ARRESTED DEVELOPMENT OF THE NEONATAL KIDNEY FOLLOWING CHRONIC URETERAL OBSTRUCTION

Purpose: The purpose of this study was to investigate the role of grow th-related peptides in the impairment of renal growth and development resulting from unilateral ureteral obstruction (UUO) in the neonatal r at. Materials and Methods: Sprague-Dawley rats underwent UUO or sham-o peration in the first 48 hours of life, and kidneys were harvested 1 t o 28 days later. Renal messenger RNA (mRNA) was quantitated for renin, transforming growth factor-beta 1 (TGF-beta 1) and epidemal growth fa ctor (EGF). Renal interstitial volume was measured in Masson-trichrome -stained sections, and renin and alpha-smooth muscle actin (alpha-SM. actin) distribution were determined by immunocytochemistry. Results: T he normal developmental increase in renal mass and DNA content were su ppressed by ipsilateral UUO and increased in the intact opposite kidne y. Renal interstitial volume was increased more than 10-fold by ipsila teral UUO. Unilateral ureteral obstruction resulted in a sustained inc rease in ipsilateral renal renin mRNA and persistence of fetal renin d istribution. Renin in the contralateral kidney was suppressed. Transfo rming growth factor-beta 1 expression increased progressively in the o bstructed kidney, but decreased after 7 days in sham-operated kidneys. While renal EGF expression was undetectable in the normal sham kidney during the first 3 days of life, it increased steadily with maturatio n. However, EGF expression remained suppressed in the obstructed kidne y. Whereas alpha-SM actin disappeared from the interstitium of normal rat kidneys by 15 days of age, it persisted in the obstructed neonatal kidney. Conclusions: As revealed by changes in expression of growth-r elated peptides, neonatal UUO delays ipsilateral renal development, wh ich may contribute to impaired renal growth.