Pediatr Nephrol (2013) 28:237–243 DOI 10.1007/s00467-012-2240-7

EDUCATIONAL REVIEW

Current management of antenatal hydronephrosis Kleiton G. R. Yamaçake & Hiep T. Nguyen

Received: 2 April 2012 / Revised: 31 May 2012 / Accepted: 31 May 2012 / Published online: 27 July 2012 # IPNA 2012

Abstract The strategy for the management of children with urinary tract anomalies has changed considerably as a result of the development of ultrasound equipment and techniques that allow for detailed fetal evaluation. Hydronephrosis is the most common urogenital anomaly detected, suggesting that an obstructive process may be potentially present. The goal of postnatal management is to identify and treat those patients whose renal function is at risk, while leaving alone the high percentage of patients who are at no risk of renal damage. This management involves a spectrum of radiological, medical, and surgical interventions for diagnosis, surveillance, and treatment. In this article, we review our current understanding of the natural history of antenatal hydronephrosis and its management. Keywords Hydronephrosis . Prenatal diagnosis . Fetal Intervention . Infants . Management . Prenatal ultrasonography

Introduction The use of prenatal ultrasound (US) has increased significantly over the past 20 years. In 1980, prenatal US was performed in 33 % of pregnancies, by 1987 in 78 %, and currently in over 90 %. The incidence of a significant structural abnormality detected by prenatal US is 1 % [1]. Congenital anomalies of the urinary system are the most common abnormalities detected during routine antenatal US (20–30 % of anomalies identified prenatally), representing a broad range of disorders, each with a myriad of prognoses K. G. R. Yamaçake : H. T. Nguyen (*) Department of Urology, Children’s Hospital Boston, Harvard Medical School, 300 Longwood Avenue, Hunnewell-353, Boston, MA 02115, USA e-mail: [email protected]

and each requiring different therapies. The major challenges of postnatal management are: (1) to distinguish between patients who are at risk for renal damage and those who have anatomic variants without consequence to renal function; (2) to maximize the detection of significant abnormalities while minimizing the use of invasive and sometimes distressing testing for children who would have no benefits from such tests and which would cause unnecessary anxiety for parents. The etiology and the clinical outcome of hydronephrosis are varied [2], leading to much debate on the significance, work-up, and management of antenatal hydronephrosis (ANH) [3–5]. In this review, we evaluate our current understanding of prenatal detection and postnatal evaluation of ANH, as well as the wide spectrum of possible interventions.

Defining and grading ANH The parameters used to define ANH and determine what will be clinically significant are controversial. Despite efforts to develop a more objective method, the classification of hydronephrosis remains somewhat subjective. Currently, the system most widely used to grade hydronephrosis is a qualitative scale, in which the degree is characterized as being mild, moderate, or severe. Several systems have been proposed in attempts to standardize this grading system, and these are used in varying degrees. Several authors have assessed the threshold for diagnosing ANH associated with abnormalities of the urinary tract. One common method of diagnosing ANH is by measuring the anterior–posterior diameter (APD) of the renal pelvis using US. The currently accepted standard for APD considered to be of clinical significance is based on the original work by Corteville et al. [4] and reiterated by other studies [6–9]. In the Corteville series, an APD of >4 mm at 33 weeks gestational age (GA) or of >7 mm at 40 weeks GA

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demonstrated a sensitivity of 100 % for the identification of those patients with abnormal renal function or those who required subsequent intervention postnatally, suggesting an upper limit threshold of ANH that requires postnatal evaluation. A number of other studies noted persistent postnatal uropathies when the APD of the fetal renal pelvis measures >6 mm at <20 weeks, >8 mm at 20–30 weeks, and >10 mm at >30 weeks gestation [10, 11]. In 1993, the Society for Fetal Urology (SFU) proposed a classification based not on the size of the renal pelvis (APD diameter), but on the appearance of the intrarenal collecting system [12]. This classification system incorporates collecting system dilation with renal parenchymal findings. The proposed SFU system is a spectrum, with grade 1 demonstrating normal parenchymal thickness and only renal pelvis splitting and grade 4 revealing distention of the renal pelvis and calyces in addition to parenchymal thinning (illustrated on the link http://www.uab.edu/images/peduro/ SFU/sfu_grading_on_web/sfu_grading_on_web.htm). It was intended that this more extensive classification of ANH might be helpful in predicting which children will require postnatal evaluation and management. It has been observed that the SFU grade of hydronephrosis correlates with the potential for postnatal resolution of the hydronephrosis. SFU grade 1 hydronephrosis resolves in approximately 50 % of patients, whereas grades 2, 3, and 4 hydronephrosis resolve in 36, 16, and 3 % of cases, respectively [13]. Unfortunately, the more quantitative grading systems, such as the SFU grading system, have failed to be adopted universally, and ANH is still a subjective determination by the interpreting physician. Because of this diversity of methods, it is important that when reporting the grading of ANH that the method used to diagnose and grade the finding is reported as well.

