Effect of vasico-amniotic shunt for fetal obstructive uropathy in lambs

目的：梗阻性尿路病产前干预后儿童的长期结局令人失望。我们报道了在胎羊模型中梗阻后3周肾发育不良的变化。我们用这个模型来探讨胎儿intervention.Methods后的肾脏发育和膀胱功能：我们创建了一个梗阻性尿路病在胎羊在妊娠60天，通过结扎尿道和脐尿管。21天后进行膀胱造口术（雌性）或尿道造口术（雄性）。在足月（145天）处死胎儿，测量膀胱体积和顺应性。结果：22例胎儿均行尿道分流术。9人流产或死产。与对照组（71± 19 ml）相比，13例存活，11例成功分流，膀胱较小（8± 5 ml），p<0.05。分流膀胱顺应性差。组织学上，他们有增厚的粘膜下结缔组织与肥大的肌肉。肾组织的组织学表现出相对保存良好的肾结构，减少肾单位质量（少肾）在两只羔羊和多囊性发育不良变化（MCDK）在三个。六（55%）有正常的肾genes.Conclusions：在我们的模型中，分流手术后梗阻性尿路病不能保留膀胱功能。分流改善了囊性发育不良的发展，但一半的羔羊少肾或MCDK。这些人可能在以后的生活中发展为肾衰竭。

Purpose : The long term outcome for children after antenatal intervention for obstructive uropathies is disappointing. We reported that renal dysplastic changes are well established 3 weeks after obstruction in a fetal lamb model. We used this model to explore renal development and bladder function after fetal intervention.Methods: We created an obstructive uropathy in fetal lambs at 60 days gestation by ligating the urethra and urachus. A vesicostomy (female) or urethrostomy (male) were performed 21 days later. The fetuses were sacrificed at term(145 days) and bladder volume and compliance were measured. The urinary tract was processed for histological examination.Results: Twenty two fetuses were shunted. Nine miscarried or were still-born. Thirteen survived and eleven had a successful shunt with a small bladder (8±5ml) compared to controls (71±19ml), p<0.05. Shunted bladders had poor compliance. Histologically, they had thickened submucosal connective tissue with hypertrophied muscle. Histology of the renal tissue demonstrated relatively well-preserved renal architecture with reduced nephron mass (oligonephronia) in two lambs and multycystic dysplastic change (MCDK) in three. Six (55%) had normal nephrogenesis.Conclusions : In our model, shunt operations after obstructive uropathy fail to preserve bladder function. Shunting ameliorated the development of cystic dysplasia but half of the lambs had oligonephronia or MCDK. Thiese might develop renal failure later in life.