Variable chronic partial ureteral obstruction in the neonatal rat: A new model of ureteropelvic junction obstruction1

Abstract

Congenital ureteropelvic junction (UPJ) obstruction is a common developmental anomaly. To elucidate the mechanisms underlying the renal consequences of congenital UPJ obstruction, we have developed a new model of variable partial unilateral ureteral obstruction (UUO) in the neonatal rat. Rat pups were subjected to sham-operation, complete UUO, or variable partial UUO within the first day of life. After 14 or 28 days, the relative number of glomeruli, cell proliferation, tubular apoptosis, tubular atrophy, and interstitial fibrosis were quantitated in histologic sections. Glomerular filtration rate (GFR) was determined after 28 days of partial or complete UUO. Following 70% to 75% reduction in ureteral diameter, renal growth from 14 to 28 days was reduced by 60%, and the number of glomeruli decreased by 50%. Renal pelvic diameter increased in proportion to the severity of obstruction following 14 days of partial UUO, and by 28 days, was maximally dilated regardless of the luminal diameter. Renal proliferation was increased, while tubular apoptosis, tubular atrophy, and interstitial fibrosis were less severe 14 days following partial UUO than in complete UUO. GFR was reduced by 80%, and proteinuria developed following 28 days of partial UUO. Renal function is impaired by chronic ipsilateral partial UUO, which reduces the number of nephrons, and leads to progressive renal pelvic dilatation. Tubular atrophy and interstitial fibrosis develop prior to significant renal pelvic dilatation. Correlation of clinically measurable parameters with renal morphometry or imaging studies in this model may lead to new approaches to the management of congenital UPJ obstruction.