Sevelamer remt vaatstijfheid sterker dan calciumcarbonaat bij dialysepatiënten — multicenter RCT

RATIONALE & OBJECTIVE: 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. STUDY DESIGN: Open-label, multicenter randomized controlled trial. SETTING & PARTICIPANTS: Patients with hyperphosphatemia receiving long-term HD. 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 high-sensitivity C-reactive protein levels, intact parathyroid hormone levels, 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. 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.