Diagnosis and management of prenatal urinary tract dilatation

Definitions and scope of prenatal urinary tract dilation

Abnormal dilation of the fetal urinary tract is a common finding during antenatal screening ultrasound (US) (1%–3% of all pregnancies), second only to cardiac defects. This dilation signifies a spectrum of disease, in some children a transient and physiologic phenomenon and in others an association with significant renal functional impairment. Table 11.1 lists common and impactful causes of prenatal urinary tract dilation (UTD) with their relative incidences. The term “prenatal urinary tract dilation” encompasses a number of commonly used radiographic terms including but not limited to hydronephrosis, pelviectasis, pyelectasis, and pelvicaliectasis, and it does not infer any pathophysiology underlying the imaging finding. Despite being such a common diagnosis, there is significant variability in the evaluation and management of UTD in the fetus and the neonate. With recent creation of a common nomenclature for UTD and increasing prospective research focused on UTD outcomes, UTD management has increasingly been refined.

Both health care providers caring for women with high-risk pregnancies and those caring for the children affected by these abnormalities should be familiar with the effects of UTD on the developing kidney, antenatal management of UTD, its effects on postnatal outcomes, and evidenced-based management strategies.

Antenatal diagnosis of urinary tract dilation

Maternal fetal ultrasound

The kidneys and bladder can consistently be detected on prenatal US by the end of the first trimester. The most severe urinary tract abnormalities are likely to appear on the first screening US, which in the United States is recommended between 18 and 22 weeks’ gestational age. Ultrasonography has a high sensitivity for UTD, with large studies reporting a sensitivity up to 92%. Abnormalities detected on screening US often prompt referral to a specialized high-risk obstetrics practice able to perform a comprehensive US to confirm the abnormality as well as screen other organ systems.

The measurement of anterior-posterior renal pelvis diameter (APD) has traditionally been the most commonly used dimension to communicate severity of UTD on prenatal US ( Fig. 11.1 ). The established normal value for APD prior to 28 weeks’ gestation is ≤4 mm and ≤7 mm after 28 weeks’ gestation. Notably, this system of classification is highly specific for obstruction in patients with severe dilation, and studies have identified 15 mm of APD detected in the third trimester as a threshold predictive of ureteropelvic junction (UPJ) obstruction. ^, The APD system, however, does not address other important elements of UTD including ureteral and bladder abnormalities or the impact of oligohydramnios.

In 2014, a multispecialty consensus meeting including representatives from eight professional societies involved in the diagnosis and management of UTD was held to unify grading systems and establish a common language among practitioners. The goals were to develop a standard process for imaging and reporting of US results both antenatally and postnatally. The Urinary Tract Dilation (UTD) Grading System was chosen to describe all degrees of antenatal and postnatal dilation, attempting to limit terms such as hydronephrosis and pelviectasis. This system has both objective and subjective components and measures APD, central calyceal dilation, peripheral calyceal dilation, appearance and thickness of kidney parenchyma, appearance of ureters, appearance of bladder, and unexplained oligohydramnios ( Table 11.2 ).

TABLE 11.2

Prenatal and Postnatal Parameters for Detection of Urinary Tract Dilation for the Urinary Tract Dilation Grading System

Ultrasound Parameter	Measurement/Findings	Notes
Anterior posterior renal pelvis diameter	Millimeters (mm)	Measured on transverse image at maximum diameter of renal pelvis; measured with spine in 6 o’clock or 12 o’clock position
		Normal ranges by age: Prenatal <28 weeks: <4 mm Prenatal ≥28 weeks: <7 mm Postnatal: <10 mm
Calyceal dilation
Central (major calyces)	Present/absent	Subjective assessment
Peripheral (minor calyces)	Present/absent	Subjective assessment
Parenchymal thickness	Normal/abnormal	Subjective assessment
Parenchymal appearance	Normal/abnormal	Evaluation of echogenicity and corticomedullary differentiation and for cortical cysts
Ureter	Normal/abnormal	Visualization considered dilated and abnormal, though intermittent visualization of the ureter considered normal postnatally
Bladder	Normal/abnormal	Evaluation of bladder wall thickness, presence of ureterocele, dilated posterior urethra
Unexplained oligohydramnios	Present/absent

