Chulalongkorn University Theses and Dissertations (Chula ETD)

Protein-bound Uremic Toxins Lowering Effect of Sevelamer in Pre-dialysis Chronic Kidney Disease Patients with Hyperphosphatemia: A Randomized Controlled Trial

Kullaya Takkavatakarn, Faculty of Medicine


Background: P-cresyl sulfate and indoxyl sulfate are strongly associated with cardiovascular events, and all-cause mortality in chronic kidney disease (CKD). This study was conducted to compare the effects between sevelamer and calcium carbonate on protein-bound uremic toxins in pre-dialysis CKD patients with hyperphosphatemia. Methods: After 2 weeks of the run-in period, 40 pre-dialysis CKD patients with persistent hyperphosphatemia were randomly assigned to receive either daily 2,400 mg of sevelamer or 1,500 mg of calcium carbonate for 24 weeks. Serum p-cresyl sulfate, indoxyl sulfate, fibroblast growth factor 23 (FGF23), lipid profiles, and high sensitivity C-reactive protein (hs-CRP) were evaluated. The primary endpoint was to evaluate the effect of sevelamer on p-cresyl sulfate level. Results: After 24 weeks, a significant decrease of serum p-cresyl sulfate was observed in sevelamer compared with calcium carbonate therapy (mean difference -5.61 mg/L; 95% CI -11.01 to -0.27 mg/L; p=0.04). Sevelamer had obvious effects in lowering FGF23 (p= 0.007) and LDL-cholesterol levels (p<0.001) but did not affect serum indoxyl sulfate and hs-CRP levels. Conclusions: Sevelamer could effectively reduce serum p-cresyl sulfate, FGF23 levels, and improve lipid profiles in pre-dialysis CKD patients with hyperphosphatemia. Our data suggest the additional benefits of sevelamer over calcium-based phosphate binder in cardiovascular protection.