Cardiovascular disease relates to intestinal uptake of p-cresol in patients with chronic kidney disease.

Abstract

BACKGROUND:

Serum p-cresyl sulfate (PCS) associates with cardiovascular disease in patients with chronic kidney disease. PCS concentrations are determined by intestinal uptake of p-cresol, human metabolism to PCS and renal clearance. Whether intestinal uptake of p-cresol itself is directly associated with cardiovascular disease in patients with renal dysfunction has not been studied to date.

METHODS:

We performed a prospective study in patients with chronic kidney disease stage 1 - 5 (NCT00441623). Intestinal uptake of p-cresol, under steady state conditions, was estimated from 24 h urinary excretion of PCS. Primary endpoint was time to first cardiovascular event, i.e., cardiac death, myocardial infarction/ischemia, ventricular arrhythmia, cardiovascular surgery, ischemic stroke or symptomatic peripheral arterial disease. Statistical analysis was done using Kaplan-Meier estimates and Cox proportional hazard analyses.

RESULTS:

In a cohort of 200 patients, median 24 h urinary excretion of PCS amounted to 457.47 μmol (IQR 252.68 - 697.17). After a median follow-up of 52 months, 25 patients reached the primary endpoint (tertile 1/2/3: 5/6/14 events, log rank P 0.037). Higher urinary excretion of PCS was directly associated with cardiovascular events (univariate hazard ratio per 100 μmol increase: 1.112, P 0.002). In multivariate analysis, urinary excretion of PCS remained a predictor of cardiovascular events, independent of eGFR (hazard ratio 1.120, P 0.002).

CONCLUSIONS:

In patients with chronic kidney disease, intestinal uptake of p-cresol associates with cardiovascular disease independent of renal function. The intestinal generation and absorption of p-cresol may be therapeutic targets to reduce cardiovascular disease risk in patients with renal dysfunction.

• Authors: Ruben Poesen, Liesbeth Viaene, Kristin Verbeke, Patrick Augustijns, Bert Bammens, Kathleen Claes, Dirk Kuypers, Pieter Evenepoel, Björn Meijers
• Journal: BMC nephrology (BMC Nephrol) Vol. 15 Pg. 87 (Jun 09 2014) ISSN: 1471-2369 [Electronic] England
• PMID: 24912660 (Publication Type: Clinical Trial, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• Cresols
• 4-cresol

Topics

• Aged
• Aged, 80 and over
• Belgium (epidemiology)
• Biomarkers (urine)
• Cardiovascular Diseases (diagnosis, epidemiology, urine)
• Comorbidity
• Cresols (pharmacokinetics, urine)
• Female
• Humans
• Incidence
• Intestinal Absorption
• Male
• Middle Aged
• Renal Insufficiency, Chronic (diagnosis, epidemiology, urine)
• Reproducibility of Results
• Risk Factors
• Sensitivity and Specificity