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 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 x min(-1) x 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) micromol/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.
Edouga
D
D
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.
Hugueny
B
B
Gasser
B
B
Bussières
L
L
Laborde
K
K
D000818:Animals; D003404:Creatinine / Q000097:blood; D004268:DNA-Binding Proteins / Q000032:analysis; D004322:Drainage; D005312:Fetal Blood; D005315:Fetal Diseases / Q000097:blood / Q000503:physiopathology / Q000628:therapy*; D020567:Fetal Weight; D005865:Gestational Age; D007150:Immunohistochemistry; D007668:Kidney / Q000196:embryology* / Q000378:metabolism / Q000473:pathology; D007678:Kidney Glomerulus / Q000196:embryology; D051762:PAX2 Transcription Factor; D012756:Sheep; D014157:Transcription Factors / Q000032:analysis; D014524:Urethral Obstruction / Q000196:embryology / Q000503:physiopathology / Q000628:therapy*
D004268:DNA-Binding Proteins; D051762:PAX2 Transcription Factor; D014157:Transcription Factors; D003404:Creatinine