Pediatr Nephrol (2008) 23:347–353 DOI 10.1007/s00467-007-0542-y
REVIEW
Management of fetal hydronephrosis Jenny Yiee & Duncan Wilcox
Received: 16 December 2006 / Revised: 24 April 2007 / Accepted: 26 April 2007 / Published online: 2 August 2007 # IPNA 2007
Abstract Prenatally detected hydronephrosis has become a common diagnosis for both pediatric nephrologists and urologists. Hydronephrosis is most commonly assessed by the Society for Fetal Urology grading system or anterior– posterior diameter of the renal pelvis in the transverse plane. Some cases of bilateral obstruction, most commonly from posterior urethral valves, can be life-threatening and require close monitoring or, occasionally, fetal intervention. The majority are unilateral and of no threat to the growing fetus. The crux of postnatal management is the separation of the minority of patients whose renal function is at risk from the majority who will suffer no renal consequences. This management involves a regimen of ultrasounds, voiding cystourethrograms, and nuclear renograms for diagnosis and surveillance. Recent literature has been aimed at the timing and necessity of these studies in order to minimize extraneous studies without compromising renal function.
Keywords Hydronephrosis . Prenatal ultrasonography . Radioisotope renography . Decision making
J. Yiee Urology, University of California at Los Angeles, Los Angeles, CA, USA D. Wilcox (*) Urology, The University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390-9063, USA e-mail:
[email protected]
Introduction Prior to the prenatal ultrasound era, hydronephrosis often presented symptomatically with infection or pain [1], for which surgical indications are straightforward. With the increased popularity of prenatal ultrasound (U/S) came a new urologic dilemma: the treatment of asymptomatic prenatally detected hydronephrosis. Both the etiology and the clinical outcome of hydronephrosis are widely varied [2], leading to much debate as to the significance, work-up, and management of prenatal hydronephrosis [3–7]. This review will discuss current views and literature regarding prenatal detection, prenatal intervention, and postnatal management of prenatally detected hydronephrosis.
Prenatal detection The incidence of prenatal hydronephrosis is 2–9 per 1,000 [8]. The two most common approaches to defining hydronephrosis are the Society for Fetal Urology (SFU) grade and anterior–posterior (AP) diameter. Unfortunately, no firm consensus exists as to which parameters are most clinically relevant [7]. In an attempt to develop a system that was reproducible and simple, Fernbach et al. [9] introduced the grading system used by the SFU in 1993. Grade 1 represents a split pelvis, grade 2 is further dilation of the renal pelvis, with a few visualized calyces permissible, grade 3 is renal pelvis dilation, with many distended calyces, and grade 4 is a grade 3 appearance with the addition of thinned parenchyma (Fig. 1a–e). While SFU grading is more common in North America, AP diameter measured in the transverse view of the kidney is more prevalent outside of North America (Fig. 1f). An
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Fig. 1 Ultrasound appearance of hydronephrosis. a SFU grade 0; b SFU grade 1; c SFU grade 2; d SFU grade 3; e SFU grade 4; f transverse plane with AP diameter indicated by white cross-marks
easily remembered value for significant hydronephrosis is >10 mm [10]; however, further studies have shown that smaller diameters may be significant if associated with calyceal dilatation. As with most detection criteria, the determination of cut-off points involves a balance between sensitivity and specificity. Toiviainen-Salo et al. [11] have presented data showing that 100% sensitivity can be achieved with an AP diameter >4 mm prior to 33 weeks gestation and >7 mm after 33 weeks, but this comes with a 30–80% false positive rate. The false positive rate can be lowered to 15% with an acceptable 80% sensitivity at values >4 mm prior to 24 weeks and >10 mm after 24 weeks. The third-trimester sonogram has the highest positive predictive value (PPV) in predicting further urologic abnormality [4]. The PPV for an AP diameter >7 mm in the third trimester is 69%, versus a 49% PPV for an AP diameter >4 mm in the second trimester. Similarly, Wollenberg et al. showed that no children with an AP diameter <10 mm went on to experience urinary tract infections (UTIs) or require surgery, whereas 23% of patients with AP diameters 10– 15 mm and 64% of patients with AP diameters >15 mm required such postnatal treatment [12]. Though the majority of cases are unilateral, 17–30% [4, 13, 14] are bilateral. Bilateral hydronephrosis is of more concern and requires a careful approach in investigating underlying lower urinary tract obstruction (e.g. posterior urethral valves in boys) and preservation of renal function. A poor prognostic sign in bilateral hydronephrosis is the development of oligohydramnios earlier than the third trimester [15]. Postnatal imaging of prenatally detected hydronephrosis shows resolution on postnatal ultrasound in 48% of patients, a non-obstructed enlarged pelvis (including extrarenal anatomy) in 15%, ureteropelvic junction obstruction in 11%, vesicoureteral reflux in 9%, megaureter in 4%, multicystic dysplastic kidney in 2%, ureterocele in 2%, renal cyst in 2%, and posterior urethral valves in 1% [2].
