Impaired nephrogenesis in rats with congenital obstructive uropathy

Purpose: Alterations caused by renal obstruction in developing kidneys are of particular interest in basic research of congenital obstructive uropathy . In rats nephrogenesis mainly occurs 7 to 10 days postnatally. Therefore, surgically induced neonatal ureteral obstruction in rats has been suggested to be analogous to congenital obstruction in the fetus. An attempt less pr one to surgical artifacts and assessing even earlier developmental stages i s to monitor the development of obstructed kidneys in rats with congenital obstructive uropathy. Materials and Methods: Rats from an inbred strain with congenital renal obs truction in 70% of their littermates were observed. Morphologically, signif icant hydronephrosis was not detected before day 5 post partum and progress ed with age. Unilateral obstructed kidneys were compared with contralateral kidneys and kidneys from healthy control animals at ages of 1, 5, 10, 18 a nd 32 days. A total of 72 renal units were investigated. The renal messenge r RNA expression of renin and transforming growth factor-beta1 (TGF-beta1) was quantified by competitive quantitative reverse transcription polymerase chain reaction using a gene specific complementary RNA standard. Results: In controls the gene expression of renin decreased from day 1 to d ay 18 and remained stable. TGF-beta1 expression increased during the first 10 days and then decreased again. Renin expression of the obstructed kidney s was reduced (p <0.05) on day 1, increased to a maximum versus controls (p <0.01) on day 10 and decreased to an unchanged elevated level (p <0.01) on days 18 and 32. Renin expression of the contralateral kidneys showed no si gnificant alterations to control kidneys. Messenger RNA expression of TGF-< beta>1 of obstructed kidneys stayed decreased during the first 10 days (p < 0.05), then increased excessively on day 18 (p <0.01) and slightly decrease d on day 32. TGF-beta1 expression of the contralateral kidneys was parallel to controls on a slightly elevated level, increased on day 18 and returned to control level on day 32. Conclusions: Within the postpartum period of nephrogenesis gene expression of renin and TGF-beta1 was decreased in obstructed kidneys compared to cont rols. As the renin angiotensin system and TGF-beta1 have important function s in normal kidney development, these results suggest impaired nephrogenesi s of congenital obstructed kidneys even before the onset of morphological s igns of hydronephrosis. These features differ from surgical induced unilate ral ureteral obstruction at birth and promise new insights into the pathoph ysiology of congenital obstructive uropathy.