Transient hyperglycemia affects the extent of ischemia-reperfusion-induced renal injury in rats.
BACKGROUND
Chronic hyperglycemia is known to increase renal injury, particularly during ischemia-reperfusion episodes. The goal of this study was to examine whether transient hyperglycemia during or after renal ischemia-reperfusion increased renal dysfunction.


METHODS
Male Lewis rats underwent sham operations or unilateral nephrectomies followed by contralateral renal ischemia-reperfusion. Hyperglycemic rats were given 25% dextrose to induce transient hyperglycemia lasting throughout the duration of ischemia (PI rats) or beginning 2 h after initiation of reperfusion (PR rats). Additional vehicle control rats received saline and underwent ischemia-reperfusion surgery as with PI and PR rats. Twenty-five minutes of mild renal ischemia followed by 24 h of reperfusion was induced by occluding the renal artery and vein.


RESULTS
Terminal serum creatinine concentrations were significantly higher in the PI rats when compared with the PR or vehicle control rats. Histology demonstrated significantly increased necrosis in the PI rats relative to PR and control animals. Tissue analyses demonstrated significantly higher heat shock protein 70, heat shock protein 32, and cleaved caspase-3 protein levels in the PI rats. Oxidative stress generated through the xanthine pathway in the PI group was significantly increased compared with the oxidative stress in the PR and vehicle control rats. In contrast, vascular endothelial growth factor and erythropoietin were significantly decreased in the PI rats compared with the PR rats and controls.


CONCLUSIONS
Hyperglycemia that occurred during renal ischemia-reperfusion resulted in severe functional injury compared with normoglycemia or with hyperglycemia that occurred after reperfusion. Investigated molecular pathways are more profoundly affected by hyperglycemia that occurs before renal ischemia-reperfusion.
Hirose
Ryutaro
R
Department of Surgery, Divisionof Transplantation, University of California, San Francisco, California 94143-0648, USA.
Xu
Fengyun
F
Dang
Kim
K
Liu
Tao
T
Behrends
Matthias
M
Brakeman
Paul R
PR
Wiener-Kronish
Jeanine
J
Niemann
Claus U
CU
D000818:Animals; D006943:Hyperglycemia / Q000097:blood / Q000150:complications / Q000473:pathology*; D007668:Kidney / Q000098:blood supply* / Q000473:pathology*; D008297:Male; D051381:Rats; D011917:Rats, Inbred Lew; D015427:Reperfusion Injury / Q000097:blood / Q000209:etiology / Q000473:pathology*