Using the UTD Grading System, fetuses are classified into a low-risk group (UTD A1, denoted “A” for “antenatal”) or an increased risk group (UTD A2–3) ( Fig. 11.2 ). Since its inception, multiple studies have examined the correlation between UTD grade and clinical outcomes. These studies have demonstrated a grade-dependent correlation between fetal UTD and postnatal urological abnormalities; higher grades were shown to correlate with lower risk of spontaneous resolution, longer time to resolution, higher risk of urinary tract infections (UTIs), decreased ipsilateral renal function on renal scintigraphy (RS), and higher risk for need for surgical intervention. A caveat to the UTD Grading System is that it does not specifically refer to those children in whom bladder outlet obstruction is suspected. These children require expedited evaluation and a different management algorithm.

Historically, when a diagnosis of antenatal UTD is made, there has been lack of consensus regarding the frequency and timing of antenatal and postnatal follow-up imaging. A 2006 metaanalysis by Lee et al. found large variability among protocols. Recommendations ranged from vague (e.g., “serially as needed”) to specific (e.g., “once at 32–34 weeks”) and from infrequent (e.g., “once in the third trimester”) to numerous (e.g., “once per month”). Contemporary recommendations for ongoing antenatal management continue to be refined based on prospective research and attempts to minimize unnecessary studies ( Fig. 11.3 ).

Effects of urinary tract dilation on the fetal kidney

The impact of UTD on the fetal kidney ultimately depends on the pathophysiology causing the UTD. It is believed that transient UTD, or UTD that spontaneously resolves prenatally or postnatally with no clinical sequelae, is physiologic and nonpathologic to the developing kidney.

Although the exact pathophysiology of renal maldevelopment associated with vesicoureteral reflux (VUR), or “reflux nephropathy,” is not completely understood, it can in part be explained by the theory of Mackie and Stephens that an abnormal origin of the ureteric bud will interact abnormally with the metanephric blastema. Studies have confirmed the association of VUR with a small kidney, reduction in ipsilateral relative renal function, and focal and global areas of poor radiotracer uptake on RS.

Obstructive uropathy significantly disrupts normal kidney development, and the effects of obstruction on kidney formation and growth have been well studied. Normal kidney development consists of the acquisition and development of new nephrons (nephrogenesis), the enlargement and growth of existing kidney structures (morphogenesis), and differentiation of the specific functions of the parts of the kidney (segment-specific differentiation). Obstruction is thought to effect all of these processes. Indeed, significant obstructive uropathy results in renal hypodysplasia with a decrease in healthy parenchyma, disrupted architecture often with reduced formation of the medulla, a reduction in the number of glomeruli, cystic transformation of the glomeruli and tubules along the full length of the nephron, remodeling of the developing collecting ducts, and marked expansion and fibrosis of the kidney interstitium. Dysplasia is considered irreversible. The small, obstructed kidney is not considered atrophic but hypoplastic, as the obstructed kidney may demonstrate impaired or accelerated growth. The critical factor leading to dysplasia in animal studies has been a complete obstruction early in gestation. Obstructive conditions have been shown to alter expression of growth-regulatory genes and the presence of proteins coded by these genes. Additionally, the role of inappropriate apoptosis in congenital obstruction has become more firmly established in recent years.

The precise effects of obstructive uropathy on fetal kidney function have largely been extrapolated from animal models and from infants born with urinary tract obstruction. There is experimental evidence that obstruction leads to a deficit in nephrons and reduction in fetal glomerular filtration rate (GFR). ^, In both human and nonhuman primate fetuses, obstruction causes collecting duct and tubular injury. With obstruction, there is collecting duct epithelial remodeling noted early in fetal development and a reduction in intercalated cells seen by late gestation. ^, Proximal tubule epithelial cell injury has been reported in developing rat kidneys. These functional abnormalities are difficult to quantify in the fetus, but in newborns affected by severe posterior urethral valve (PUV), a decrease in GFR, tubular abnormalities leading to a defect in concentrating ability and thus polyuria, urinary salt wasting due to a decrease in tubular sodium reabsorption, and metabolic acidosis due to altered cell expression for collecting duct intercalated cells have all been recognized.

