The associations of Endotoxemia with systemic inflammation, endothelial activation, and cardiovascular outcome in kidney transplantation

Research output: Contribution to journalArticle

Authors

  • Winnie Chan
  • Shui Hao Chin
  • Adaikala Antonysunil
  • Nicholas Inston
  • Sue Moore
  • Okdeep Kaur
  • Philip G. McTernan
  • Richard Borrows

External organisations

  • Queen Elizabeth Hospital, University Hospital Birmingham NHS Foundation Trust
  • Department of Clinical Psychology
  • UNIVERSITY OF AMSTERDAM
  • University of Leicester
  • Warwick Medical School
  • Hammersmith Hospital
  • Department of Nephrology & Kidney Transplantation
  • Centre for Translational Inflammation Research; Rheumatology Research Group; University of Birmingham; Birmingham UK

Abstract

Objective Cardiovascular disease is the leading cause of death in kidney transplant recipients (KTRs), yet incompletely accountable by traditional risk factors. Inflammation is an unconventional cardiovascular risk factor, with gut-derived endotoxemia potentially driving inflammation and endothelial disease. Comparable data are lacking in kidney transplantation. This study investigated the associations of endotoxemia with inflammation, endothelial activation, and 5-year cardiovascular events in KTRs. Determinants of endotoxemia were also explored. Design and Methods This is a single-center cross-sectional study with prospective follow-up from a prevalent cohort of 128 KTRs. Main Outcome Measures Demographic, nutritional and clinical predictors of inflammation (high-sensitivity C-reactive protein [hsCRP]), endothelial activation (sE-selectin), and endotoxemia (endotoxin) were assessed. Follow-up data on 5-year cardiovascular event rates were collected. Results Endotoxemia (P =.03), reduced 25-hydroxyvitamin D (P =.04), high fructose intake (P <.001), decreased fiber intake (P <.001), and abdominal obesity (P =.002) were independently associated with elevated hsCRP. In turn, endotoxemia (P =.007) and increasing hsCRP (P =.02) were both independently associated with raised sE-selectin. Furthermore, endotoxemia predicted increased cardiovascular event rate (P =.02), independent of hsCRP and a global measure of cardiovascular risk estimated by a validated algorithm of 7-year risk for major adverse cardiac events in kidney transplantation. Determinants of endotoxemia included reduced 25-hydroxyvitamin D (P <.001), hypertriglyceridemia (P <.001), increased fructose intake (P =.01), and abdominal obesity (P =.01). Conclusions Endotoxemia in KTRs contributes to inflammation, endothelial activation, and increased cardiovascular events. This study highlights the clinical relevance of endotoxemia in KTRs, suggesting future interventional targets.

Details

Original languageEnglish
Pages (from-to)13-27
Number of pages15
JournalJournal of Renal Nutrition
Volume28
Issue number1
Early online date28 Oct 2017
Publication statusPublished - 1 Jan 2018