INDUCTION OF HEAT-SHOCK PROTEINS DOES NOT PREVENT RENAL TUBULAR INJURY FOLLOWING ISCHEMIA

The possible protective effect of heat-shock proteins (HSPs) on ischem ic injury to renal cells was assessed in two different experimental mo dels: ischemia-reflow in intact rats and medullary hypoxic injury as s een in the isolated perfused rat kidney. Heat shock was induced by rai sing the core temperature of rats to 42 degrees C for 15 minutes. Foll owing this, Northern blots showed enhanced gene expression of HSP70, H SP60 and ubiquitin at one hour and reaching a maximum by six hours aft er heat shock in all regions of the kidney, but most prominently in me dulla and papilla. The HSP70 protein in the kidney, estimated by immun ohistochemical means, was detectable 74 hours following heat shock and further increased at 48 hours following heat shock. In the first set of experiments, the animals underwent uninephrectomy followed by cross clamping of the remaining renal artery for 40 minutes prior to reflow . Serum creatinine and urea nitrogen rose to 3.15 +/- 0.98 and 126.4 /- 62.5 mg/dl at 24 hours. No significant differences were observed at 24, 48 and 72 hours after reflow between these values in central rats and rats pretreated with heat shock 48 hours earlier. Severe morpholo gical damage to proximal tubules of the renal cortex was observed to t he same extent in both groups. In a second set of experiments, the rig ht kidney was removed either 24 or 48 hours after heat shock and perfu sed in isolation for 90 minutes. Functional and morphological paramete rs were compared with those of isolated perfused kidneys obtained from animals that had not been subjected to heat shock. No difference was observed in the degree or extent of hypoxic injury to the medullary th ick ascending limb, characteristically observed in the isolated perfus ed rat kidney, nor did prior induction of HSPs modify the progressive decline in glomerular filtration rate or fractional reabsorption of gl ucose seen in perfused kidneys. Fractional reabsorption of sodium was slightly higher in kidneys from rats earlier exposed to heat shock. Th ese results do not support the hypothesis that heat shock proteins pre vent ischemic renal injury.