Less common causes include ectopic ureters, prune-belly syndrome, urethral atresia, retrocaval ureter, ureteral stricture, hydrocolpos, pelvic tumor, or cloacal abnormality [16]. Distinction between these etiologies can usually be determined on postnatal examination and radiographic studies.
Prenatal management The goals of prenatal intervention are to preserve renal function and provide the necessary aqueous environment for lung maturation. Prenatal assessment should consider unilaterality versus bilaterality, presence of oligohydramnios, presumed postnatal diagnosis, evidence of dysplasia on renal ultrasound, renal function as measured by amniotic electrolytes in severe cases, and concurrent congenital diagnoses. Management options include follow-up ultrasounds in utero, follow-up imaging postnatally, termination of pregnancy, induced early delivery, fetal surgery, and vesico-amniotic shunting [15]. Unilateral hydronephrosis rarely requires intervention, as a normal contralateral kidney will prevent oligohydramnios and intervention has not been proven to improve outcomes [17]. One scenario in which intervention can be considered is the case of severe hydronephrosis causing compression of neighboring organs, specifically the lungs. Intervention in bilateral hydronephrosis is generally limited to boys with outlet obstruction who develop oligohydramnios [17]. The most common causes of obstruction are posterior urethral valves and urethral atresia, though severe hydronephrosis due to reflux and obstructing ureterocele have been reported [18, 19]. Extensive counseling with parents is needed in order for a course of action to be determined. Specific issues to be addressed are the high mortality rate with or without intervention, long-term outcomes with intervention, and a high complication rate [18–20].
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The timing and outcome of prenatal intervention is still a topic of controversy. One variable that may affect prognostic counseling is fetal renal status, as assessed by percutaneous bladder aspiration. The ability of fetal urine sampling to accurately predict renal outcome is not firmly accepted, but it provides some insight into the fetal kidney’s function. Fetal urine is hypotonic, with normal parameters of sodium <100 mmol/l, chloride <90 mmol/l, calcium <2 mmol/l, osmolarity <200 mmol/kg, β-2 microglobulin <508 mmol/l, and total protein <0.2 g/l, although these values do change during gestation [21]. Some authors have suggested that the sensitivity and specificity of sampling can be improved with sequential sampling of three specimens 48–72 h apart [22]. The use of sequential specimens attempts to eliminate the possibility of electrolyte shifts and protein degradation in stagnant urine. Decreasing values with serial sampling suggest favorable renal function. Other parameters that should be considered include the ultrasound appearance of the kidneys, to exclude dysplastic (and, thus, poor prognostic) kidneys, chromosome analysis, to exclude anomalies and confirm male gender, and gestational age, as oligohydramnios earlier than the third trimester carries a worse prognosis from pulmonary and mortality standpoints [15, 23, 24]. Survival of patients without intervention ranges from 0% in those with poor prognosis by urinalysis to 42% in those with a good prognosis. Intervention raises these rates to 38% in those with a poor prognosis and 69% in those with a good prognosis. An analysis of the five largest published series by Coplen revealed an overall survival rate of 47% in those with successful shunt placements [15]. Success of shunt placement and retention in proper position is not guaranteed. In a 10-year series with ten patients, Coplen et al. reported a 50% rate of successful shunt placement. Only 50% of these successful shunts remained in place for the duration of gestation [19]. In addition, the rate of shunt-related complications in this series was 50% and included retraction requiring laparotomy, evisceration, premature labor, and death. The successful placement of a shunt still requires longterm multi-specialty follow-up. In two large studies with 4-to-5-year follow-up, postnatal mortality in those with successful shunts ranged from 9% to 34% [18, 24]. The most common cause of death in both series was pulmonary hypoplasia. Some 43–67% of patients will have asthma or pulmonary infections later in life; however, only 0–11% will have restrictions in daily activities secondary to pulmonary issues. When renal function was assessed, 33–36% had renal failure, 21–22% had renal insufficiency, and 45–46% had normal renal function. The need for intermittent catheterization varied from 33–43% for bladder dysfunction, though most are continent. In a quality-of-life survey, those with a history of shunts reported the same satisfaction with life as did healthy subjects [24].
