Pathogenesis of renal injury in obstructive uropathy

Purpose of review focuses on recent advances in understanding the factors contributing to obstructive nephropathy, the most important cause of renal failure in children. The major focus is on renal cellular and molecular events, with emphasis on those affecting the developing kidney. Recent Findings Experiments in the fetal sheep or neonatal rat, mouse, or ` ig reveal dramatic effects of urinary tract obstruction on renal growth and development. Surgical relief of obstruction reverse some af the structural and functional deficits, but can not restore normalcy. Renal tubular apoptosis is a major factor leading to tubular atrophy following unilateral ureteral obstruction. Increased reactive oxygen species, and a renal enivironment favoring pro-apoptotic, over survival, signals, contribute to cell death. A variety of intrarenal factors lead to progressive interstitial fibrosis, including the newly:described process of epithelialmeseriphymaktransilion, whereby tubular epithelial cells are transformed into activated fibroblasts. A number of endogenous ahtifibrotic-counter-regulatory molecules have been identified, opening the possibility of enhancing the kidney's own-defenses against progressive fibrosis. Summary The renal response to urinary tract obstruction is complex and involves a wide array of interacting molecules. Elucidation of these interactions will lead to the identification of biomarkers that will allow a more precise prediction to the response to surgical intervention and, hopefully, to novel therapies toprevent renal deterioration.