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Insulin-Like Growth Factor I Accelerates Recovery from Ischemic Acute Tubular Necrosis in the Rat
Steven B. Miller, Daniel R. Martin, John Kissane and Marc R. Hammerman
Proceedings of the National Academy of Sciences of the United States of America
Vol. 89, No. 24 (Dec. 15, 1992), pp. 11876-11880
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/2360819
Page Count: 5
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The effects of administering insulin-like growth factor I (IGF-I) were examined in a model of ischemic acute tubular necrosis in rats. Injury was induced by 75 min of bilateral renal artery occlusion. Compared to rats administered vehicle, rats administered IGF-I (100 μg/day via continuous subcutaneous infusion) had significantly lower serum creatinine and blood urea nitrogen levels over the course of 7 days postocclusion. Glomerular filtration rate as determined by inulin clearance was examined on day 2 postocclusion and was significantly increased in IGF-I-treated animals (0.16 ± 0.02 ml per min per 100 g of body weight) compared to vehicle-treated controls (0.08 ± 0.02 ml per min per 100 g of body weight). The weight loss that occurred during the course of acute tubular necrosis was ameliorated by IGF-I. Mortality was reduced from 36.7% in vehicle-treated rats to 7.1% in rats administered IGF-I. Histologically, there was much less renal injury evident at day 7 postocclusion in the IGF-I-treated rats compared to vehicle-treated controls. In contrast, growth hormone (200 μ g administered subcutaneously for 4 days) did not affect recovery of renal function or reduce mortality postreperfusion. This report demonstrates a beneficial effect of IGF-I administration in the setting of acute tubular necrosis. Several properties of IGF-I render it a pharmacological agent with excellent potential for treatment of this condition in humans.
Proceedings of the National Academy of Sciences of the United States of America © 1992 National Academy of Sciences