Hindawi Publishing Corporation International Journal of Nephrology Volume 2012, Article ID 351067, 4 pages doi:10.1155/2012/351067 Review Article Posterior Urethral Valves: Renal Failure and Prenatal Treatment Daniel P. Casella, Jeffrey J. Tomaszewski, and Michael C. Ost Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA Correspondence should be addressed to Jeﬀrey J. Tomaszewski, tomaszewskijj@upmc.edu Received 16 January 2011; Accepted 19 June 2011 Academic Editor: Pedro-Jose Lopez Egan˜a Copyright © 2012 Daniel P. Casella et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Posterior urethral valves occur in 1 : 5000 live births. Despite the high prevalence, the few children that survive do poorly, with over 50% progressing to ESRD in 10 years. The gold standard for post-natal diagnosis is voiding cystourethrography, while pre-natal diagnosis is dependent on routine screening ultrasonography. Despite the ability to identify features of bladder outlet obstruction early in fetal development, there is no consensus on how to incorporate early detection into current screening protocols. There has yet to be a marker that allows prediction of obstruction in the absence of or prior to radiographic evidence of obstruction. With our current screening strategy, the majority of interventions are performed well after irreversible damage has occurred. Improved mortality and long term morbidity from posterior urethral valves and congenital bladder outlet obstruction will likely remain unchanged until it is possible to intervene prior to the onset of irreversible renal damage. New biologic markers and improved instrumentation will allow for more eﬀective diagnosis and intervention at earlier stages of fetal development. 1. Introduction Posterior urethral valves occur in 1 : 5000 [1] live births and in approximately every 1/1250 fetal ultrasound screen- ings [2]. Despite the high prevalence, the most common treatment for valves identiﬁed in utero is fetal termination [3]. The few children that survive do poorly, with over 50% progressing to ESRD in 10 years [4]. Procedures for fetal bladder decompression were ﬁrst introduced over 25 years ago; however they still remain technically diﬃcult with limited proven beneﬁt [5]. Routine prenatal ultrasound is currently not recommended until 20 weeks of gestation [6]. New understanding of the pathogenesis of renal dysplasia and long-term renal dysfunction demonstrate that changes in renal development and architecture may begin to occur as early as 14 weeks of gestation (7, 13, 40). In animal models of complete outlet obstruction, renal damage is signiﬁcant and irreversible in as little as 30 days [7]. With our current screen- ing strategy, the majority of interventions are performed well after irreversible damage has occurred. Improved mortalility and long-term morbidity from posterior urethral valves and congenital bladder outlet obstruction will likely remain unchanged until it is possible to intervene prior to the onset of irreversible renal damage. 2. Embyologic Development The deﬁnitive kidney of a human embryo, the metanephros, begins development on the 28th day of gestation when the ureteral bud comes in contact with the metanephric mes- enchyme. Through reciprocal mesenchymal/epithelial inter- actions, the collecting system is formed from the branching urteric bud and the nephron from the overlying mesen- chyme. Fetal urine production begins as early as 8 weeks, and by 12 weeks, the collecting system including ureters and urinary bladder has formed. It is not until the 13th week that smooth muscle and autonomic innervation of the bladder are complete [8]. While further maturation of existing nephrons occurs after birth, nephrogenesis is completed by 34 weeks of gestation [9]. 3. Pathogenesis of Renal Dysfunction There is no single genetic mutation or biologic model that reproduces the phenotype of posterior urethral valves or con- genital bladder outlet obstruction. In early work with fetal sheep, surgical obstruction caused hydronephrosis within one week and resulted in dysplastic changes at term [10]. Further studies conﬁrmed the presence of dysplastic changes