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

@article{srifa2026proteinbound,
  title = {{Protein-bound Uremic Toxin Lowering Effects of Sevelamer in Hyperphosphatemic Hemodialysis Patients: A Multicenter Randomized Controlled Trial}},
  author = {Napas Srifa and Jeerath Phannajit and Patchara Tanateerapong and Kamonrat Chongthanakorn and Sipanan Thamratnopkoon and Wannasit Wathanavasin and Supat Vanichakarn and Sookruethai Lekhyananda and Yingyos Avihingsanon and Kearkiat Praditpornsilpa and Somchai Eiam-Ong and Paweena Susantitaphong},
  journal = {Kidney Medicine},
  year = {2026},
  month = sep,
  doi = {10.1016/j.xkme.2026.101527},
  url = {https://doi.org/10.1016/j.xkme.2026.101527},
  note = {CC BY},
}

TY  - JOUR
TI  - Protein-bound Uremic Toxin Lowering Effects of Sevelamer in Hyperphosphatemic Hemodialysis Patients: A Multicenter Randomized Controlled Trial
AU  - Napas Srifa
AU  - Jeerath Phannajit
AU  - Patchara Tanateerapong
AU  - Kamonrat Chongthanakorn
AU  - Sipanan Thamratnopkoon
AU  - Wannasit Wathanavasin
AU  - Supat Vanichakarn
AU  - Sookruethai Lekhyananda
AU  - Yingyos Avihingsanon
AU  - Kearkiat Praditpornsilpa
AU  - Somchai Eiam-Ong
AU  - Paweena Susantitaphong
PY  - 2026
DA  - 2026/09/11
JO  - Kidney Medicine
DO  - 10.1016/j.xkme.2026.101527
UR  - https://doi.org/10.1016/j.xkme.2026.101527
AB  - 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. Plain-Language Summary: People on long-term hemodialysis can build up harmful waste products in the blood, including p-cresyl sulfate, which has been linked to heart and blood vessel problems. We studied whether sevelamer, a common phosphate binder, could lower this toxin and provide added benefits compared with calcium carbonate. In this multicenter randomized trial, adults receiving long-term hemodialysis with high phosphate levels received one of these treatments for 24 weeks. Both treatments lowered phosphate levels, but neither clearly lowered p-cresyl sulfate levels more than the other. However, sevelamer was linked to less worsening in a measure of arterial stiffness. Preserved residual kidney function and higher phosphate binder doses were also linked to lower toxin levels. These findings may help inform future dialysis care and research.
SN  - 2590-0595
ER  -