Renal apoptosis and clusterin following ureteral obstruction: The role of maturation

Purpose: Unilateral ureteral obstruction (UUO) increases renal apoptosis 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, renal apoptosis was quantitated by flow cytometry, and renal messenger RNA (mRNA) was quantitated for renin and clusterin. Apoptotic cells, macrophages, clusterin and Dolichos biflorus agglutinin were localized by immunohistochemistry. Results: Following ipsilateral UUO, renal DNA content increased in the adult but decreased in the neonate. Renal macrophage infiltration induced by UUO was 2-fold greater in adults than in neonates, while distal tubular apoptosis was 2-fold greater in neonatal than in adult kidneys. Unilateral ureteral obstruction markedly increased renal renin mRNA expression in the neonate, but not in the adult, while clusterin expression was greater in adults than in neonates. Clusterin was localized to some, but not all, distal tubules containing apoptotic cells. Conclusions: We conclude that, compared with the adult, UUO in the neonate induces greater apoptosis, which in turn contributes to reduced renal DNA. This may be modulated by relative suppression of clusterin in the obstructed neonatal kidney due to greater activation of the renin-angiotensin system.