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Other prenatal interventions for bilateral hydronephrosis are fetal surgery and induced delivery. No studies exist as to the utility of early delivery. Open fetal vesicostomies and ureterostomies have been performed in the past; however, due to concerns of morbidity those techniques are no longer used [25, 26]. Endoscopic placement of vesico-amniotic shunts, and ablation of valves have been described both from antegrade and retrograde approaches [27, 28]. Some possible advantages of treating valves as opposed to placing shunts are that the bladder is allowed to develop with physiologic urine cycling, the possibility of shunt migration is eliminated, and similar caliber instrumentation to that for vesico-amniotic shunts is used.
Postnatal management Do all babies with abnormal prenatal ultrasound findings, even those with mild or transient cases, need postnatal studies? Ismaili et al. showed that dilations detected only in the second trimester, but resolved in the third trimester, still have a 12% incidence of significant pathology [4]. Morin et al. have studied the natural history of minimal prenatal hydronephrosis. Inclusion criteria included an AP diameter of 4–10 mm prior to 20 weeks gestation and 5–10 mm at 20–24 weeks gestation. Subsequent prenatal imaging showed worsening in 9%, stability in 25%, and resolution in 35%. Six percent were found to have severe ureteropelvic junction (UPJ) obstruction with a differential renal function <40% or grade IV reflux [14]. Although there are few data to support it, most urologists recommend prophylactic antibiotics and at least one postnatal ultrasound in all patients with a history of antenatal hydronephrosis. Postnatal ultrasound findings will be normal in 21–28% of patients referred for prenatal hydronephrosis [29, 30]. Timing of the first postnatal ultrasound has been studied, given the concerns for false negatives with dehydration and a low glomerular filtration rate immediately after birth. Wiener and O’Hara performed ultrasounds at 2 days and 7–10 days postnatally in 21 patients [31]. They found an increase in hydronephrosis in 44%, a decrease in 25%, and no change in 31%. Though it is of concern that almost half of hydronephrosis had worsened by the second ultrasound, none of these patients went on to require surgery, making the second ultrasound findings of questionable clinical significance. This would suggest that an ultrasound within 48 h is adequate in detecting clinically significant disease. This study confirmed a prior retrospective study by Docimo and Silver, who reviewed the records of 101 patients [32]. At a 48 h postnatal ultrasound, 58% of those children had resolved or mild hydronephrosis. None of these patients went on to require surgery in the first year of follow-up. All patients who did require surgery for reflux or
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obstruction had positive ultrasound findings at 48 h. The practical advantage of a 48 h ultrasound is the unburdening of the family from having to return to the hospital soon after discharge. In deciding whether one normal ultrasound finding is sufficient to end the work-up of prenatal hydronephrosis, physicians must weigh the risks of an additional future ultrasound with that of missing an abnormality. As the risks of ultrasound are minimal, and the consequences of missed abnormalities are high, many physicians still obtain a later follow-up ultrasound for all patients, to confirm resolution and rule out developing pathological conditions [32]. Some do not follow patients with AP diameters <15 mm, given the minimal chance of significant disease [13]. Others would perform voiding cysto-urethrography (VCUG) on all patients with a history of prenatal hydronephrosis, regardless of postnatal ultrasound findings [16]. An algorithm for the management of hydronephrosis is presented in Fig. 2. The traditional algorithm for the evaluation of hydronephrosis is to perform VCUG in the first week of the baby’s life [33], as VCUG to detect reflux would potentially save asymptomatic children from future renal damage. Patients with complicating criteria who should undergo VCUG are listed in Fig. 3. In patients whose condition is straightforward, with no complicating criteria, some authors question the blanket need for VCUG [34]. Limiting unnecessary tests is particularly salient to VCUG, as, unlike ultrasound, VCUG is invasive and distressful to the child and
