2 and altered nephrogenesis in kidney’s exposed to outlet ob- struction during development [11–13]. Altered cellular dif- ferentiation, phenotypic changes in glomerular cells [14], apopotosis, and increased oxidative stress [15] contribute to decreased nephrogenesis and renal dysplasia. A key early event appears to be distention and mechanical stretch of the dilated collecting system, leading to activation of the apop- totic and inﬂammatory cascades [16]. The decreased number of total nephrons present at birth leads to hyperﬁltration injury, exacerbation of the underlying inﬂammatory process, renal ﬁbrosis, and ultimately renal failure [17, 18]. The early impact of altered diﬀerentiation and activation of the apoptotic cascade clearly illustrates that the molecular mechanisms and alterations in renal architec- ture which underlie progressive renal failure are established in utero. 4. Pathophysiology of Posterior Urethral Valves Posterior urethral valve (PUV) is the most common cause of obstructive uropathy leading to renal failure in male neonates [19]. Although the true incidence of PUVs is not precisely known, PUV is estimated to occur in 1 : 5000 live births [1]. The normal male urethra is anatomically divided into the prostatic and membranous portions (posterior urethra) and the spongy or anterior urethra. The urethral crest is a mucosal ridge that gives a speciﬁc form to the posterior urethra, and on either side of the ridge is the prostatic sinus. The urethral crest continues below the verumontanum and coalesces in a small midline bridge. This membrane, extending laterally and downward, eventually vanishes [20]. The classic form of PUV is found in the prostatic urethra, below or proximal to the verumontanum. Although the precise embryologic mechanism of PUV remains unknown [21], four theories have been proposed to explain their devel- opment and include hypertrophy of the urethral mucos- al folds, persistence and continuation of the urogenital mem- brane [22], abnormal development of the Wolﬃan or Mulle- rian duct [23], and fusion of the verumontanum or the pos- terior urethral roof epithelium [24]. 5. Diagnosis 5.1. Radiographic Diagnosis. The gold standard for post- natal diagnosis is voiding cystourethrography, while pre- natal diagnosis is dependent on routine screening ultra- sonography. According to ACOG guidelines, the optimal time to perform an ultrasound examination, in the absence of a speciﬁc indication for 1st trimester screening, is be- tween 18 and 20 weeks [6]. Studies from the early 1990s revealed that the classic ﬁndings of bilateral hydronephrosis, distended bladder, dilated posterior urethra, and thickened bladder wall are missed in the majority of cases if screening ultrasound is performed prior to 24 weeks [25–28]. With the signiﬁcant improvement in ultrasound over the past decade, it is our hope that the ability to detect PUV prior to 24 weeks has improved; however there are no contemporary series addressing this question. Between 18 and 22 weeks, 2–5% of fetuses will be found to have dilation of the renal International Journal of Nephrology pelvis. Hydronephrosis detected during the 2nd trimester resolves by term in over 80% of cases, while 40% of infants requiring surgery for urinary obstruction have no evidence of hydronephrosis on prenatal ultrasound. Megacystis, a potential early marker of bladder outlet obstruction, can now be identiﬁed as early as 11–14 weeks of gestation [29]. 75% of fetuses with megacystis (from 7–15 mm) will have a normal karyotype and 90% will spontaneously resolve, while the remaining 10% will progress to obstructive uropathy. There have also been reports of megacystis diagnosed at 11 weeks progressing to the development of new bilateral hydronephrosis by 13 weeks [30, 31]. Megacystis may be an early ﬁnding in outlet obstruction and the hydronephrosis associated with outlet obstruction may be identiﬁable earlier than previously thought. Despite the ability to identify features of bladder outlet obstruction early in fetal devel- opment, there is no consensus on how to incorporate early detection into current screening protocols. 5.2. Biochemical Diagnosis. Fetal urinary electrolytes are the only biological markers that have been studied as an in utero indicator of renal function and predictor of long- term function. Despite extensive reporting in the literature and widespread utilization of fetal urinary electrolytes, a recent meta-analysis demonstrated no signiﬁcant predictive value of urinary electrolytes in the diagnosis of obstructive uropathy or long-term renal preservation [32]. Studies aimed at classifying hydronephrosis have also attempted to identify biological markers of functionally signiﬁcant obstruction. Given the new and more extensive understanding of inﬂam- mation’s role in the etiology of renal damage, it is not surprising that TGF-β1, TNF-alpha, and MCP-1 have all been found to be elevated in children with UPJ obstruction [33, 34]. Proteomic analysis of children with UPJ obstruction identiﬁed several collagen degradation products predictive of renal obstruction severity [35]. To date, none of these markers have been studied in the fetal environment or prior to the radiologic diagnosis of obstruction. There has yet to be a marker that allows prediction of obstruction in the absence of or prior to radiographic evidence of obstruction. 6. Treatment The most common therapy for antenatal bladder outlet obstruction remains pregnancy termination [3]. Early ther- apies to relieve fetal urinary obstruction were performed through open fetal ureterostomies and cutaneous vesicos- tomies [36]. Given the risks of open fetal surgery, a minimally invasive percutaneous approach was adopted. In what has now become the most common approach, a trocar is placed into the fetal bladder through which a double-j catheter is positioned allowing drainage of fetal urine into the amniotic ﬂuid cavity. Percutaneous stent placement was widely used initially; however reviews 5 years after its implementation reported a 4.6% fetal mortalilty rate and a complication rate of 44% [37]. Reports of high complication rates coupled with poor fetal long-term survival led to decreased utilization of percutaneous drainage, and its use remains experimental. In a more contemporary series, when placed between 20 and