RAT MODELS FOR CLINICAL USE OF INSULIN-LIKE GROWTH-FACTOR-I IN ACUTE-RENAL-FAILURE

Insulin-like growth factor I (IGF-I) improves kidney function and histopathology, when given within a short time (0.5 or 5 h) after an ischemic renal insult in rats. To examine the effects of IGF-I at times that would be more applicable if it were to be used as a therapeutic agent for acute renal failure in humans, we administered IGF-I to rats 24 h after ischemic injury or prior to the induction of injury (pretreatment). In rats that received IGF-I 24 h postischemia, serum creatinine and blood urea nitrogen (BUN) values were significantly lower during the subsequent 6 days than in vehicle-treated rats, and incorporation of 5-bromo-2'-deoxyuridine into tubular cells of the regenerating cortex, measured 48 h postischemia, was enhanced. When examined 7 days postinjury, kidneys from rats that received IGF-I 24 h postischemia were improved in histopathological appearance compared with kidneys from vehicle-treated animals. Whereas creatinine and BUN values were elevated above baseline in both vehicle and IGF-I-pretreated groups, recovery of normal renal function was accelerated by pretreatment with IGF-I. In addition, although we could detect no differences in histopathology at 24 h postinjury, IGF-I pretreatment resulted in more normal renal histology at 7 days postischemic injury and reduced weight loss after injury. Our data show that IGF-I hastens recovery and accelerates regeneration or repair of damaged epithelia following acute renal failure in rats when administered either 24 h postinjury or prior to induction of acute renal failure. These findings establish the potential for clinical use of IGF-I as a therapy for established acute renal failure or as a prophylactic agent to ameliorate the course of renal failure subsequent to ischemic injury.