Recovery after relief of fetal urinary obstruction: morphological, functional and molecular aspects

The effects of obstruction [urinary tract obstruction (UTO)] and relief on renal development were examined in an experimental model in the fetal lamb. Bladder outlet obstruction was performed at 60 days of gestation; relief w as performed by vesicoamniotic shunting at 90 days of gestation. Studies we re carried out in obstructed (OF60; n = 11), shunted (SF; n = 5), and contr ol fetuses (CF; n = 11) at 120 days of gestation. Fetal UTO produced either hydronephrosis (64%) or dysplasia (36%); dysplasia was always associated w ith a reduction in the number of glomeruli [950 +/- 99 (dysplasia) vs. 1,85 2 +/- 249 (CF) glomeruli/section]. Obstructed fetuses had lower creatinine clearance [0.76 +/- 0.41 (OF60) vs. 0.96 +/- 0.21 (CF) ml.min(-1).kg(-1)], higher sodium fractional excretion [17.2 +/- 20.3 (OF60) vs. 2.4 +/- 3.7% ( CF)], and higher urinary concentration [80 +/- 30 (OF60) vs. 43 +/- 22 (CF) mu mol/l] than controls. In SF, the number of glomeruli was increased at 1 20 days of gestation (1,643 +/- 106 glomeruli/section) compared with nondiv erted fetuses (1,379 +/- 502 glomeruli/section), and the temporal pattern o f PAX2, disrupted after obstruction, was restored. In conclusion, early fet al UTO leads to either renal hydronephrosis with normal glomerular developm ent or dysplasia with a decreased number of glomeruli; in utero urine diver sion performed before the end of nephrogenesis may allow a reversal of the glomerulogenesis arrest observed.