Etiology of ANH Various urological conditions may result in the finding of ANH. Some are associated with significant morbidity, while others have a fairly benign course. The differential diagnosis of ANH is listed in Table 1, with the incidence and prenatal US findings suggestive of the diagnosis. Hydronephrosis that is transient or mild in nature without any clinical sequelae is the most common, accounting for 50–70 % of the cases of ANH. Obstruction at the ureteropelvic junction (UPJ), either due to an adynamic segment, polyp, or crossing of lower pole vessels, accounts for another 10–30 % of cases of ANH [13]. Approximately 10–30 % of patients with ANH will have primary vesicoureteral reflux (VUR) [14]. Other causes of ANH, such as ureterovesical junction (UVJ) obstruction and posterior urethral valves (PUV) are much less common [15–17].

Pediatr Nephrol (2013) 28:237–243 Table 1 Differential diagnosis of prenatal hydronephrosis Etiology

Incidence

Prenatal ultrasound findings

Transient/physiologic

50–70 %

Ureteropelvic junction (UJP) obstruction

10–30 %

Vesicoureteral reflux (VUR)

10–40 %

Ureterovesical junction (UVJ) obstruction Multicystic dysplastic kidney (MCDK)

5–15 %

Posterior urethral valves (PUV)

1–5 %

Ureterocele

1–3 %

Isolated hydronephrosis, most often mild Moderately (10–15 mm) or severely (>15 mm) dilated renal pelvis in the absence of any dilation of ureter or bladder Variation in the degree of ANH during the time of US evaluation (in general, there are no specific US findings that are pathonomic) Hydronephrosis and dilated ureter to level of the UVJ Varying sizes of randomly located renal cysts, a large noncommunicating central cyst, and nonrenoform shape A combination of the following: posterior urethral dilatation (key hole sign); a full bladder with thickened wall; oligo- or anhydramnios; unilateral or bilateral hydronephrosis; increased renal echogenicity A cystic mass in the bladder, and hydroureteronephrosis to the level of the obstructing ureterocele

Less common etiology: ectopic ureter, urethral atresia, prune-belly syndrome, polycystic kidney diseases, and renal cysts

<1

2–5 %

US, Ultrasound; ANH, antenatal hydronephrosis

Prenatal evaluation In addition to characterizing the grade of the hydronephrosis (dilation of the renal pelvis and calyces), the antenatal US should document amniotic fluid level, the cycling of the urinary bladder, visualization of a ureter, presence of bilateral kidneys, characterization of renal cysts, and the presence of other organ system abnormalities (Table 2). While the degree of hydronephrosis appears to be essential, these additional findings often contribute to establishing the postnatal diagnosis [4] and correlations with outcomes. In the

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Table 2 Additional US findings relevant for the diagnosis of ANH Structure

Parameters

Kidney:

Renal parenchyma Echogenicity Thickness Unilateral vs. Bilateral Variation in the degree of hydronephrosis Ureteral dilation Size and emptying Posterior urethral dilation (Keyhole sign) Amniotic fluid volume Extra renal fluid (ascites) Other anomalies (Neurological and cardiac) Gender Overall growth and development

Ureter Bladder Urethra Other

ANH, antenatal hydronephrosis; US, Ultrasound

case of PUV and other obstructive conditions, amniotic fluid level is a significant predictor of renal function and clinical outcome [18]. Currently, there is no agreed-upon protocol for the antenatal follow-up evaluation once hydronephrosis is identified. In general, the frequency of follow-up US is often based on the severity of the findings and the pathology suspected. Magnetic resonance imaging (MRI) may help to better characterize urinary tract anomalies when the US findings are inconclusive or not diagnostic [19]. Coronal, sagittal, and axial images (T2weighted images obtained with sequences of single-shot fastspin echo) can demonstrate the detailed anatomy of the fetal urinary tract and provide a more accurate assessment of the pathology. It is generally agreed upon that hydronephrosis diagnosed earlier in gestation is more likely to have clinically significant postnatal pathology and thus require antenatal follow-up [20]. In addition, the resolution of hydronephrosis during the prenatal period is not likely to be associated with significant postnatal pathology [17].

