Chronic partial ureteral obstruction and the developing kidney.
Although congenital urinary tract obstruction is a common disorder, its pathophysiology remains poorly understood and clinical practice is controversial. Animal models have been used to elucidate the mechanisms responsible for obstructive nephropathy, and the models reveal that renal growth and function are impaired in proportion to the severity and duration of obstruction. Ureteral obstruction in the neonatal rat or mouse leads to activation of the renin-angiotensin system, renal infiltration by macrophages, and tubular apoptosis. Nephrons are lost by glomerular sclerosis and the formation of atubular glomeruli, and progressive injury leads to tubular atrophy and interstitial fibrosis. Recovery following release of obstruction depends on the timing, severity, and duration of obstruction. Growth factors and cytokines are produced by the hydronephrotic kidney, including MCP-1 and TGF-beta1, which are excreted in urine and can serve as biomarkers of renal injury. Because MRI can be used to monitor renal morphology, blood flow, and filtration rate, its use might supplant current imaging modalities (ultrasonography and diuretic renography), which have significant drawbacks. Combined use of MRI and new urinary biomarkers should improve our understanding of human congenital obstructive nephropathy and should lead to new approaches to evaluation and management of this challenging group of patients.
Chevalier
Robert L
RL
Department of Pediatrics, University of Virginia, Box 800386, Charlottesville, VA 22908, USA. RLC2M@virginia.edu
D000818:Animals; D015415:Biomarkers / Q000652:urine; D002908:Chronic Disease; D004195:Disease Models, Animal; D006801:Humans; D007668:Kidney / Q000254:growth & development*; D008279:Magnetic Resonance Imaging / Q000379:methods; D009393:Nephritis / Q000209:etiology; D014517:Ureteral Obstruction / Q000151:congenital* / Q000503:physiopathology / Q000628:therapy
D015415:Biomarkers