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Somatic and renal effects of growth hormone in rats with chronic renal failure
H Kawaguchi1, M Hattori, K Ito
1Department of Pediatric Nephrology, Tokyo, Women's Medical College, Japan.
Insights
Recombinant human growth hormone (rhGH) improves growth in chronic renal failure (CRF) rats but high doses worsen kidney function and structure. This effect appears direct, not mediated by insulin-like growth factors.
Area of Science:
- Nephrology
- Endocrinology
- Pediatric Endocrinology
Background:
- Recombinant human growth hormone (rhGH) is used for growth in children with chronic renal failure (CRF).
- Concerns exist that rhGH may accelerate renal disease progression.
Purpose of the Study:
- To investigate the effects of prolonged rhGH administration on somatic growth, renal function, and renal structure in rats with CRF.
Main Methods:
- Rats with CRF were divided into four groups receiving different doses of rhGH (vehicle, 0.4, 2.0, 10.0 IU/day) subcutaneously for 8 weeks.
- Somatic growth, body weight, body length, creatinine clearance, glomerular sclerosing index, and urinary protein excretion were assessed.
- Renal and circulating insulin-like growth factor (IGF) levels were measured.
Main Results:
- rhGH significantly improved somatic growth, particularly at high doses.
- Creatinine clearance decreased dose-dependently with rhGH administration.
- Glomerular sclerosis worsened with higher rhGH doses, indicating renal structure deterioration.
- Proteinuria showed a trend towards increase with higher rhGH doses.
- Neither renal IGF-I nor circulating IGF-I/IGF-II levels differed significantly among groups.
Conclusions:
- rhGH effectively improves somatic growth in CRF rats.
- Prolonged rhGH administration dose-dependently impairs renal function and structure in CRF rats.
- The observed renal deterioration appears to be a direct effect of rhGH, independent of IGF pathways.
Abstract:
Recombinant human growth hormone (rhGH) has been widely used to improve growth in children with chronic renal failure (CRF). However, there has been great concern that GH may aggravate renal disease and hasten the progression to end-stage renal failure. We therefore investigated the effect of prolonged administration of rhGH at various doses on somatic growth and renal function and structure in rats with CRF, divided into four groups based on rhGH dose (vehicle, 0.4, 2.0, and 10.0 IU/day). rhGH was administered subcutaneously daily for 8 weeks. The mean growth was significantly greater in rats treated with high-dose rhGH (10.0 IU) than those treated with low-dose rhGH (P = 0.0089) or vehicle (P = 0.0011). Body weight gain increased in parallel with body length (Creatinine clearance at the end of the experiment was significantly lower in rats on high or medium-dose rhGH than those on low-dose rhGH and controls (P < 0.05). The glomerular sclerosing index was greater in rats treated with higher doses of rhGH. There were significant differences between rats treated with high-dose rhGH and controls (P = 0.0144) and also between rats on medium-dose rhGH and controls (P = 0.0065). Although there was no significant difference, rats treated with higher doses of rhGH tended to excrete more protein. Renal insulin-like growth factor-I (IGF-I) content and circulating IGF-I and IGF-II levels did not significantly differ among groups. We conclude that: (1) GH improves somatic growth failure in rats with CRF, but prolonged administration of GH dose-dependently induces deterioration in renal function and structure and (2) this effect was induced neither via circulating IGF-I and IGF-II nor by local production of IGF-I, but seems to be direct.