Association between Protein-Bound Uremic Toxins and Asymptomatic Cardiac Dysfunction in Patients with Chronic Kidney Disease.

Shanmugakumar Chinnappa,Yi Chun Yeh,Griet Glorieux,Raymond Vanholder,Yu-Kang Tu,Andrew Mooney

doi:10.3390/toxins10120520

Abstract

Although the relationship between protein-bound uremic toxins (PBUTs) and cardiac structure and cardiac mortality in chronic kidney disease (CKD) has been studied in the past, the association between cardiac dysfunction and PBUTs has not yet been studied. We therefore evaluated the association between impaired peak cardiac performance and the serum free and total concentrations of potentially cardiotoxic PBUTs. In a cross-sectional study of 56 male CKD patients (stages 2–5 (pre-dialysis)) who were asymptomatic with no known cardiac diseases or diabetes we measured peak cardiac power (CPOmax), aerobic exercise capacity (VO2max), and echocardiographic parameters of cardiac morphology and evaluated their association with PBUTs. The serum total and free concentrations of indoxyl sulfate (IXS), p-cresyl sulfate (PCS), p-cresyl glucuronide, indole acetic acid, and hippuric acid showed significant negative correlation with CPOmax and VO2max. IXS and PCS were independently associated with CPOmax and VO2max even after controlling for eGFR. No correlation between left ventricular mass index (LVMI) and PBUTs was seen. The present study for the first time has demonstrated the association between subclinical cardiac dysfunction in CKD and serum levels of a panel of PBUTs. Further studies are required to evaluate the mechanism of cardiotoxicity of the individual uremic toxins.

Highlights

Cardiovascular disease (CVD) is the predominant cause of mortality and morbidity in chronic kidney disease (CKD) and end-stage renal disease (ESRD)
This study demonstrated for the first time the association between protein-bound uremic toxins and subclinical cardiac dysfunction in CKD
Of the 30 or more protein-bound uremic toxins that have previously been reported [1], we tested the leading candidates that might be cardiotoxic, and we found that both free Indoxyl sulfate (IXS) and free p-cresyl sulfate (PCS) were independently and significantly associated with subclinical cardiac dysfunction in CKD

Summary

Introduction

Cardiovascular disease (CVD) is the predominant cause of mortality and morbidity in chronic kidney disease (CKD) and end-stage renal disease (ESRD). Several pathophysiological mechanisms are being studied to understand the mechanism of CVD in CKD. Among the potentially putative agents of CVD in CKD, there is a growing interest in the role of protein-bound uremic toxins (PBUTs) [1,2]. Toxins 2018, 10, 520 range of toxicity such as endothelial dysfunction, vascular calcification, and induction of oxidative stress [3,4,5,6,7]. Clinical studies have shown that some of the PBUTs are associated with cardiovascular and all-cause mortality [5,8]. The association between cardiac dysfunction and PBUTs has not yet been studied

Methods

Results

Conclusion