Plasma p-cresol lowering effect of sevelamer in non-dialysis CKD patients: evidence from a randomized controlled trial

Riccio, Eleonora; Sabbatini, Massimo; Bruzzese, Dario; Grumetto, Lucia; Marchetiello, Cristina; Amicone, Maria; Andreucci, Michele; Guida, Bruna; Passaretti, Davide; Russo, Giacomo; Pisani, Antonio

Abstract

Background
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.

Methods
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.

Results
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.

Conclusions
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.

• Journal Article Type: Article
• Acceptance Date: Oct 31, 2017
• Online Publication Date: Nov 20, 2017
• Publication Date: 2018-06
• Deposit Date: May 4, 2020
• Journal: Clinical and Experimental Nephrology
• Print ISSN: 1342-1751
• Electronic ISSN: 1437-7799
• Publisher: BMC
• Peer Reviewed: Peer Reviewed
• Volume: 22
• Issue: 3
• Pages: 529-538
• DOI: https://doi.org/10.1007/s10157-017-1504-8
• Keywords: Chronic kidney disease, p-Cresol, Sevelamer, Cardiovascular risk
• Public URL: http://researchrepository.napier.ac.uk/Output/2658200