The Associations of Endotoxemia With Systemic Inflammation, Endothelial Activation, and Cardiovascular Outcome in Kidney Transplantation

Abstract

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. This is a single-center cross-sectional study with prospective follow-up from a prevalent cohort of 128 KTRs. 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. 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). 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.