title: Hyperglycemic kidney damage in an animal model of prolonged critical illness.
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.
authors.affiliation: Department of Intensive Care Medicine, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Ilse
authors.initials: I
authors.lastname: Vanhorebeek
authors.forename: Jan
authors.initials: J
authors.lastname: Gunst
authors.forename: Björn
authors.initials: B
authors.lastname: Ellger
authors.forename: Magaly
authors.initials: M
authors.lastname: Boussemaere
authors.forename: Evelyne
authors.initials: E
authors.lastname: Lerut
authors.forename: Yves
authors.initials: Y
authors.lastname: Debaveye
authors.forename: Naila
authors.initials: N
authors.lastname: Rabbani
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Thornalley
authors.forename: Miet
authors.initials: M
authors.lastname: Schetz
authors.forename: Greet
authors.initials: G
authors.lastname: Van den Berghe
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D003404:Creatinine / Q000097:blood; D016638:Critical Illness / Q000401:mortality; D004195:Disease Models, Animal; D005947:Glucose / Q000032:analysis; D006019:Glycolysis; D006037:Glyoxal / Q000097:blood; D006943:Hyperglycemia / Q000401:mortality / Q000473:pathology*; D007328:Insulin / Q000097:blood; D007668:Kidney / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008928:Mitochondria / Q000502:physiology; D010100:Oxygen / Q000378:metabolism; D011817:Rabbits
chemical_list: D001786:Blood Glucose; D007328:Insulin; D006037:Glyoxal; D003404:Creatinine; D005947:Glucose; D010100:Oxygen