Molecular and cellular pathophysiology of obstructive nephropathy

Congenital obstructive nephropathy remains one of the most-important causes of renal insufficiency in children. This review focuses on the unique inte ractions that result from urinary tract obstruction during the period of re nal development in the neonatal rodent. Following unilateral ureteral obstr uction (UUO), growth of the obstructed kidney is impaired and compensatory growth by the intact opposite kidney is related directly to the duration of obstruction. Development of the renal vasculature is delayed by UUO, and t he activity of the intrarenal renin-angiotensin system is enhanced througho ut the period of obstruction. Glomerular maturation is also delayed by UUO, and nephrogenesis is permanently impaired. The effects of UUO on the devel oping tubule are also profound, with a suppression of proliferation, stimul ation of apoptosis, and the maintenance of an immature phenotype by tubular epithelial cells. Expression of tubular epidermal growth factor is suppres sed and transforming growth factor-beta 1 and clusterin are increased. Matu ration of interstitial fibroblasts is delayed, with progression of tubular atrophy and interstitial fibrosis resulting in part from continued activati on of the renin-angiotensin system and oxygen radicals. Future efforts to p revent the consequences of congenital urinary tract obstruction must accoun t for the dual effects of obstruction: interference with normal renal devel opment and progression of irreversible tubulointerstitial injury.