Radiographic findings on prenatal ultrasonography such as hyperechoic renal parenchyma, poor corticomedullary differentiation, and cystic changes can signify renal dysplasia; however, prenatal radiographic changes are an imperfect measurement of renal function. Amniotic fluid volume can act as a surrogate measure for fetal GFR, as the fetal kidneys become the main source of amniotic fluid production by 20 weeks’ gestation. Any impairment of fetal kidney function, including obstructive uropathies, can manifest as oligohydramnios from the second half of pregnancy onward. Fetal blood levels of β ₂ -microglobulin, the light chain of the class I major histocompatibility complex antigens, have also been used to estimate fetal GFR. Levels are higher in fetuses with urinary tract obstruction, reflecting a decrease in its clearance due to kidney injury. More commonly, fetal urine electrolytes are used to measure fetal kidney function, especially in suspected bladder outlet obstruction. Tubular reabsorption of electrolytes is hypothesized to be impaired, resulting in high fetal urinary sodium and chloride concentrations. Fetal electrolyte levels have been associated with postnatal kidney function ^, ; however, there is not one clear analyte or threshold level that accurately predicts postnatal kidney function.

Prediction of postnatal outcome

Before the advent of antenatal US and diagnosis of UTD, postnatal UTD presentation could range from asymptomatic with diagnosis later in life, symptomatic disease during childhood or adulthood with bladder dysfunction, recurrent UTIs, pyelonephritis or varying degrees of chronic kidney disease (CKD), death in the immediate postnatal period secondary to renal or respiratory insufficiency, or even stillbirth. The value of antenatal diagnosis lies in predicting postnatal outcomes and allowing for consultation of family by subspecialists.

As a general rule, unilateral anomalies, even if there is a high degree of obstruction suspected, are not related to oligohydramnios or fetal or immediate postnatal CKD, as the contralateral kidney compensates. More concerning is the fetus with suspected bilateral kidney obstruction, as is the case in bladder outlet obstruction secondary to PUV, or in a solitary kidney with any degree of abnormality.

In utero intervention

Intervention for fetal UTD generally only occurs in the setting of suspected bladder outlet obstruction. Vesicoamniotic shunting and fetal cystoscopy with PUV ablation have been studied, and shunting has been shown to offer a benefit in terms of pulmonary function and fetal survival, but no clear improvement in rate of kidney failure in these patients. There is an increased risk with fetal surgery for pregnancy loss and premature rupture of membranes, ^, so appropriate counseling is essential in a very select group of patients who may benefit. Reported combined complication rates to both mother and baby are estimated at greater than 40%. ^,

The Society of Fetal Urology held a multidisciplinary panel in 2016 to discuss antenatal intervention and to create a discrete classification system to help identify appropriate patients recommended for these interventions. The most favorable outcomes were demonstrated in fetuses with oligohydramnios but not anhydramnios, severe UTD, favorable fetal biochemistry, and absence of renal cortical cysts. Fetal urine testing is considered favorable after 20 weeks’ gestation with urinary sodium < 100 mEq/L, chloride < 90 mEq/L, osmolarity < 200 mEq/L, and β ₂ -microglobulin < 6 mg/L. Serial sampling over 48- to 72-hour intervals was shown in one study to be a more accurate estimator of irreversible renal damage with sequential rises in the urine tests to be more predictive of an unfavorable prognosis. If in utero intervention is considered, prenatal counseling should include a maternal-fetal medicine specialist, pediatric nephrologist, urologist, and neonatologist, and a shared decision-making approach should be taken.

Postnatal evaluation and management of urinary tract dilation