In the adult, insulin-like growth factor I (IGF-I) increases glomerular filtration rate (GFR) and renal blood flow (RBF) during both acute and chronic treatment. To study its effects on the developing kidney, chronically catheterized fetal sheep (120 ± 1 days gestation) were infused intravenously for up to 10 days with 80 μg/h IGF-I ( n = 5) or vehicle (0.1% BSA in saline, n = 6). In contrast to previous acute studies in adult rats and humans, after 4 h of IGF-I fetal GFR and RBF were unchanged. Fractional sodium reabsorption increased ( P< 0.05). However, by 4 days, GFR per kilogram had risen by 35 ± 13% ( P < 0.05), whereas RBF remained unchanged. Tubular growth and maturation may have occurred, as proximal tubular sodium reabsorption increased by ∼35% ( P < 0.005). Therefore, despite a marked increase in filtered sodium (∼30%, P < 0.05), fractional sodium reabsorption did not change. Although the effects of IGF-I on renal function were delayed, plasma renin activity and concentration were both elevated after 4 h and remained high at 4 days ( P < 0.05). Despite this, arterial pressure and heart rate did not change. Kidneys of IGF-I-infused fetuses weighed ∼30% more ( P = 0.05) and contained ∼75% more renin than control fetuses ( P < 0.005). Thus, in the fetus, the renal effects of long-term IGF-I infusion are very different from the adult, possibly because IGF-I stimulated kidney growth.
Effects of Age, Sex and Renal Function on Urinary Insulin-Like Growth Factor I(IGF-I) Levels in Adults.
