**3.3 Functional obstruction**

Functional urological obstructions are conditions that result in impaired antegrade urine flow without evidence of a physical blockage. In many patients, the situation may be transient and can ultimately resolve without intervention, in which case a specific etiology may never be identified. In other cases a functional obstruction may result from myogenic or neurogenic causes, which can result in lifelong voiding dysfunction as well as significant renal impairment. Examples include conditions such as congenital neurogenic bladder (Ewalt & Bauer, 1996), congenital non-neurogenic neurogenic bladder (Vidal et al., 2009), and prune belly syndrome (Woodhouse et al., 1982).

### **3.4 Multisystem conditions associated with obstruction or voiding dysfunction**

#### **3.4.1 Prune belly syndrome**

Prune belly syndrome (Figure 5), also known as Eagle-Barrett syndrome, consists of the triad of underdeveloped abdominal wall musculature, urinary tract dilatation, and undescended testicles (Eagle & Barrett, 1950). Postnatally, urinary obstruction in prune belly syndrome is often functional rather than anatomic in nature. Prune belly syndrome has an incidence of 3.8 per 100,000 male births (Routh et al., 2010). The condition also occurs rarely in females, albeit necessarily lacking cryptorchidism (Reinberg, et al., 1991). Secondary VUR is present in 85% of patients with prune belly syndrome, and associated anomalies of the gastrointestinal, pulmonary, skeletal, and/or cardiac systems are common (Strand, 2004).

Two major theories, which are not mutually exclusive, have been advocated regarding the development of prune belly syndrome. One proposes that the condition arises from a fundamental flaw in mesoderm development (Straub & Spranger, 1981), while the other suggests that prune belly syndrome originates from a severe fetal urethral obstruction that results in massive distention of the bladder, degeneration of the abdominal wall musculature, and interruption of testicular descent (Pagon et al., 1979).

common, although not universal, in surviving patients with urethral atresia (Gonzalez, et

Large ureteroceles can prolapse through the urethra, which may result in bladder outlet obstruction. This is most frequently an acquired condition, although rarely prolapse may occur *in utero*, leading to features of congenital obstructive nephropathy (Sozubir et al.,

Urethral diverticula and anterior urethral valves are rare causes of infravesicular obstruction. Interestingly, although bladder pathology and variable degrees of hydroureteronephrosis result, renal function is usually not impaired after surgical correction

Functional urological obstructions are conditions that result in impaired antegrade urine flow without evidence of a physical blockage. In many patients, the situation may be transient and can ultimately resolve without intervention, in which case a specific etiology may never be identified. In other cases a functional obstruction may result from myogenic or neurogenic causes, which can result in lifelong voiding dysfunction as well as significant renal impairment. Examples include conditions such as congenital neurogenic bladder (Ewalt & Bauer, 1996), congenital non-neurogenic neurogenic bladder (Vidal et al., 2009),

**3.4 Multisystem conditions associated with obstruction or voiding dysfunction** 

Prune belly syndrome (Figure 5), also known as Eagle-Barrett syndrome, consists of the triad of underdeveloped abdominal wall musculature, urinary tract dilatation, and undescended testicles (Eagle & Barrett, 1950). Postnatally, urinary obstruction in prune belly syndrome is often functional rather than anatomic in nature. Prune belly syndrome has an incidence of 3.8 per 100,000 male births (Routh et al., 2010). The condition also occurs rarely in females, albeit necessarily lacking cryptorchidism (Reinberg, et al., 1991). Secondary VUR is present in 85% of patients with prune belly syndrome, and associated anomalies of the gastrointestinal, pulmonary, skeletal, and/or cardiac systems are

Two major theories, which are not mutually exclusive, have been advocated regarding the development of prune belly syndrome. One proposes that the condition arises from a fundamental flaw in mesoderm development (Straub & Spranger, 1981), while the other suggests that prune belly syndrome originates from a severe fetal urethral obstruction that results in massive distention of the bladder, degeneration of the abdominal wall

musculature, and interruption of testicular descent (Pagon et al., 1979).

of the obstruction (Arena et al., 2009; Gupta & Srinivas, 2000; Rawat et al., 2009).

al., 2001).

