Response to growth hormone therapy in experimental ischemic acute renal failure

In acute renal failure (ARF), the gene and peptide expression of insulin-li ke growth factor-I (IGF-I) falls. Because IGF-I is regulated by growth horm one (GH) and because kidney GH receptor expression is also attenuated in AR F, the impaired IGF-I expression may partly reflect local GH resistance. Be cause IGF-I treatment accelerates recovery from ARF, we determined whether high-dose GH therapy could overcome this putative GH resistance, stimulate IGF-I production, and enhance recovery, Rats with ARF were given 2.5 mg GH or vehicle (V) over 2 days, beginning 24 hours before the onset of ARF, GH prevented weight loss but did not modify the course of ARF, Next we determi ned whether the failure of GH to modify kidney recovery could reflect a fai lure to stimulate renal IGF-I gene expression. Rats were treated with GH or V over an 18-hour period beginning 1 day after the induction of ARF, Hepat ic IGF-I mRNA and serum IGF-l peptide levels rose significantly with GH tre atment, but the low kidney IGF-I mRNA levels did not respond. We conclude t hat the failure of GH to enhance recovery from ARF is caused by impaired GH -stimulated renal IGF-I production, while the maintenance of body weight li kely reflects the systemic effects of the increase in hepatic IGF-I product ion.