SEQUELAE OF OBSTRUCTIVE NEPHROPATHY IN THE NEONATE ARE ATTENUATED BY EXOGENOUS EPIDERMAL GROWTH FACTOR (EGF). • 1655

Abstract

Obstructive nephropathy is a primary cause of renal failure in infancy. We have shown previously that chronic unilateral ureteral obstruction (UUO) in the neonatal rat results in delayed renal maturation and reduced renal expression of EGF, as well as tubular cell apoptosis and interstitial fibrosis(J Urol 155:1139, & 156:1474, 1996). To determine whether these changes could be reversed by exogenous administration of EGF, 23 Sprague-Dawley rats underwent UUO within the first 48 h of life, and received daily injections of either EGF (0.1 mg/kg/d) or saline for the following 7 days. Obstructed (UUO) and intact opposite (IO) kidneys were harvested, and the fraction of proliferating cells was determined by PCNA staining, the fraction of apoptotic cells was determined by the TUNEL technique, and tubular atrophy and renal interstitial volume were determined by morphometry. There was no effect of EGF treatment on body weight or kidney weight. Compared to saline, EGF treatment increased tubular cell proliferation by 66% in the UUO kidney, but decreased tubular cell proliferation by 16% in the IO kidney (p<0.05). EGF treatment reduced the fraction of apoptotic tubular epithelial cells by 83%, and reduced the fraction of apoptotic tubules by 78% in the UUO kidney (p<0.05). There was no effect of EGF on interstitial cell apoptosis in the UUO kidney, and no effect on apoptosis in the IO kidney. EGF treatment reduced the fraction of atrophic tubules by 33%, and reduced renal interstitial volume by 55% in the UUO kidney (p<0.05). There was no effect of EGF on tubular atrophy or interstitial volume in the IO kidney. We conclude that EGF stimulates cell proliferation and inhibits tubular cell apoptosis in the neonatal kidney subjected to chronic UUO. These effects may contribute to the reduction in tubular atrophy and interstitial fibrosis. Thus, by preserving renal growth and development, administration of EGF may attenuate renal injury resulting from chronic UUO in early development.