**5.1 Management of congenital upper urinary tract obstruction**

Regardless of the specific cause, unilateral upper urinary tract obstructive lesions rarely result in azotemia. Conservative management of these patients is often recommended, with surgery reserved for patients with clinical symptoms or declining renal function. However, over time up to 50% of patients with unilateral UPJ obstruction will meet these criteria and require surgical correction (Chertin et al., 2006). Additionally, some authors have raised concern about an increased long-term risk for hypertension as a result of ureteral obstruction, advocating for reconsideration of these conservative management approaches (Carlstrom, 2010). Relative to unilateral obstruction, bilateral upper tract obstruction or obstruction of a solitary functional kidney is far more ominous, and generally requires prompt surgical intervention and careful postsurgical management to minimize and monitor renal injury.

Congenital Obstructive Nephropathy: Clinical Perspectives and Animal Models 15

developed ESRD and 58% had normal renal function after a mean follow-up of 17.7 years. The authors of the latter study note that for the more severely affected patients, the functional outcome may be primarily determined by the severity of intrauterine obstruction and presence of renal dysplasia and not significantly altered by early diagnosis and treatment; however, for patients with more moderate disease, long-term prognosis may be improved by prenatal diagnosis and early interventions (Kousidis, et al., 2008). Other studies have not shown a statistically significant difference in outcomes between patients with renal dysplasia and those with normal-appearing kidneys (Nickavar, et al., 2008;

Antenatal intervention for suspected fetal obstructive nephropathy has been attempted by vesicoamniotic shunting, vesicocentesis, fetal cystoscopy, or open fetal bladder surgery. The results are variable and these methods remain controversial. A 2003 meta-analysis of the available data suggested improved perinatal survival following prenatal bladder drainage, particularly in cases with poor predicted prognoses (Clark et al., 2003). However, these procedures carry a high risk for complications including shunt malfunction or migration, urinary ascites, hemorrhage, chorioamnionitis, iatrogenic gastroschisis, premature labor, or miscarriage (Carr & Kim, 2010; Elder et al., 1987). The Percutaneous shunting in Low Urinary Tract Obstruction (PLUTO) study, a multicenter, prospective, randomized trial, was designed to systematically evaluate the prenatal and perinatal outcomes and risk/benefit ratio of *in utero* intervention for urological obstruction versus conservative management, and is currently in the data analysis phase (Kilby et al., 2007; Morris & Kilby, 2009;

In cases where renal function is affected or threatened, surgical relief of the obstruction or diversion of the urine path is necessary. Stents, catheters, or percutaneous drains may be useful to provide temporary drainage, but long-term management requires surgery. Discussion of the variety of surgical techniques and approaches that may be implemented in the management of congenital urinary obstructions is beyond the scope of this review.

Although such surgical interventions can relieve some of the effects of congenital impairment of urine flow, many developmental and pathologic changes associated with this condition appear irreversible. Many patients with congenital obstructive nephropathy, including the majority of patients with PUV, do not have complete recovery of kidney function following postnatal intervention (Parkhouse, et al., 1988; Reinberg, et al., 1992;

**5.5 Progressive chronic kidney disease in congenital obstructive nephropathy** 

Given the frequency of chronic and progressive renal impairment, the importance of longterm monitoring of all patients with congenital obstructive nephropathy cannot be overemphasized. Serial measurements of renal function, periodic urinalysis, blood pressure checks, and monitoring of growth should be performed for all patients with a history of congenital urinary obstruction. Renal impairment, if detected, should be fully evaluated and

Ylinen et al., 2004).

**5.3 Antenatal intervention** 

University of Birmingham, 2011).

Roth, et al., 2001; Sanna-Cherchi, et al., 2009).

**5.4 Postnatal intervention** 

#### **5.2 Natural history of lower urinary tract obstruction**

Obstruction of the bladder outlet or urethra affects urologic and renal functions at all points proximal to the lesion. Extrarenal effects may also occur, primarily in the lungs due to associated oligohydramnios. The profound changes that can result are outlined in Figure 6.

Fig. 6. Cascade of physiological consequences associated with lower urinary tract obstruction.

As many as 70% of boys with PUV develop advanced chronic or end-stage kidney disease (CKD Stage 3-5; Parkhouse et al., 1988; Reinberg et al., 1992; Roth et al., 2001; Sanna-Cherchi, et al., 2009). Those with ultrasound findings at or before 24 weeks' gestation are significantly more likely to have a poor renal outcome than children with PUV detected later in pregnancy after a normal second trimester scan (Hutton, et al., 1994). Among patients with PUV who survive the perinatal period, bladder dysfunction and nadir serum creatinine greater than 1.0 mg/dl are independent risk factors for progression to end stage renal disease (Ansari, et al., 2010; DeFoor et al., 2008). Unilateral or bilateral VUR associated with PUV may also have a significant impact on kidney function (Heikkila et al., 2009).

Long-term follow-up studies decades after treatment for PUV offer additional insight into the postnatal renal progression of this condition. Holmdahl and colleagues (2005) assessed Swedish men who were treated for PUV between 1956 and 1970. Over the 30 to 40 years between initial intervention and this follow-up assessment, the prevalence of ESRD in this population increased from 8% to 21%, and only 37% of the cohort had apparently normal renal function as adults (Holmdahl & Sillen, 2005). Kousidis et al. (2008) found that in a British cohort of patients diagnosed prenatally between 1984 and 1996, 28% died or developed ESRD and 58% had normal renal function after a mean follow-up of 17.7 years. The authors of the latter study note that for the more severely affected patients, the functional outcome may be primarily determined by the severity of intrauterine obstruction and presence of renal dysplasia and not significantly altered by early diagnosis and treatment; however, for patients with more moderate disease, long-term prognosis may be improved by prenatal diagnosis and early interventions (Kousidis, et al., 2008). Other studies have not shown a statistically significant difference in outcomes between patients with renal dysplasia and those with normal-appearing kidneys (Nickavar, et al., 2008; Ylinen et al., 2004).
