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

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.

• Authors: Eleonora Riccio, Massimo Sabbatini, Dario Bruzzese, Lucia Grumetto, Cristina Marchetiello, Maria Amicone, Michele Andreucci, Bruna Guida, Davide Passaretti, Giacomo Russo, Antonio Pisani
• Journal: Clinical and experimental nephrology (Clin Exp Nephrol) Vol. 22 Issue 3 Pg. 529-538 (Jun 2018) ISSN: 1437-7799 [Electronic] Japan
• PMID: 29159529 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Chelating Agents
• Cresols
• 4-cresol
• Sevelamer

Topics

• Adult
• Aged
• Chelating Agents (pharmacology, therapeutic use)
• Cresols (blood)
• Female
• Humans
• Male
• Middle Aged
• Renal Insufficiency, Chronic (blood, drug therapy)
• Sevelamer (pharmacology, therapeutic use)