HIGH DOSAGE GROWTH-HORMONE TREATMENT AND POSTISCHEMIC ACUTE-RENAL-FAILURE IN THE RAT

The positive effect of insulin-like growth factor I (IGF-I) on the out come of experimental acute renal failure has gained much attention in recent years. However, the potential positive effects of GH have been less intensively studied. Therefore, a study was designed in which rat s suffering from post-ischemic renal failure were treated with high do sage growth hormone (GH). Forty-six rats were subjected to bilateral r enal ischemia for 45 min. Following reperfusion the animals were treat ed with either human recombinant GH in a dosage of 2 mg/day given as s ubcutaneous injection or placebo. The animals were monitored daily for body weight, s-creatinine, s-urea and B-glucose. S-IGF levels were de termined at the start of the experiment and at days 3 and 7. IGF-I and GH receptor mRNA were measured in the kidney and the liver of the sur viving animals at the end of the experiment. Survival in the GH-treate d rats was 42.9% as compared to 32.0% in the control group (not signif icant). Both groups of animals lost body weight in the initial phase. The loss in body weight was less pronounced for the GH-treated animals and the difference was significant at day 2 (P<0.05). The s-creatinin e levels tended to be lower in the GH-group at all times studied, but the difference was not significant. The s-urea levels were significant ly reduced by GH-treatment at day 2 (P<0.05). GH treatment caused no a dverse effects on carbohydrate metabolism as studied by daily B-glucos e determinations. The serum IGF-I levels were identical in both the gr oups at day zero. At day 3 the serum IGF-I levels had increased by app roximately 30% in both groups. At day 7 the serum IGF-I level was 1600 ng/ml in the GH-treated group as compared to 1400 ng/ml in the placeb o group (not significant). When placebo-treated uremic rats were compa red to normal sham-operated animals GH-rec mRNA was down-regulated in the kidney and liver, while IGF-I mRNA was down-regulated only in the liver (P<0.05). GH treatment partly restored the GH-rec and IGF-I mRNA levels in both organs. The data are compatible with a severe GH resis tance syndrome in acute renal failure. (C) 1998 Churchill Livingstone