**4.3 Prospective diagnostic and prognostic biomarkers**

12 Novel Insights on Chronic Kidney Disease, Acute Kidney Injury and Polycystic Kidney Disease

Approximately 50% of children with myelomeningocele have detrusor-bladder sphincter dyssynergy, resulting in a functional bladder outlet obstruction and development of hydronephrosis (Anderson & Travers, 1993). These patients can develop the same complications as those with anatomical obstructions, including upper urinary tract dilatation, VUR, incomplete bladder emptying, recurrent urinary tract infections, and CKD

In developed countries, antenatal diagnosis of congenital urinary obstructions is often made in mid-gestation (at 18-20 weeks), when many pregnant women undergo a detailed prenatal ultrasound. Megacystis with or without oligohydramnios is the characteristic ultrasound finding of lower urinary tract obstruction, whereas hydronephrosis may signal upper or lower urinary tract obstruction. Hydronephrosis is the most commonly detected anomaly on prenatal ultrasound, found in as many as 4.5% of fetuses (Ismaili, et al., 2003). Prenatal hydronephrosis may result from non-obstructive processes such as primary VUR or physiologic dilatation as well as from obstruction. Differentiating obstruction from nonobstructive causes of congenital hydronephrosis is critical because the prognosis and management vary significantly among these conditions. Factors for consideration in assessing fetal hydronephrosis include gestational age; gender; whether the finding is unilateral or bilateral; the degree of dilatation; the ultrasonic appearance of the renal parenchyma, including presence/absence of a kidney, echogenicity, evidence of cysts or dysplasia, cortical thickness, and corticomedullary differentiation; the presence, volume, and structure of the bladder; any evidence of dilatation elsewhere in the urinary tract; the presence of other abnormalities of the urogenital system (such as duplication) or outside the urinary tract; amniotic fluid volume; and the progression of all findings over serial evaluations (Pates & Dashe, 2006). Several diagnostic algorithms have been proposed for the evaluation of patients with prenatally detected hydronephrosis (de Kort et al., 2008; Ismaili et al., 2005; Karnak et al., 2009; Riccabona et al., 2008; Shokeir & Nijman, 2000; Yiee &

In the neonate with a suspected urological obstruction, multiple modalities may be needed for full evaluation. Renal ultrasound and voiding cytourethrogram usually play important roles in postnatal assessment of these patients, and in some cases CT, MRI, diuretic

If not detected prenatally, congenital obstructive nephropathy may present in the neonate, infant, child, adolescent or adult with poor urine output, weak urine stream, abdominal distention, palpable abdominal or flank mass, pain, incontinence, urinary tract infection, hematuria, altered serum chemistries, or as an incidental finding on

renography, urodynamic studies, or cystoscopy may be useful.

**4. Diagnosis of congenital obstructive nephropathy** 

**3.4.2 Spina bifida** 

(van Gool et al., 2001).

**4.1 Prenatal ultrasound** 

Wilcox, 2008).

imaging studies.

**4.2 Postnatal diagnosis** 

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 panel of biomarkers to assess congenital obstructive nephropathy.

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).
