Abstract
Renal insufficiency as a result of congenital obstructive nephropathy is a consequence of impaired renal growth: chronic unilateral ureteral obstruction (UUO) results in greater injury to the immature kidney than to the adult kidney. The neonatal kidney responds to UUO by marked activation of the renin-angiotensin system, which contributes to severe vasoconstriction and progressive interstitial fibrosis of the obstructed kidney. The latter results in part because of activation of transforming growth factor-beta 1 by angiotensin II. Chronic UUO in the neonatal rat delays maturation of the obstructed kidney, possibly in part through suppressed expression of epidermal growth factor. In addition to affecting growth factors, UUO stimulates apoptosis in the obstructed kidney, which is quantitatively greater in the neonate than in the adult. In contrast, expression of clusterin, a glycoprotein that may play a protective role in the response to UUO, is greater in the adult than in the neonatal obstructed kidney. The response of the developing kidney to UUO is similar in a number of respects to cystic kidney disease. This includes a reduction in epidermal growth factor, and increased apoptosis that may result from suppression of bcl-2, an oncoprotein that inhibits apoptosis. Improved knowledge of the cellular and molecular basis for cystic renal disorders should lead to specific intervention in fetuses and infants with congenital obstructive nephropathy, thereby improving renal growth and development.
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