amniotic fluid and, consequently, is intimately associated with renal development. The goal of fetal intervention is therefore to relieve the obstruction of the urinary tract to allow for normal renal development and to restore the amniotic fluid level to allow for normal lung development. Currently, fetal intervention is primarily for those with documented lower urinary tract obstruction. Options for fetal intervention include open fetal surgery, vesicocentesis/renal pelvis aspiration, vesicoamniotic shunt, and more experimental methods, such as fetoscopic and laparoscopic surgery. Unfortunately, an intervention can only be done later during gestation, which is frequently too late to prevent renal dysplasia [22]. Significant morbidity and mortality for both the fetus and the mother are associated with these procedures, and hence the risk and benefits of any intervention should be carefully considered. US findings and serial fetal urinalysis have been utilized to determine which fetuses are most likely to benefit from intervention—that is, those who do not demonstrate renal dysplasia (Table 3) [23]. Currently, fetal intervention is recommended in cases of a second trimester fetus with significant oligohydramnios, suspected good renal function, and the absence of other life-threatening congenital abnormalities [21].

Postnatal management In the majority of cases of ANH, no significant pathology is observed postnatally (i.e., transient or physiologic hydronephrosis). However, in 10–40 % of the cases, ANH allows for early detection of urological abnormalities. Postnatal evaluation is needed to identify the underlying pathology in order to protect renal function and prevent problems such as urinary tract infection (UTI), stone formation, and pain. However, it is not without associated disadvantages, including time and expense, discomfort and radiation exposure from radiologic evaluation, the unintended consequences of false positives, and the stress on the family. Consequently, there is significant controversy as to which infants with Table 3 Criteria for identifying candidates for fetal intervention

Prenatal intervention In rare cases, hydronephrosis (or more accurately, the underlying uropathy) progresses significantly during pregnancy, requiring consideration for prenatal intervention. The goal of fetal intervention for urological anomalies is to preserve renal and pulmonary function. Based upon animal and clinical studies, urinary obstruction can result in renal dysplasia, and relief of that obstruction can prevent dysplasia if performed early enough (reviewed by Herndon et al. [21]). Pulmonary development is dependent on sufficient

Diagnostics

Favorable findings

US findings

Echolucent renal parenchyma No other system abnormalities Normal Decreasing sodium (<100 mg/dL) Decreasing calcium (<8 mg/dL) Decreasing hypertonicity (Osm <200 mOsm/L) Decreasing B2 microglobulin (<4 mg/L) Decreasing protein (<20 mg/dL)

Karyotype Serial urine electrolytes

US, Ultrasound

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ANH require radiological evaluation and antibiotic prophylaxis. Several imaging modalities have been utilized in the evaluation of infants with ANH. US is the least invasive and the most common method of imaging the urinary tract in children. While it has the advantage of avoiding the use of ionizing radiation, US can only provide anatomic—and not functional—information, and its findings can be altered by operator skill, bladder filling, and hydration status [24]. Since infants are relatively dehydrated at birth, the initial postnatal ultrasound should be performed on the second day of life, in the absence of evidence of lower urinary tract obstruction [25]. Voiding cystourethrogram (VCUG) and radionuclide cystogram (RNC) are used for the evaluation of VUR. More precise anatomic details are provided by VCUG. Specifically, VCUG, rather than RNC, should be used in the evaluation of urethral anatomy or to rule out a bladder outlet obstruction problem. RNC has a higher sensitivity in detecting grade 2–5 reflux and lower exposure to radiation. When concerns for obstruction exist, such as at the ureteropelvic or ureterovesical junction, a diuretic diethylene triamine pentaacetic acid (DTPA) or mercaptoacetyltriglycine (MAG-3) renogram should be performed [26]. Two parameters are evaluated on the diuretic MAG-3 renogram: (1) the split renal function; (2) the half time (t½). Both parameters are considered equally in the assessment of the degree of obstruction and the need for surgical intervention. It is generally recommended that for accurate results, the diuretic renogram should be obtained after 1–2 months of age, since the newborn kidneys are immature and may be unable to respond adequately to the diuretic. Magnetic resonance urography provides a more complete characterization of urinary tract anatomy and function and offers prognostic information by evaluating the quality of the renal parenchyma and identifying uropathy [27]. However, issues such as availability, cost, and the need for sedation in most patients significantly limit the widespread application of this imaging modality. Immediate evaluation Any male fetus with antenatal bilateral hydronephrosis and a dilated bladder should undergo immediate evaluation for posterior urethral valves. In cases where PUV is suspected, prenatal consultation with urology/nephrology specialists should be considered, and a catheter should be placed for bladder drainage immediately following birth. Prophylactic antibiotics and a voiding cystogram within the first week of life are recommended. The definitive treatment of PUV is cystoscopic valve ablation. Following this intervention, long-term follow-up of bladder and kidney function is required to prevent complications, such as UTI, urinary

