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

p-Cresyl sulfate (pCS) is an important protein-bound uremic toxin associated with high cardiovascular mortality in patients receiving long-term hemodialysis (HD). Data regarding pCS lowering and the pleiotropic effects of sevelamer are limited in patients receiving long-term HD.

Open-label, multicenter randomized controlled trial.

Patients with hyperphosphatemia receiving long-term HD.

Patients were randomly assigned to receive either sevelamer or calcium carbonate as phosphate binders for 24 weeks.

The primary outcome was the between-group difference in pCS change over 24 weeks. Secondary outcomes included changes in high-sensitivity C-reactive protein levels, intact parathyroid hormone levels, cardio-ankle vascular index, and adverse event rates.

Mean differences between groups were analyzed using a linear mixed model. Multivariate logistic regression was used to determine factors associated with decreased pCS levels.

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.

Change in pCS is only a surrogate marker for cardiovascular events. The study may have been underpowered, or the sevelamer dose and treatment duration may have been insufficient.

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.