Optimal timing of prenatal treatment of obstructive uropathy in the fetal lamb

Purpose: It was still unclear how urinary tract obstruction alters normal nephrogenesis and leads to renal dysplasia. The authors created an obstructive uropathy model in fetal lambs and reviewed the pathology of the obstructed kidney to determine the optimal timing for decompression of the obstruction.Methods: Obstructive uropathy was created in fetal lambs at 60 days’ gestation by ligating the urethra and urachus. They were delivered 20 to 31 days later by cesarian section. The kidneys were processed for histologic examination.Results: Thirty-four 60-day lambs were operated on. 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 still were present. Early shunting may salvage renal function.