The Fate of Nephrons in Congenital Obstructive Nephropathy: Adult Recovery is Limited by Nephron Number Despite Early Release of Obstruction.
OBJECTIVE
Urinary tract obstruction and reduced nephron number often occur together as a result of maldevelopment of the kidneys and the urinary tract. We determined the role of nephron number on adaptation of the remaining nephrons of mice subjected to neonatal partial unilateral ureteral obstruction followed through adulthood.


METHODS
Wild-type and Os/+ mice (the latter with 50% fewer nephrons) underwent sham operation or partial unilateral ureteral obstruction in the first 2 days of life. Additional mice underwent release of unilateral ureteral obstruction at 7 days. All kidneys were harvested at 3 weeks (weaning) or 6 weeks (adulthood). Glomerular number and area, glomerulotubular junction integrity, proximal tubular volume fraction and interstitial fibrosis were measured by histomorphometry.


RESULTS
In the obstructed kidney unilateral ureteral obstruction caused additional nephron loss in Os/+ but not in wild-type mice. Glomerular growth from 3 to 6 weeks was impaired by ipsilateral obstruction and not preserved by release in wild-type or Os/+ mice. Proximal tubular growth was impaired and interstitial collagen was increased by ipsilateral obstruction in all mice. These conditions were attenuated by release of unilateral ureteral obstruction in wild-type mice but were not restored in Os/+ mice. Unilateral ureteral obstruction increased interstitial collagen in the contralateral kidney while release of obstruction enhanced tubular growth and reduced interstitial collagen.


CONCLUSIONS
Unilateral ureteral obstruction in early postnatal development impairs adaptation to reduced nephron number and induces additional nephron loss despite release of obstruction. Premature and low birth weight infants with congenital obstructive nephropathy are likely at increased risk for progression of chronic kidney disease.
Department of Pediatrics, University of Virginia, Charlottesville, Virginia.
Maria
M
Sergio
Department of Pediatrics, University of Virginia, Charlottesville, Virginia.
Carolina I
CI
Galarreta
Department of Pediatrics, University of Virginia, Charlottesville, Virginia.
Barbara A
BA
Thornhill
Department of Pediatrics, University of Virginia, Charlottesville, Virginia.
Michael S
MS
Forbes
Department of Pediatrics, University of Virginia, Charlottesville, Virginia. Electronic address: RLC2M@virginia.edu.
Robert L
RL
Chevalier
D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D049109:Cell Proliferation; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D051379:Mice; D009399:Nephrons / Q000473:pathology*; D051437:Renal Insufficiency / Q000209:etiology* / Q000473:pathology; D014517:Ureteral Obstruction / Q000150:complications* / Q000151:congenital / Q000473:pathology
chronic; disease progression; growth and development; nephrons; renal insufficiency; ureteral obstruction