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Endotoxaemia in haemodialysis: a novel factor in erythropoetin resistance?

Harrison, Laura E.A.; Burton, James O.; Szeto, Cheuk-Chun; Li, Philip K.T.; McIntyre, Christopher W.

Authors

Laura E.A. Harrison

James O. Burton

Cheuk-Chun Szeto

Philip K.T. Li

Christopher W. McIntyre

Abstract

Background/Objectives


Translocated endotoxin derived from intestinal bacteria is a driver of systemic inflammation and oxidative stress. Severe endotoxaemia is an underappreciated, but characteristic finding in haemodialysis (HD) patients, and appears to be driven by acute repetitive dialysis induced circulatory stress. Resistance to erythropoietin (EPO) has been identified as a predictor of mortality risk, and associated with inflammation and malnutrition. This study aims to explore the potential link between previously unrecognised endotoxaemia and EPO Resistance Index (ERI) in HD patients.

Methodology/Principal Findings


50 established HD patients were studied at a routine dialysis session. Data collection included weight, BMI, ultrafiltration volume, weekly EPO dose, and blood sampling pre and post HD. ERI was calculated as ratio of total weekly EPO dose to body weight (U/kg) to haemoglobin level (g/dL). Mean haemoglobin (Hb) was 11.3±1.3 g/dL with a median EPO dose of 10,000 [IQR 7,500–20,000] u/wk and ERI of 13.7 [IQR 6.9–23.3] ((U/Kg)/(g/dL)). Mean pre-HD serum ET levels were significantly elevated at 0.69±0.30 EU/ml. Natural logarithm (Ln) of ERI correlated to predialysis ET levels (r = 0.324, p = 0.03) with a trend towards association with hsCRP (r = 0.280, p = 0.07). Ln ERI correlated with ultrafiltration volume, a driver of circulatory stress (r = 0.295, p = 0.046), previously identified to be associated with increased intradialytic endotoxin translocation. Both serum ET and ultrafiltration volume corrected for body weight were independently associated with Ln ERI in multivariable analysis.

Conclusions


This study suggests that endotoxaemia is a significant factor in setting levels of EPO requirement. It raises the possibility that elevated EPO doses may in part merely be identifying patients subjected to significant circulatory stress and suffering the myriad of negative biological consequences arising from sustained systemic exposure to endotoxin.

Journal Article Type Article
Publication Date Jun 29, 2012
Journal PLoS ONE
Electronic ISSN 1932-6203
Publisher Public Library of Science
Peer Reviewed Peer Reviewed
Volume 7
Issue 6
Article Number e40209
Institution Citation Harrison, L. E., Burton, J. O., Szeto, C., Li, P. K., & McIntyre, C. W. (2012). Endotoxaemia in haemodialysis: a novel factor in erythropoetin resistance?. PLoS ONE, 7(6), doi:10.1371/journal.pone.0040209
DOI https://doi.org/10.1371/journal.pone.0040209
Publisher URL http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0040209
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0




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