Work

Protein-bound Uremic Toxin Lowering Effects of Sevelamer in Hyperphosphatemic Hemodialysis Patients: A Multicenter Randomized Controlled Trial

Year: 2026

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

Abstract: Rationale & Objective P-cresyl sulfate (pCS) is an important protein-bound uremic toxin associated with high cardiovascular mortality in chronic hemodialysis (HD) patients. Data regarding pCS lowering and the pleiotropic effects of sevelamer in chronic HD patients are limited. Study Design Open-label, multicenter randomized controlled trial. Setting & Participants Chronic HD patients with hyperphosphatemia. Exposures Patients were randomly assigned to receive either sevelamer or calcium carbonate as phosphate binders for 24 weeks. Outcomes The primary outcome was the between-group difference in pCS change over 24 weeks. Secondary outcomes included changes in hs-CRP, iPTH, cardio-ankle vascular index, and adverse event rates. Analytical Approach Mean differences between groups were analyzed using a linear mixed model. Multivariate logistic regression was used to determine factors associated with decreased pCS levels. Results A total of 128 patients were enrolled, 4 dropped out, and 124 were analyzed. Residual kidney function (RKF) ≥100 mL/day was present in 47.7%. Both groups achieved significant phosphate reduction. Mean changes in pCS did not differ significantly between groups: 0.70 mg/L (95% CI, -1.04 to 2.44) in the sevelamer group versus -0.09 mg/L (95% CI, -1.70 to 1.51) in the calcium carbonate group (P=0.07). However, sevelamer was associated with a smaller increase in cardio-ankle vascular index than calcium carbonate (adjusted mean change difference, -0.63 [95% CI, -1.22 to -0.04]; P=0.04). Preserved RKF and high-dose phosphate binders were independently associated with decreased pCS levels. Limitations Change in pCS is only a surrogate marker for cardiovascular events, and the study may have been underpowered, or the sevelamer dose and treatment duration may have been insufficient. Conclusions PCS levels were not significantly changed in both groups. However, the increase in cardio-ankle vascular index was smaller with sevelamer than with calcium carbonate, independent of pCS change. Further trials with larger samples and longer treatment durations are warranted.

Source: Kidney Medicine

DOI: 10.1016/j.xkme.2026.101527