High dosage growth hormone treatment and post-ischemic acute renal failure in the rat.
The positive effect of insulin-like growth factor I (IGF-I) on the outcome 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 rats suffering from post-ischemic renal failure were treated with high dosage growth hormone (GH). Forty-six rats were subjected to bilateral renal ischemia for 45 min. Following reperfusion the animals were treated with either human recombinant GH in a dosage of 2 mg/day given as subcutaneous injection or placebo. The animals were monitored daily for body weight, s-creatinine, s-urea and B-glucose. S-IGF levels were determined 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 surviving animals at the end of the experiment. Survival in the GH-treated rats was 42.9% as compared to 32.0% in the control group (not significant). 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-creatinine levels tended to be lower in the GH-group at all times studied, but the difference was not significant. The s-urea levels were significantly reduced by GH-treatment at day 2 (P<0.05). GH treatment caused no adverse effects on carbohydrate metabolism as studied by daily B-glucose determinations. The serum IGF-I levels were identical in both the groups at day zero. At day 3 the serum IGF-I levels had increased by approximately 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 placebo group (not significant). When placebo-treated uremic rats were compared 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 resistance syndrome in acute renal failure.
Matejka
G L
GL
Department of Internal Medicine, Research Centre for Endocrinology and Metabolism, University of Göteborg, Sahlgrenska Hospital, Sweden. Goran-matejka@ss.qu.se
Bengtsson
B A
BA
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D004351:Drug Resistance; D013006:Growth Hormone / Q000008:administration & dosage / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D007511:Ischemia / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011986:Receptors, Somatotropin / Q000235:genetics; D015996:Survival Rate; D014508:Urea / Q000097:blood
D001786:Blood Glucose; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D014508:Urea; D013006:Growth Hormone; D003404:Creatinine