2003).

**3.2.3 Prolapsing ureterocele** 

**3.2.4 Other urethral obstructions** 

**3.3 Functional obstruction** 

**3.4.1 Prune belly syndrome** 

common (Strand, 2004).

and prune belly syndrome (Woodhouse et al., 1982).

Fig. 5. Radiological findings associated with prune belly syndrome in a 2 day old male. **A - E.** Ultrasound of urinary bladder (A), right (B) and left (C) ureters, right (D) and left (E) kidneys. The bladder (BL) is decompressed but bladder wall thickness is normal. Tortuous dilated ureters (U, RU, LU) are observed bilaterally in the lower abdomen. The kidneys are dysplastic and amorphous in appearance, with cysts of varying sizes. There is no corticomedullary differentiation in either kidney. **F.** VCUG. The protuberant abdomen resulting from lack of abdominal wall musculature is evident from the position of bowel loops (arrows) on this lateral view. This patient has an unusual configuration of the bladder, bladder base and posterior urethra. There is absence of the normal prostate and a very distended posterior urethra (PU) connecting to a dysplastic-appearing bladder (BL). No evidence of true PUV was found on this or any subsequent investigations. Reflux is observed into the distended right ureter (RU) but not the left. **G.** VCUG from another patient 10 days postnatally shows a more typical trabeculated bladder with the characteristic tubular shape of the bladder base in prune belly syndrome.

Congenital Obstructive Nephropathy: Clinical Perspectives and Animal Models 13

Many attempts have been made to identify useful diagnostic and prognostic biomarkers for congenital obstructive nephropathy. These include gestational age at diagnosis (Hutton et al., 1994); the volume of amniotic fluid (Oliveira et al., 2000; Sarhan et al., 2008); the presence of megacystis (Oliveira, et al., 2000); the appearance of the renal parenchyma on prenatal ultrasound (Morris et al., 2009; Robyr, et al., 2005; Sarhan, et al., 2008); fetal urinary sodium, calcium, 2-microglobulin, and other urinary solutes and proteins (Decramer et al., 2008; Morris et al., 2007). Additionally, pilot studies show that urine proteome analysis can identify urodynamically significant UPJ obstruction in infants with hydronephrosis with a sensitivity of 83% and a specificity of 92%, although the test had poor diagnostic accuracy in patients older than 1 year of age (Drube et al., 2010). Although several of these markers and tests show promise as diagnostic or prognostic tools, no consensus yet exists as to the best

Prenatally, the volume of amniotic fluid as well as ultrasound appearance of the bladder, urethra, and kidneys are common discriminators of the plan of care. Analysis of fetal urine can provide additional information; fetal urinary sodium less than 100 mmol/L, chloride less than 90 mmol/L, osmolality less than 210 mOsm/L, and low levels of urinary protein indicate good renal function (Shokeir & Nijman, 2000). Postnatally and in patients who present outside the neonatal period, management decisions are most frequently reliant on ultrasonography findings and other imaging modalities, coupled with serial measurements of serum creatinine. Serum creatinine is a relatively late marker of renal injury whose elevation often signals irreversible kidney damage (Nickavar et al., 2008; Sarhan et al., 2010). Nonetheless, nadir serum creatinine level is a useful and reliable prognostic indicator in patients with congenital

obstructive nephropathy (Ansari et al., 2010; Bajpai et al., 2001; Warshaw et al., 1985).

The effects of fetal urinary tract obstruction on renal development, renal function, and urodynamics will be unique to each individual patient, and there may be significant clinical variability between patients thought to have similar obstructive lesions or processes. The clinical course is influenced by many factors; those intrinsic to each patient include the developmental stage at which the obstruction arises, the degree and duration of blockage, and its location. However, accurate tools to measure and determine the prognostic impact of

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

**4.3 Prospective diagnostic and prognostic biomarkers** 

panel of biomarkers to assess congenital obstructive nephropathy.

**5. Clinical course, management, and outcomes** 

these various factors in any individual case do not exist.

monitor renal injury.

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