Early release of neonatal ureteral obstruction preserves renal function

Abstract

The incidence of congenital hydronephrosis is ∼1% and is often associated with renal insufficiency. It is unknown whether early release is essential to prevent deterioration of renal function. Rats were subjected to partial unilateral ureteral obstruction (PUUO) on postnatal day 2. The obstruction was left in place or released after 1 or 4 wk. Renal blood flow (RBF) and kidney size were measured sequentially over 24 wk using MRI. In rats in which the obstruction was left in place, RBF of the obstructed kidney was progressively reduced to 0.92 ± 0.17 vs. 1.79 ± 0.12 ml·min−1·100 g body wt−1( P < 0.05) after 24 wk. Similarly, glomerular filtration rate of the obstructed kidney was severely reduced at 24 wk: 172 ± 36 vs. 306 ± 42 μl·min−1·100 g body wt−1( P < 0.05). These changes were preceded by development of severe hydronephrosis and obstructive nephropathy with a reduction in total protein content: 45 ± 3 vs. 58 ± 4 mg/kidney. Moreover, nonreleased PUUO caused a marked natriuresis (0.32 ± 0.07 vs. 0.11 ± 0.02 μmol·min−1·100 g body wt−1, P < 0.05) and impaired solute free water reabsorption (0.47 ± 0.16 vs. 2.71 ± 0.67 μl·min−1·100 g body wt−1, P < 0.05), consistent with a significant downregulation of Na-K-ATPase to 62 ± 7%, aquaporin-1 to 53 ± 3%, and aquaporin-3 to 53 ± 7% of sham levels. Release after 1 wk completely prevented development of hydronephrosis, reduction in RBF and glomerular filtration rate, and downregulation of renal transport proteins, whereas release after 4 wk had no effect. These results suggest that early release of neonatal obstruction provides dramatically better protection of renal function than release of obstruction after the maturation process is completed.