Protein-bound Uremic Toxin Lowering Effects of Sevelamer in Hyperphosphatemic Hemodialysis Patients: A Multicenter Randomized Controlled Trial
In brief
Sevelamer reduced the vascular stiffness index rise by 0.63 points, not toxin levels
In this 24-week trial of 124 hemodialysis patients, sevelamer did not significantly lower p-cresyl sulfate compared with calcium carbonate. It was linked to a 0.63-point smaller increase in the cardio-ankle vascular index, a measure of arterial stiffness, but the study did not assess cardiovascular events; larger, longer trials are needed to clarify the clinical importance.
- Journal
- Kidney medicine (Q1)
- Published
- 11 September 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Napas Srifa, Jeerath Phannajit, Patchara Tanateerapong, Kamonrat Chongthanakorn, Sipanan Thamratnopkoon, Wannasit Wathanavasin, et al.
- PMID
- 42959526
- DOI
- 10.1016/j.xkme.2026.101527
Why clinicians should know about it
- Picked for Nephrology (top studies of the week, 1 November 2026): Sevelamer vs calcium carbonate in long‑term HD patients
Abstract
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.