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incontinence, and chronic renal insufficiency. Similarly, in cases in which a diagnosis such as ureterocele, prune belly syndrome, urethral atresia, and polycystic kidney disease is suspected, consultation with urology/nephrology specialists may facilitate decision-making in terms of the timing and type of radiological evaluation and management needed. Management of children diagnosed with isolated ANH and a normal initial postnatal US Postnatal ultrasound findings will be normal in 21–28 % of patients referred for ANH [28, 29]. Isolated ANH is defined as hydronephrosis in a renal unit without any ureteral involvement. In deciding whether one normal US finding is sufficient to end the work-up of prenatal hydronephrosis, physicians must weigh the risks of an additional future US with that of missing an abnormality. Numerous studies have demonstrated that a single normal US within the first week of life is not sufficient to verify the absence of pathology. The incidence of late worsening or recurrent hydronephrosis is approximately 15 %, considering all grades of initial hydronephrosis [30–32]. Late worsening or recurrence usually occurs when the severity of the hydronephrosis is quite significant, i.e., SFU grade 3–4, and the majority of the patients are likely to be symptomatic [30]. The timing of late worsening or recurrence has been observed to range from a few months to 5–6 years [31]. Considering that the risks of an US examination are minimal and the consequences of missed abnormalities are high, many physicians still obtain a later follow-up US for all patients to confirm resolution and rule out continuing or worsening pathology [33]. Although long-term follow-up is deemed necessary, the appropriate period of surveillance has yet to be determined. It also remains to be determined whether such follow-up is warranted and cost-effective, given the low incidence of late-occurring significant obstruction. Consequently, some practitioners suggest discharging children with mild or grade 1–2 hydronephrosis on the 1-month US examination from further surveillance, with the recommendation that the child be seen again for UTI or pain [7, 34], while others recommend serial US examinations and UTI surveillance every 6 or 12 months [8] or in 2–3 years [35]. In general, it is advisable to perform a follow-up US 1– 2 years after birth to rule out recurrence of the hydronephrosis. Management of infants diagnosed with isolated ANH and an abnormal initial postnatal US Findings on the prenatal [4] and the first postnatal US [36] may be predictive of the course of postnatal pathology. Increasing degree of hydronephrosis correlates with increased risk of urological pathologies (from 10 % in the

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mild to 70–90 % in the severe group). The degree of hydronephrosis correlates with an increased risk of specific urology pathologies, such as UPJ obstruction (UPJO) and ureteral obstruction, except for VUR. Consequently, it is generally recommended that higher degrees of hydronephrosis observed pre- and postnatally require further radiological evaluation. Nevertheless, the evaluation of mild isolated ANH is controversial, with some practitioners recommending full radiological evaluation while others do not. Some studies suggest a benign natural history while others indicate progression of the hydronephrosis and subsequent need for surgical intervention. In a study of 213 infants with mild to moderate ANH, significant uropathies were seen in 39 % of the infants, although intervention was not required in most patients [37]. In another study, up to 24 % of infants with worsening of mild fetal pelvis dilation required subsequent intervention [38]. In contrast, others have observed that >95 % of infants with mild isolated ANH will resolve their hydronephrosis without any recurrence [37, 39]. Currently, it is recommended that most infants with mild hydronephrosis (SFU grade 1) be followed until they are mature enough to verbalize signs of distress. However, the ideal follow-up protocol for mild forms of hydronephrosis can only be determined with a multicenter prospective trial. Evaluation for VUR in children with isolated ANH The primary area of controversy is the role of VCUG in the postnatal assessment of ANH. Recent studies revealed that the routine use of VCUG to evaluate all newborns with prenatal diagnosis of hydronephrosis resulted in the detection of VUR in only 12–21 % of the cases [40, 41]. Although VCUG is commonly performed, it is an invasive test that exposes infants to ionizing radiation, risk of UTI, and the stress of the procedure for both the patient and the parents [28, 42]. Postnatal US may frequently be normal in infants with ANH secondary to VUR; 27 % of infants with ANH and grade 2–5 VUR had normal postnatal renal US [41, 43]. Consequently, some practitioners recommend performing a VCUG on all infants with a history of ANH, regardless of postnatal US findings [44]; others do not recommend evaluation for VUR in infants with an APD of <15 mm due to the minimal chance of significant pathology [45]. Despite the controversies expressed in the literature, VCUG is generally recommended for infants with other demonstrated abnormalities, such as bilateral hydronephrosis, ureterocele, hydroureter, thickened bladder wall, or abnormal kidney parenchyma. Antibiotic prophylaxis, if started, should be continued until the VCUG is completed. The timing of the postnatal VCUG should be individualized. In cases of suspected bladder outlet obstruction, it is imperative to exclude this diagnosis within the first days of life;

