Edouga D, Hugueny B, Gasser B, Bussières L, Laborde K
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.
Am J Physiol Renal Physiol. 2001 Jul;281(1):F26-37. doi: 10.1152/ajprenal.2001.281.1.F26.
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.
在胎羊实验模型中研究了梗阻[尿路梗阻（UTO）]及其解除对肾脏发育的影响。在妊娠60天时进行膀胱出口梗阻；在妊娠90天时通过膀胱羊膜分流术解除梗阻。在妊娠120天时对梗阻胎儿（OF60；n = 11）、分流胎儿（SF；n = 5）和对照胎儿（CF；n = 11）进行研究。胎儿UTO可导致肾积水（64%）或发育异常（36%）；发育异常总是与肾小球数量减少有关[950±99（发育异常）对1,852±249（CF）个肾小球/切片]。梗阻胎儿的肌酐清除率较低[0.76±0.41（OF60）对0.96±0.21（CF）ml·min⁻¹·kg⁻¹]，钠排泄分数较高[17.2±20.3（OF60）对2.4±3.7%（CF）]，尿浓缩程度较高[80±30（OF60）对43±22（CF）μmol/l]。与未分流胎儿（1,379±502个肾小球/切片）相比，SF在妊娠120天时肾小球数量增加（1,643±106个肾小球/切片），梗阻后被破坏的PAX2时间模式得以恢复。总之，早期胎儿UTO可导致肾小球发育正常的肾积水或肾小球数量减少的发育异常；在肾发生结束前进行宫内尿液分流可能使观察到的肾小球发生停滞得到逆转。
