Vanhorebeek, Ilse, Gunst, Jan, Ellger, Bjoern, Boussemaere, Magaly, Lerut, Evelyne, Debaveye, Yves, Rabbani, Naila, Thornalley, Paul J., Schetz, Miet and Van den Berghe, Greet (2009) Hyperglycemic kidney damage in an animal model of prolonged critical illness. In: 90th Annual Meeting of the Endocrine-Society, San Francisco, CA, June 15-18, 2008. Published in: Kidney International, Vol.76 (No.5). pp. 512-520.

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Abstract

Acute kidney injury frequently complicates critical illness and increases mortality; maintaining normoglycemia with insulin has been shown to reduce the incidence of intensive care unit (ICU)-acquired kidney injury. Here we tested the mechanisms by which this intervention might achieve its goal, using a rabbit model of burn-induced prolonged critical illness in which blood glucose and insulin were independently regulated at normal or elevated levels. Hyperglycemia caused elevated plasma creatinine and severe morphological kidney damage that correlated with elevated cortical glucose levels. Renal cortical perfusion and oxygen delivery were lower in hyperglycemic/hyperinsulinemic rabbits, compared to other groups, but this did not explain the elevated creatinine. Mitochondrial respiratory chain activities were severely reduced in the hyperglycemic groups (30-40% residual activity), and were inversely correlated with plasma creatinine and cortical glucose. These activities were much less affected by normoglycemia, and hyperinsulinemia was not directly protective. Mitochondrial damage, evident at day 3, preceded the structural injury evident at 7 days. Our study found that hyperglycemia evoked cellular glucose overload in the kidneys of critically ill rabbits, and this was associated with mitochondrial dysfunction and renal injury. Normoglycemia, independent of insulinemia, protected against this damage.

Item Type:	Conference Item (Paper)
Subjects:	R Medicine > RC Internal medicine
Divisions:	Faculty of Medicine > Warwick Medical School > Metabolic and Vascular Health Faculty of Medicine > Warwick Medical School
Journal or Publication Title:	Kidney International
Publisher:	Nature Publishing Group
ISSN:	0085-2538
Date:	September 2009
Volume:	Vol.76
Number:	No.5
Number of Pages:	9
Page Range:	pp. 512-520
Identification Number:	10.1038/ki.2009.217
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
Funder:	Fund for Scientific Research (FWO, Research Council of the Katholieke Universiteit Leuven, KULeuven Research Council Postdoctoral Fellowships, FWO Research Assistant Fellowship, Innovative Medizinische Forschung, B Braun, Germany, British Heart Foundation Research Fellowship
Grant number:	G.0533.06; GOA2007/14; EL 610304
Conference Paper Type:	Paper
Title of Event:	90th Annual Meeting of the Endocrine-Society
Type of Event:	Conference
Location of Event:	San Francisco, CA
Date(s) of Event:	June 15-18, 2008
URI:	http://wrap.warwick.ac.uk/id/eprint/17451

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