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.(ABSTRACT TRUNCATED AT 250 WORDS)
Miller
S B
SB
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
Martin
D R
DR
Kissane
J
J
Hammerman
M R
MR
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage / Q000627:therapeutic use*; D007511:Ischemia / Q000150:complications; D007668:Kidney / Q000473:pathology; D007684:Kidney Tubules / Q000187:drug effects; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012038:Regeneration; D012079:Renal Circulation
D007334:Insulin-Like Growth Factor I