EFFECT OF DIETARY-PROTEIN INTAKE ON RENAL GROWTH - POSSIBLE ROLE OF INSULIN-LIKE GROWTH FACTOR-I

Insulin-like growth factor-I (IGF-I) has been implicated as a possible mediator of renal hypertrophy after uninephrectomy and diabetes melli tus. Because renal hypertrophy is also a consequence of high protein i ntake, we studied the effect of varying concentrations of dietary prot ein on circulating levels and renal tissue content of IGF-I. Male Spra gue-Dawley rats were fed isocaloric diets containing high (50%, HP), n ormal (20%, NP) or low (6%, LP) dietary protein for up to 14 days befo re they were killed. As expected, renal size (dry kidney weight) was g reater in HP-fed rats and smaller in LP-fed rats when compared with NP -fed animals (HP, 1415 +/- 26 mg [p < 0.01 vs NP]; NP, 1148 +/- 27 mg; LP, 838 +/- 16 mg [p < 0.01 vs NP]), and most of the relative changes in kidney size occurred during the first week of ingestion of the exp erimental diet. Renal hypertrophy in the HP-fed animals was accompanie d at day 3 by a significant rise in kidney tissue IGF-I that remained elevated at day 7 but had fallen to baseline values by day 14. The ris e in renal IGF-I content in the HP-fed rat was accompanied by increase s in circulating IGF-I on day 3 only. Both circulating and renal tissu e IGF-I levels were suppressed in the LP-fed animals at 3, 7, and 14 d ays. These data confirm that varying dietary protein intake has profou nd effects on both circulating and renal IGF-I levels. They are consis tent with a potential causal role of decreased hepatic and renal IGF-I synthesis in the blunted somatic and renal growth that is seen in the LP-fed rat. The data from the HP-fed animals also suggest that increa sed renal synthesis of IGF-I may play an important role in the initial hypertrophic response seen in response to an HP diet. However, persis tent elevation of circulating or kidney IGF-I levels (or both) does no t appear necessary for the maintenance of kidney hypertrophy in the HP -fed rat.