Plasma p-cresol lowering effect of sevelamer in non-dialysis CKD patients: evidence from a randomized controlled trial
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The accumulation of p-cresol, a metabolic product of aromatic amino acids generated by intestinal microbiome, increases the cardiovascular risk in chronic kidney disease (CKD) patients. Therefore, therapeutic strategies to reduce plasma p-cresol levels are highly demanded. It has been reported that the phosphate binder sevelamer (SEV) sequesters p-cresol in vitro, while in vivo studies on dialysis patients showed controversial results. Aim of our study was to evaluate the effect of SEV on p-cresol levels in non-dialysis CKD patients.
This was a single-blind, randomized placebo-controlled trial (Registration number NCT02199444) carried on 69 CKD patients (stage 3–5, not on dialysis), randomly assigned (1:1) to receive either SEV or placebo for 3 months. Total p-cresol serum levels were evaluated at baseline (T0), and 1 (T1) and 3 months (T3) after treatment start. The primary end-point was to evaluate the effect of SEV on p-cresol levels.
Compared to baseline (T0, 7.4 ± 2.7 mg/mL), p-cresol mean concentration was significantly reduced in SEV patients after one (− 2.06 mg/mL, 95% CI − 2.62 to − 1.50 mg/mL; p < 0.001) and 3 months of treatment (− 3.97 mg/mL, 95% CI − 4.53 to − 3.41 mg/mL; p < 0.001); no change of plasma p-cresol concentration was recorded in placebo-treated patients. Moreover, P and LDL values were reduced after 3 months of treatment by SEV but not placebo.
In conclusion, our study represents the first evidence that SEV is effective in reducing p-cresol levels in CKD patients in conservative treatment, and confirms its beneficial effects on inflammation and lipid pattern.
KeywordsChronic kidney disease p-Cresol Sevelamer Cardiovascular risk
Compliance with ethical standards
Conflict of interest
All the authors have declared that no conflict of interest exists.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee at which the studies were conducted (IRB approval number 15/12) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Human and animal rights statement
This article does not contain any studies with animals performed by any of the authors.
Informed consent was obtained from all individual participants included in the study.
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