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VCUG is the “gold standard” in the diagnosis of PUV. In suspected cases of primary VUR, a VCUG can be delayed until around 1–3 months of life. Given the controversies in the management of VUR and low likelihood (10 %) of UTI in infants with ANH and VUR [46], VCUG may be deferred in many cases unless a UTI develops. The role of antibiotic prophylaxis in infants with ANH In infants with ANH, antibiotic prophylaxis is used to prevent UTI. The risk of UTI is correlated with the grade of hydronephrosis: 10 % in mild, 20 % in moderate, and 40 % in severe cases [9]. Infants with hydronephrosis and obstructive drainage patterns on the renogram are at higher risk of developing a UTI compared to those without obstructive curves [47, 48]. Girls appear to be at greater risk than boys [49]. However, the efficacy of antibiotic prophylaxis has not been proven. Some retrospective studies suggest that the use of prophylaxis reduces the rate of UTI [46], while others demonstrated no difference [50]. At present, it seems prudent to consider the use of prophylactic antibiotics in an effort to prevent UTI in high-risk infants with ANH, such as those with higher grades of hydronephrosis or hydroureteronephrosis, higher grades of VUR, or obstructive drainage patterns.

Conclusion The postnatal management of infants with a history of ANH remains controversial, particularly with regards to fetal intervention, diagnostic criteria, postnatal recommendations, and management of mild ANH. While the overall benefit of prenatal detection of hydronephrosis is debatable, it has a significant effect on fetal interventions and postnatal studies and management. Sufficient data to inform patient risk stratification are lacking. Over the past few decades, the management of ANH has tended toward a more conservative approach; however, the long-term outcomes of this approach are not yet known. Future prospective studies with a large cohort of patients are therefore needed to determine the most appropriate management of infants with ANH. Key summary points 1. Transient/physiologic hydronephrosis is the most common etiology of ANH. 2. Prenatal intervention for urological conditions is relatively uncommon and is primarily reserved for fetuses with bladder outlet obstruction and favorable US and urine electrolyte parameters.

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3. Children with a mild ANH demonstrated on postnatal US do require long-term follow-up to detect progressive obstructive uropathies. Key research points 1. Multi-institutional, prospective studies are needed to help identify the best postnatal evaluation protocol that would avoid excessive testing, while allowing for accurate detection of urological anomalies. 2. Additional research is needed for better assessment of fetal renal function, allowing for the prediction of which fetuses require intervention. 3. Less invasive and more reliable methods of fetal intervention should be identified and evaluated to allow for earlier intervention.

Questions (answer are provided following the reference list) 1. What is the most common etiology of ANH? a. Transient or physiologic hydronephrosis b. Ureteropelvic junction obstruction c. Vesicoureteral reflux d. Ureterovesical junction obstruction e. Posterior urethral valves. 2. In a fetus with ANH and suspected of having posterior urethral valves, which US factors is the most predictive of poor postnatal renal function? a. A severe degree (SFU grade 4) of hydronephrosis b. The presence of ascites c. A severe degree of calyces dilation d. The presence of oligohydramnios e. The fetus being first detected in the third trimester 3. What is the incidence of vesicoureteral reflux in children with ANH? a. <1 % b. 10–25 % c. 25–50 % d. 50–75 % e. Not known 4. Which of the following are correlated with favorable postnatal renal outcome? a. Echolucent renal parenchyma b. Stable Na concentration with serial urine sampling c. Sodium <100 mg/dL d. Calcium >8 mg/dL e. Osmolarity equal to 200–400 mOsm/ L 5. Which of the following statement are true?

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a. Repeat US imaging is not required for patients with mild hydronephrosis detected on pre- and postnatal US b. Prenatal intervention has been shown to improve the renal outcome of all fetuses with posterior urethral valves c. Variability in the degree of hydronephrosis on prenatal US imaging is consistent with the postnatal diagnosis of vesicoureteral reflux d. A and B e. None of the above

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Answers to the questions: 1. A 2. D 3. B 4. C 5. C