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

Toxins (Basel). 2018 Dec 5;10(12):520. 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.

Keywords: aerobic exercise capacity; cardiac function; cardiac power; uremic toxins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Arterial Pressure
  • Cardiac Output
  • Cresols / blood
  • Exercise
  • Glucuronides / blood
  • Heart Diseases* / blood
  • Heart Diseases* / physiopathology
  • Heart Rate
  • Hippurates / blood
  • Humans
  • Indican / blood
  • Indoleacetic Acids / blood
  • Male
  • Middle Aged
  • Renal Insufficiency, Chronic* / blood
  • Renal Insufficiency, Chronic* / physiopathology
  • Sulfuric Acid Esters / blood
  • Toxins, Biological / blood*
  • Uremia* / blood
  • Uremia* / physiopathology

Substances

  • 4-cresylglucuronide
  • Cresols
  • Glucuronides
  • Hippurates
  • Indoleacetic Acids
  • Sulfuric Acid Esters
  • Toxins, Biological
  • 4-cresol sulfate
  • indoleacetic acid
  • Indican
  • hippuric acid