3-5 and not on dialysis.
authors.affiliation: Cornerstone Research Group, Burlington, Ontario, Canada;
authors.forename: Leena
authors.initials: L
authors.lastname: Patel
authors.affiliation: Cornerstone Research Group, Burlington, Ontario, Canada;
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Bernard
authors.affiliation: Department of Renal Medicine, Westmead Hospital, Westmead, New South Wales, Australia; and Osteoporosis and Bone Biology Division, Garvan Institute of Medical Research, Sydney, Australia g.elder@garvan.org.au.
authors.forename: Grahame J
authors.initials: GJ
authors.lastname: Elder
mesh_terms: D015415:Biomarkers / Q000097:blood; D017610:Calcium Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D002614:Chelating Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016009:Chi-Square Distribution; D006801:Humans; D054559:Hyperphosphatemia / Q000097:blood / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D016017:Odds Ratio; D010710:Phosphates / Q000097:blood*; D016032:Randomized Controlled Trials as Topic; D006435:Renal Dialysis / Q000009:adverse effects / Q000401:mortality; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D012307:Risk Factors; D000069603:Sevelamer / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D017610:Calcium Compounds; D002614:Chelating Agents; D010710:Phosphates; D000069603:Sevelamer
keywords: calcium; chronic kidney disease; hospitalization; humans; meta-analysis; mortality; phosphate binders; randomized controlled trials as topic; sevelamer