Release of partial ureteral obstruction (PUO) in the neonatal mouse prevents proximal tubular but not glomerular damage, which is aggravated by congenital nephron loss

CONGENITAL REDUCTION IN NUMBER OF NEPHRONS IMPAIRS PROXIMAL TUBULAR GROWTH IN THE CONTRALATERAL KIDNEY DURING PARTIAL UNILATERAL URETERAL OBSTRUCTION

PURPOSE To compare the response of the contralateral (CL) kidney during partial unilateral uretaral obstruction (PUO) and from obstruction/release (PUO/Rel) to sham-operated kidneys in both wild-type (WT) mice and mice with 50% reduction of nephron number (Os/+) MATERIAL AND METHODS C57/BL6 WT and mice with oligosyndactylism and 50% reduction of nephron number (Os/+), were subjected to sham operation or PUO in the first 2 days of life. Additional mice underwent release of obstruction at 7 days (PUO-Rel). All kidneys were harvested at 6 weeks (adulthood). Using histomorphometry, glomerular number and area were determined by PAS staining, and proximal tubular (PT) mass and injury to the glome…

The Fate of Nephrons in Congenital Obstructive Nephropathy: Adult Recovery is Limited by Nephron Number

Background: Pediatric chronic kidney disease (CKD) is most often due to congenital anomalies of the kidneys and urinary tract (CAKUT), and obstructive nephropathy is the leading cause. Progression to renal failure, however, is more likely to develop in adulthood than childhood (Wuhl, CJASN 8: 67–74, 2013). Frequently associated with CAKUT, reduced nephron number (NN) at birth is an independent risk factor for adult CKD. Methods: To determine the role of NN in progression of congenital obstructive nephropathy, wild-type (WT) and reduced NN mice (Os/+) were subjected to sham operation or partial unilateral ureteral obstruction (UUO) in the first 2 days of life (prior to completion of nephroge…

Congenital reduction in number of nephrons accelerates renal damage, and limits proximal tubular growth response to release of neonatal partial ureteral obstruction

Aim: to analyze the evolution of the response to persistent partial ureteral obstruction (PUO) and obstruction/release (PUO/Rel) in mice with 50% reduction in the number of nephrons from 21 days of age (time of weaning) to 42 days of age (adulthood). Methods: C57/BL6 wild-type (WT) and mice with oligosyndactylism and 50% reduction of nephron number (Os/+), were subjected to sham operation or PUO in the first 2 days of life. Additional mice underwent release of obstruction at 7 days (PUO-Rel). The study was performed in kidneys harvested at 21 and 42 days. Using histomorphometry, glomerular area (GA) was determined by PAS staining, and fractional proximal tubular (PT) mass and intact glomeru…