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Arrested development of the neonatal kidney following chronic ureteral obstruction
1Department of Urology, Gyeong-sang National University, Chinju, Korea.
Purpose:
The purpose of this study was to investigate the role of growth-related peptides in the impairment of renal growth and development resulting from unilateral ureteral obstruction (UUO) in the neonatal rats.
Materials And Methods:
Sprague-Dawley rats underwent UUO or sham-operation in the first 48-hours of life, and kidneys were harvested 1 to 28 days later. Renal messenger RNA (mRNA) was quantitated for renin, transforming growth factor-beta 1 (TGF-beta 1) and epidermal growth factor (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:
The normal developmental increase in renal mass and DNA content were suppressed in ipsilateral UUO and increased in the intact opposite kidney. Renal interstitial volume was increased more than 10-fold by ipsilateral UUO. Unilateral ureteral obstruction resulted in a sustained increased in ipsilateral renal renin mRNA and persistence of fetal renin distribution. Renin in the contralateral kidney was suppressed. Transforming growth factor-beta 1 expression increased progressively in the obstructed 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 maturation. However, EGF expression remained suppressed in the obstructed kidney. 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-related peptides, neonatal UUO delays ipsilateral renal development, which may contribute to impaired renal growth.