Elucidation of mechanism of MCDK and optimal treatment of obstructive uropathy in the Fetal Lamb

目的：目前尚不清楚尿路梗阻如何改变正常的肾脏形成并导致肾脏发育不良。我们在胎儿羔羊中创建了一个梗阻性尿病模型，并回顾了梗阻性肾脏的病理，以确定梗阻性减压的最佳时机。方法：采用结扎尿道、尿路的方法，对妊娠60天的胎羊羔进行梗阻性尿路病变治疗。他们在20-31天后通过剖腹产分娩。肾行组织学检查。结果：共手术60天羔羊34只。25例胎儿发育不良，24例胎儿肾源区有囊肿。多囊性发育不良肾（MCDK）的囊性成分主要位于近端小管。结论：子宫内尿路梗阻导致功能肾单位数量减少，并在肾源区和更深皮层产生囊肿。这些囊肿和扩张的近端肾小管抑制新肾元的形成。梗阻后20天有早期发育不良的特征，但肾源区仍然存在。我们认为早期分流术可以挽救肾功能。

Purpose : It is still unclear how urinary tract obstruction alters normal nephrogenesis ad leads to renal dysplasia. We created an obstructive uropathy model in fetal lambs ad reviewed the pathology of the obstructed kidney to determine the optimal timing for decompression of the obstruction.Methods : A obstructive uropathy was created in fetal lambs at 60 days gestation by ligating the urethra and urachus. They were delivered 20-31 days later by caesarian section. The kidneys were processed for histological examination.Results : Thirty four 60-day lambs were operated upon. Dysplastic changes were noted in 25 fetuses and 24 fetuses had cysts in the nephrogenic zone. The cystic components in multicystic dysplastic kidneys (MCDK) are mainly in the proximal tubules. Conclusions : In utero urinary tract obstruction causes reduction of numbers of functioning nephrons and produces cysts in the nephrogenic zone, and in the deeper cortex. These cysts and dilated proximal tubules suppress new nephron formation. Twenty days after obstruction there were early features of dysplasia but the nephrogenic zones were still present. We conclude that early shunting may salvage renal function.