PURPOSE: Urinary tract obstruction and reduced nephron number often occur together as a result of maldevelopment of kidneys and urinary tract.
We wished to determine the role of nephron number on the adaptation of remaining nephrons of mice subjected to neonatal partial unilateral ureteral obstruction (UUO) and followed through adulthood.
MATERIALS AND METHODS: Wild-type (WT) and Os/+ mice (with 50% fewer nephrons) were subjected to sham operation or partial UUO in the first 2 days of life. Additional mice underwent release of UUO 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, UUO caused additional nephron loss in Os/+ but not WT mice. Glomerular growth from 3 to 6 weeks was impaired by ipsilateral UUO and was not preserved by release in WT or Os/+. Proximal tubular growth was impaired and interstitial collagen was increased by ipsilateral UUO in all mice. These were attenuated by release of UUO in WT mice, but were not restored in Os/+ mice. UUO increased interstitial collagen in the contralateral kidney; release of UUO enhanced tubular growth and reduced interstitial collagen.
CONCLUSIONS: We conclude that UUO 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.
Written by:
Sergio M, Galarreta CI, Thornhill BA, Forbes MS, Chevalier RL. Are you the author?
Department of Pediatrics, The University of Virginia, Charlottesville, VA, USA.
Reference: J Urol. 2015 Apr 22. pii: S0022-5347(15)03858-6.
doi: 10.1016/j.juro.2015.04.078
PubMed Abstract
PMID: 25912494