Is ischemic preconditioning of the kidney clinically relevant?
BACKGROUND
Renal ischemic preconditioning (IPC) is a phenomenon whereby a brief period of ischemia and reperfusion (I/R) provides tolerance to subsequent periods of ischemia. IPC has been demonstrated to protect rodent kidneys during I/R. The applicability to large mammals, including human beings, is unclear. The objective of this study was to determine if renal IPC has a beneficial effect in a large animal model of warm I/R and hypothermic preservation injury, which occurs with renal allografting.


METHODS
Renal ischemia (45 minutes) and reperfusion was studied in untreated dogs and in dogs receiving IPC (10-minute/10-minute I/R). IPC was administered immediately before I/R (early IPC) or 24 hours before I/R (delayed IPC). In another group of dogs, pharmacologically induced IPC was attempted with local intra-arterial administration of dipyridamole (2.4 mg/kg/min) to increase local adenosine concentrations. Finally, IPC was induced in kidneys before harvest, cold stored for 24 hours in University of Wisconsin flush solution, and subsequently reperfused for 4 hours in allogeneic recipients. Renal functional parameters, including vascular resistance, glomerular filtration rate, urine production, oxygen consumption, and proximal tubular fluid reabsorption, were monitored during the reperfusion period and were compared with the control ischemic group.


RESULTS
Renal function significantly declined during I/R, relative to the nonischemic contralateral kidney but was not different with any form of IPC, relative to the ischemic control group not treated with IPC. IPC pretreatment also did not affect the preservation injury observed in cold-stored kidneys reperfused after transplantation.


CONCLUSIONS
It is concluded that IPC has no significantly measurable effects in warm or hypothermic renal I/R injury in large animals. The clinical usefulness of IPC in human renal ischemic conditions remains uncertain.
Kosieradzki
Maciej
M
Department of Surgery, Division of Transplantation, University of Wisconsin School of Medicine, Madison, Wis, USA.
Ametani
Mary
M
Southard
James H
JH
Mangino
Martin J
MJ
D000818:Animals; D003080:Cold Temperature; D004176:Dipyridamole / Q000494:pharmacology; D004195:Disease Models, Animal; D004285:Dogs; D005919:Glomerular Filtration Rate; D006358:Hot Temperature; D019194:Ischemic Preconditioning; D016030:Kidney Transplantation; D007687:Kidney Tubules, Proximal / Q000098:blood supply / Q000502:physiology*; D008297:Male; D015427:Reperfusion Injury / Q000503:physiopathology*; D014655:Vascular Resistance; D014665:Vasodilator Agents / Q000494:pharmacology
D014665:Vasodilator Agents; D004176:Dipyridamole