Pathogenesis of renal injury in obstructive uropathy.
OBJECTIVE
This 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.


RESULTS
Experiments in the fetal sheep or neonatal rat, mouse, or pig reveal dramatic effects of urinary tract obstruction on renal growth and development. Surgical relief of obstruction can reverse some of the structural and functional deficits, but cannot restore normalcy. Renal tubular apoptosis is a major factor leading to tubular atrophy following unilateral ureteral obstruction. Increased reactive oxygen species, and a renal environment 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 epithelial-mesenchymal transition, whereby tubular epithelial cells are transformed into activated fibroblasts. A number of endogenous antifibrotic counter-regulatory molecules have been identified, opening the possibility of enhancing the kidney's own defenses against progressive fibrosis.


CONCLUSIONS
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 to prevent renal deterioration.
Chevalier
Robert L
RL
Department of Pediatrics, University of Virginia, Charlottesville, Virginia 22908, USA. RLC2M@virginia.edu
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000502:physiology; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D055513:Connective Tissue Growth Factor; D064550:Death-Associated Protein Kinases; D018450:Disease Progression; D004815:Epidermal Growth Factor / Q000502:physiology; D006801:Humans; D017874:Immediate-Early Proteins / Q000502:physiology; D018836:Inflammation Mediators / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000502:physiology; D007668:Kidney / Q000503:physiopathology; D007674:Kidney Diseases / Q000503:physiopathology*; D007684:Kidney Tubules / Q000503:physiopathology; D014517:Ureteral Obstruction / Q000503:physiopathology*
D051017:Apoptosis Regulatory Proteins; C526317:CCN2 protein, human; C526318:CCN2 protein, mouse; C526316:CCN2 protein, rat; D017874:Immediate-Early Proteins; D018836:Inflammation Mediators; D036341:Intercellular Signaling Peptides and Proteins; D055513:Connective Tissue Growth Factor; D004815:Epidermal Growth Factor; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases