Eleonora Riccio1, Massimo Sabbatini2, Dario Bruzzese3, Lucia Grumetto4, Cristina Marchetiello2, Maria Amicone2, Michele Andreucci5, Bruna Guida6, Davide Passaretti7, Giacomo Russo4, Antonio Pisani2. 1. Department of Nephrology, Second University of Naples, Naples, Italy. elyriccio@libero.it. 2. Chair of Nephrology, Department of Public Health, Federico II University of Naples, Naples, Italy. 3. Chair of Statistics, Department of Public Health, Federico II University of Naples, Naples, Italy. 4. Department of Pharmacy, School of Medicine and Surgery, Federico II University of Naples, Naples, Italy. 5. Unit of Nephrology, Department of Health Sciences, "Magna Graecia" University, Catanzaro, Italy. 6. Division of Physiology, Department of Clinical Medicine and Surgery, Federico II University of Naples, Naples, Italy. 7. Department of Economics and Law, University of Cassino and Southern Lazio, Cassino, Italy.
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.
RCT Entities:
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 CKDpatients. METHODS: This was a single-blind, randomized placebo-controlled trial (Registration number NCT02199444) carried on 69 CKDpatients (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 CKDpatients in conservative treatment, and confirms its beneficial effects on inflammation and lipid pattern.
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