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Effects of ureteral obstruction on renal growth
1Department of Pediatrics, University of Virginia, School of Medicine, Charlottesville 22908, USA.
Insights
Congenital obstructive nephropathy, like unilateral ureteral obstruction (UUO), severely impairs kidney growth and development. This condition involves complex cellular changes affecting proliferation, apoptosis, and extracellular matrix deposition.
Area of Science:
- Nephrology
- Developmental Biology
- Pathology
Background:
- Congenital obstructive nephropathy arrests renal growth, with early obstruction causing more severe impairment.
- Unilateral ureteral obstruction (UUO) in young animals leads to significant ipsilateral kidney growth deficits and contralateral compensatory growth.
Purpose of the Study:
- To investigate the mechanisms by which UUO affects renal growth and development.
- To elucidate the cellular and molecular changes induced by urinary obstruction in the developing kidney.
Main Methods:
- Experimental studies involving unilateral ureteral obstruction (UUO) at different ages.
- Analysis of renal growth, nephron number, renin-angiotensin system activity, interstitial fibrosis, growth factor expression, apoptosis, and clusterin expression.
Main Results:
- UUO at younger ages causes more severe ipsilateral kidney growth impairment and greater contralateral compensatory growth.
- Obstruction leads to renal dysplasia, reduced nephron number, activated renin-angiotensin system, vasoconstriction, interstitial fibrosis, delayed maturation markers, increased apoptosis, and altered clusterin expression.
Conclusions:
- UUO profoundly impairs renal growth and development through complex interactions affecting cell proliferation, apoptosis, and extracellular matrix regulation.
- The findings highlight the critical role of early urinary tract patency for normal kidney development and function.
Abstract:
Renal insufficiency due to congenital obstructive nephropathy is a consequence of arrested or abnormal renal growth. A number of experimental studies have shown that the younger the age at the time of unilateral ureteral obstruction (UUO), the more severe the growth impairment of the ipsilateral kidney, and the greater the compensatory growth of the opposite kidney ("counterbalance"). Urinary obstruction in early fetal life results in renal dysplasia and a decrease in the number of functioning nephrons. The renin-angiotensin system is highly activated in early development, and UUO further increases this activity, resulting in vasoconstriction and glomerular contraction. Long-term UUO also causes progressive interstitial fibrosis, which presumably contributes to arrested growth of the kidney. This may result from excessive deposition of extracellular matrix stimulated by increased expression of transforming growth factor-beta 1. Neonatal UUO delays the expression of epidermal growth factor, and prolongs the expression of peritubular alpha smooth muscle actin, suggesting that renal maturation is delayed by UUO. Renal apoptosis is increased by UUO, which may contribute to the reduced DNA content of the neonatal obstructed kidney. Renal expression of clusterin, a glycoprotein associated with cell adhesion and protection from apoptosis, is increased by ipsilateral UUO, and also presumably modulates renal growth. Thus, renal growth and development are impaired by UUO through complex interactions between regulators of cell proliferation, cell destruction, and extracellular matrix.