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

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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.