Congenital obstructive uropathy: its origin and contribution to end-stage renal disease in children

Most children with end-stage renal failure are born with abnormal kidneys, with fetal obstructive uropathy accounting for about half these cases. Posterior urethral valves (PUV) is overwhelmingly the most common, specific diagnosis, and is confined to boys. In general, the condition is sporadic, although familial cases have been reported, perhaps suggesting that genetic factors play a role in pathogenesis. PUV can present antenatally, detected on routine fetal ultrasonography, or postnatally, when it is associated with renal failure and bladder dysfunction. Advances in postnatal surgery and medical management have reduced the mortality in PUV, but it is uncertain whether antenatal diagnosis or treatment (eg, with vesicoamniotic shunts) improves long-term renal outcome. Other disorders associated with human fetal obstructive uropathy are urethral atresia, the prune belly syndrome, and multicystic dysplastic kidney. The nephropathy associated with fetal obstructive uropathy is renal dysplasia and comprises undifferentiated and metaplastic tissues. Several studies in animals and in humans suggest that fetal urine flow impairment causes deregulation of renal precursor cell turnover and expression of growth factor/survival and transcription factor genes. Furthermore, some of these morphologic and molecular changes can be ameliorated experimentally by fetal surgical decompression or administration of specific growth factors.