Sevelamer Versus Calcium-Based Binders for Treatment of Hyperphosphatemia in CKD: A Meta-Analysis of Randomized Controlled Trials

Abstract

Background and objectives: 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.

Design, setting, participants, & measurements: 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.

Keywords: calcium; chronic kidney disease; hospitalization; humans; meta-analysis; mortality; phosphate binders; randomized controlled trials as topic; sevelamer.

Figure 1.

Flow diagram of the literature search. Electronic searches from March of 2009 to March of 2015 identified 1807 potentially relevant reports. Of these, 1770 were excluded after title and abstract review. Full text was reviewed on 37 reports; ten publications (36–45) reporting eight new studies (n=1213) were eligible. Combining these eight with the 2011 Cochrane study set by Navaneethan et al. (8) yielded a final set of 25 studies (n=4770). RCT, randomized, controlled trial.

Figure 2.

Effect of sevelamer versus calcium-based binders on all-cause mortality in patients with CKD. Compared with calcium-based binders (CBBs), sevelamer significantly lowered all-cause mortality in patients with CKD stages 3–5 and on dialysis. 95% CI, 95% confidence interval; BRiC, phosphate binder Impact on Bone Remodeling and Coronary Calcification; CARE, Calcium Acetate Renagel Evaluation; CARE-2, Calcium Acetate Renagel Evaluation-2; DCOR, Dialysis Clinical Outcomes Revisited; df, degree of freedom; INDEPENDENT-HD, Reduce Cardiovascular Calcifications to Reduce QT Interval in Dialysis; M-H, Mantel–Haenszel.