Endotoxaemia in haemodialysis: a novel factor in erythropoetin resistance?

<h4>Background/objectives</h4>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 repeti...

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Autores principales:	Laura E A Harrison, James O Burton, Cheuk-Chun Szeto, Philip K T Li, Christopher W McIntyre
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/184bccc7445f444d821ef9cc5133951f
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spelling	oai:doaj.org-article:184bccc7445f444d821ef9cc5133951f2021-11-18T07:13:39ZEndotoxaemia in haemodialysis: a novel factor in erythropoetin resistance?1932-620310.1371/journal.pone.0040209https://doaj.org/article/184bccc7445f444d821ef9cc5133951f2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22768256/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background/objectives</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions</h4>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.Laura E A HarrisonJames O BurtonCheuk-Chun SzetoPhilip K T LiChristopher W McIntyrePublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 6, p e40209 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Laura E A Harrison James O Burton Cheuk-Chun Szeto Philip K T Li Christopher W McIntyre Endotoxaemia in haemodialysis: a novel factor in erythropoetin resistance?
description	<h4>Background/objectives</h4>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.<h4>Methodology/principal findings</h4>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.<h4>Conclusions</h4>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.
format	article
author	Laura E A Harrison James O Burton Cheuk-Chun Szeto Philip K T Li Christopher W McIntyre
author_facet	Laura E A Harrison James O Burton Cheuk-Chun Szeto Philip K T Li Christopher W McIntyre
author_sort	Laura E A Harrison
title	Endotoxaemia in haemodialysis: a novel factor in erythropoetin resistance?
title_short	Endotoxaemia in haemodialysis: a novel factor in erythropoetin resistance?
title_full	Endotoxaemia in haemodialysis: a novel factor in erythropoetin resistance?
title_fullStr	Endotoxaemia in haemodialysis: a novel factor in erythropoetin resistance?
title_full_unstemmed	Endotoxaemia in haemodialysis: a novel factor in erythropoetin resistance?
title_sort	endotoxaemia in haemodialysis: a novel factor in erythropoetin resistance?
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/184bccc7445f444d821ef9cc5133951f
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Endotoxaemia in haemodialysis: a novel factor in erythropoetin resistance?

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