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Department of Physiology, Necker-Enfants Malades Hospital, Institut National de la Santé et la Recherche Médicale Unité 356, Institut Fédératif de Recherche 58, Paris, France
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.
renal development; dysplasia; PAX2; urinary hyperpression
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