The effect of betamethasone exposure in mid‐gestation on renal function in adult sheep

Abstract

Prenatal exposure of male or female ovine fetuses to clinically relevant doses of glucocorticoids during the time of peak nephrogenesis results in a reduction in nephron number in adulthood. In the present study, we evaluated the effect of exposure to betamethasone at 80–81 days of gestation on renal function in 16 ewes and 15 rams at 1.5 years of age. After 5–7 days of recovery from surgery for placement of vascular and bladder catheters, glomerular filtration rate (GFR), estimated as clearance of inulin and renal plasma flow (RPF) determined by clearance of p-aminohppuric acid (PAH) were assayed by an initial loading dose followed with constant intravenous (i.v.) infusion of 0.9% sterile saline containing inulin and PAH. An acute sodium load was administrated by a continuous infusion of hypertonic NaCl (0.0375 mEq/Kg/min at 0.55 ml/min for 60 minutes) within the period of PAH/inulin infusion. Inulin clearance significantly decreased in male prenatal betamethasone exposed adults (154±18 ml/min) compared with male controls (213±18 ml/min) (P<0.05). The PAH clearance was significantly lower in male prenatal betamethasone exposed group (883±65 ml/min) than controls (1079±30 ml/min) (P<0.05). These differences were also present after normalization by body surface area (P<0.02). In contrast, the inulin and PAH clearances were similar in control and steroid exposed females. Significant increments in inulin/PAH clearance with an acute sodium load were observed in male betamathasone exposed sheep only. These data suggest that prenatal exposure to glucocorticoids alters renal function in adult male sheep by potentially decreasing GFR and RPF and that females are protected from this steroid-induced effect. (Supported by NIH grants HD 47584, HL 68728 and HD 17644.)