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

Chan, W., Bosch, J.A., Phillips, A.C., Chin, S.H., Antonysunil, A. ORCID: 0000-0003-2974-3388, Inston, N., Moore, S., Kaur, O., McTernan, P.G. ORCID: 0000-0001-9023-0261 and Borrows, R., 2018. The associations of endotoxemia with systemic inflammation, endothelial activation, and cardiovascular outcome in kidney transplantation. Journal of Renal Nutrition, 28 (1), pp. 13-27. ISSN 1051-2276

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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.

Item Type: Journal article
Publication Title: Journal of Renal Nutrition
Creators: Chan, W., Bosch, J.A., Phillips, A.C., Chin, S.H., Antonysunil, A., Inston, N., Moore, S., Kaur, O., McTernan, P.G. and Borrows, R.
Publisher: W.B. Saunders Co.
Date: January 2018
Volume: 28
Number: 1
ISSN: 1051-2276
Identifiers:
NumberType
10.1053/j.jrn.2017.06.004DOI
S1051227617301462Publisher Item Identifier
Rights: Copyright © 2017 by the National Kidney Foundation, Inc. All rights reserved.
Divisions: Schools > School of Science and Technology
Depositing User: Jonathan Gallacher
Date Added: 25 Jan 2018 12:49
Last Modified: 14 Mar 2018 13:59
URI: http://irep.ntu.ac.uk/id/eprint/32544

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