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

Abstract

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 was performed by vesicoamniotic shunting at 90 days of gestation. Studies were carried out in obstructed (OF60; n = 11), shunted (SF; n = 5), and control fetuses (CF; n= 11) at 120 days of gestation. Fetal UTO produced either hydronephrosis (64%) or dysplasia (36%); dysplasia was always associated with a reduction in the number of glomeruli [950 ± 99 (dysplasia) vs. 1,852 ± 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) μmol/l] than controls. In SF, the number of glomeruli was increased at 120 days of gestation (1,643 ± 106 glomeruli/section) compared with nondiverted fetuses (1,379 ± 502 glomeruli/section), and the temporal pattern of PAX2, disrupted after obstruction, was restored. In conclusion, early fetal UTO leads to either renal hydronephrosis with normal glomerular development or dysplasia with a decreased number of glomeruli; in utero urine diversion performed before the end of nephrogenesis may allow a reversal of the glomerulogenesis arrest observed.