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 interactions that result from urinary tract obstruction during the period of renal development in the neonatal rodent. Following unilateral ureteral obstruction (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 the activity of the intrarenal renin-angiotensin system is enhanced throughout the period of obstruction. Glomerular maturation is also delayed by UUO, and nephrogenesis is permanently impaired. The effects of UUO on the developing tubule are also profound, with a suppression of proliferation, stimulation of apoptosis, and the maintenance of an immature phenotype by tubular epithelial cells. Expression of tubular epidermal growth factor is suppressed and transforming growth factor-beta1 and clusterin are increased. Maturation of interstitial fibroblasts is delayed, with progression of tubular atrophy and interstitial fibrosis resulting in part from continued activation of the renin-angiotensin system and oxygen radicals. Future efforts to prevent the consequences of congenital urinary tract obstruction must account for the dual effects of obstruction: interference with normal renal development and progression of irreversible tubulointerstitial injury.
Chevalier
R L
RL
Department of Pediatrics, Box 386, University of Virginia, Health Sciences Center, Charlottesville, VA 22908, USA, rlc2m@Virginia.edu
D000818:Animals; D001808:Blood Vessels / Q000254:growth & development; D004815:Epidermal Growth Factor / Q000378:metabolism; D007668:Kidney / Q000098:blood supply / Q000254:growth & development; D007674:Kidney Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012084:Renin-Angiotensin System / Q000502:physiology; D014517:Ureteral Obstruction / Q000150:complications*
D004815:Epidermal Growth Factor