Obstructive nephropathy: lessons from cystic kidney disease.
Obstructive nephropathy is one of the most important causes of renal failure in infants and children, while polycystic kidney disease (PKD) is a major cause of renal failure in the adult population. This review summarizes the evidence that there may be a number of mechanisms common to the pathophysiology of both conditions. In animal models of obstructive nephropathy and PKD, the renal tubular expression of epidermal growth factor is suppressed, and expression of clusterin is increased, both of which suggest arrested maturation or dedifferentiation of the tubular cell. There is a marked increase in apoptosis of epithelial cells in dilated tubules, associated with an increase in apoptotic stimuli. The renin-angiotensin system is activated in both obstructive nephropathy and PKD, which may contribute to tubular atrophy and interstitial fibrosis, which characterize the progression of both conditions. Focal cystic dilatation of the tubule is found in obstructive nephropathy, while tubular obstruction is present in cystic kidney disease. It is therefore likely that elucidation of the effects of mechanical stretch on renal tubular epithelial cells will contribute to our understanding of both conditions.
Chevalier
R L
RL
Department of Pediatrics, University of Virginia, School of Medicine, Charlottesville, VA, USA. rlc2m@virginia.edu
D000328:Adult; D000818:Animals; D017209:Apoptosis; D002675:Child, Preschool; D004815:Epidermal Growth Factor / Q000502:physiology; D006801:Humans; D007223:Infant; D007674:Kidney Diseases / Q000209:etiology*; D007684:Kidney Tubules / Q000473:pathology / Q000503:physiopathology; D007690:Polycystic Kidney Diseases / Q000209:etiology*; D012084:Renin-Angiotensin System / Q000502:physiology; D014517:Ureteral Obstruction / Q000150:complications
D004815:Epidermal Growth Factor