RENAL APOPTOSIS AND CLUSTERIN FOLLOWING URETERAL OBSTRUCTION - THE ROLE OF MATURATION

Purpose: Unilateral ureteral obstruction (UUO) increases renal apoptos is as well as clusterin, which in turn is modulated by angiotensin II. The present study was designed to investigate the role of maturation in these responses. Materials and Methods: Neonatal and adult Sprague- Dawley rats underwent UUO or sham operation. Fourteen days later, rena l apoptosis was quantitated by flow cytometry, and renal messenger RNA (mRNA) was quantitated for renin and clusterin. Apoptotic cells, macr ophages, clusterin and Dolichos biflorus agglutinin were localized by immunohistochemistry. Results: Following ipsilateral UUO, renal DNA co ntent increased in the adult but decreased in the neonate. Renal macro phage infiltration induced by UUO was 2-fold greater in adults than in neonates, while distal tubular apoptosis was 2-fold greater in neonat al than in adult kidneys. Unilateral ureteral obstruction markedly inc reased renal renin mRNA expression in the neonate, but not in the adul t, while clusterin expression was greater in adults than in neonates. Clusterin was localized to some, but not all, distal tubules containin g apoptotic cells. Conclusions: We conclude that, compared with the ad ult, UUO in the neonate induces greater apoptosis, which in turn contr ibutes to reduced renal DNA. This may be modulated by relative suppres sion of clusterin in the obstructed neonatal kidney due to greater act ivation of the renin-angiotensin system.