Effects of prolonged growth hormone administration in rats with chronic renal insufficiency

Recombinant hGH (rhGH) augments short-term linear growth in experimental animals and children with chronic renal failure. Significant augmentation of final height, however, requires prolonged growth hormone therapy during years of growth. The effects of prolonged rhGH treatment on linear growth, progression of renal dysfunction, and longevity in the setting of renal insufficiency are unknown. We examined at 9, 15, and 25 wk growth in length and weight, glomerular filtration rate measured by inulin and creatinine clearance, food efficiency (g ingested/ weight gained), and survival in treated (U-GH) and untreated (U) 75% nephrectomized uremic rats and in treated (S-GH) and untreated (S) sham-operated rats. We also measured kidney weight to body weight ratios at the time the rats were killed. Treatment was rhGH 1.0 mg s.c. three times a week during wks 4-12 of life. Length of U-GH rats was greater than that of U rats (p < 0.05) at 15 and 25 wk (but not at 9 wk) and equal to that of S rats throughout the study. Length of S-GH rats exceeded that of S rats. At 9 wk, weight was diminished in both U and U-GH rats (p < 0.05) versus S and S-GH rats; by 15 wk, U-GH rat weight was equal to S rat weight. Glomerular filtration rate measured by creatinine was markedly reduced in U and U-GH rats and did not increase in response to prolonged rhGH in either U-GH or S-GH rats. Diminished food efficiency of U rats versus S rats (p < 0.05) was not improved significantly by rhGH. Mortality from chronic renal failure was eight of 19 (42%) in U-GH rats compared with four of 13 (31%) in U rats. Both mean glomerular area and sclerotic index were increased in U-GH rats versus U rats (p < 0.05). The growth-promoting effect of rhGH was observed late (rather than early) in the growth period. Prolonged rhGH treatment did result in UGH rats attaining length and weight comparable to S rats, ameliorating the growth failure due to uremia. Glomerular filtration rate was not adversely affected by prolonged rhGH treatment, and there appeared to be significant renal growth with growth hormone administration as measured by kidney weight/body weight ratio. Survival data, however, suggest that the growth-stimulating effect of rhGH in uremic animals may be accompanied by a trend toward reduced longevity, and histologic evaluation revealed increased glomerular hypertrophy and glomerulosclerosis in both normal and uremic rats treated with rhGH.