Prenatal Hydronephrosis Ultrasound in Postnatal Week 1 AP diameter <15 mm Discharge
Unilateral*
Bilateral*
Observe 8-12 Weeks
1.VCUG & MAG-3 2. Observation±,*
Ultrasound Persistent Hydronephrosis (SFU >2)*
1. MAG-3 Renogram* 2. Observation±,*
Improved Hydronephrosis
Discharge
* Criteria for Surgery • AP diameter >30 mm • AP diameter >20 mm with calyceal dilation • Renal function <30% • Worsening renal function • Worsening hydronephrosis • Symptoms ±
Observation protocol • Prophylactic antibiotics • Renal ultrasound every 2-12 months • Repeat MAG-3 for worsening ultrasound or symptoms • Discharge when improved and stable • Surgery as described above*
Fig. 2 Algorithm for management of prenatally detected hydronephrosis (MAG-3 mercapto-acetyl-triglycine)
Fig. 3 Criteria for VCUG
• • • • • •
Bilateral hydronephrosis Duplex kidneys or ureterocele Hydroureter Thickened ureter or bladder wall Abnormal kidney parenchyma If diagnosis is in doubt
carries a significant radiation burden [35]. Some literature now suggests that reflux detected in children with mild-tomoderate hydronephrosis may not be clinically significant. Yerkes et al. [36] reviewed patients with hydronephrosis of SFU grade 2 or less. Of the patients who underwent VCUG, 15% were found to have reflux. Half of those detected cases were grade III or higher. None of the patients who did not undergo VCUG experienced any infectious sequelae or renal deterioration, though follow-up was as short as 6 months in some patients. These authors concluded that VCUG is not mandatory in hydronephrosis of grade 2 or less if close follow-up and antibiotic prophylaxis is possible. Ismaili et al. [29] prospectively studied 264 infants with prenatally diagnosed hydronephrosis. All had received ultrasounds at 5 days and 1 month and had undergone VCUG. In infants with an ultrasound showing AP diameter >7 mm, 40% had abnormal VCUG findings. In infants with an ultrasound showing a normal diameter, but other abnormalities, such as renal dysplasia, ureteral dilation, or pelvic or ureteral wall thickening, VCUG gave abnormal findings in 24%. In those with two normal post-natal ultrasounds, VCUG results were abnormal in only 6.7%. This finding provides another useful parameter for choosing which patients may not need to undergo VCUG. In spite of this information, many physicians still perform VCUG in all cases of prenatal hydronephrosis [37–40]; however, a more selective approach now seems reasonable. A renogram is usually obtained at 8–12 weeks to allow for maturation of kidney function, but no studies exist as to the utility or timing of postnatal renograms. A renogram in those with suspected UPJ obstruction estimates baseline differential function and rapidity of radiotracer washout. Not all patients may need a renogram, especially those with mild hydronephrosis. Bergu et al. [41] found that all patients with AP diameters <20 mm and all patients with SFU grades 1 and 2 hydronephrosis had differential renal functions >40%. Of patients with stable or improved hydronephrosis, 88% had stable renal function. Therefore, in general, additional renograms on a watchful waiting regimen can be reserved for patients with worsening ultrasound findings. The most common nuclear renogram to evaluate differential function and drainage is that using mercaptoacetyl-triglycine (MAG-3), which is largely secreted by the
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tubules, with some filtration. Dimercapto-succinic acid (DMSA), deposits tracer in proximal tubular cells and is superior to MAG-3 in assessing cortical scars and function in the setting of reflux but is inferior in assessing drainage and is consequently used in patients with known reflux of urine. MAG-3 is given in conjunction with furosemide in order to obtain a washout curve [42]. Clearance of the tracer can be dependent on many factors unrelated to obstruction of the UPJ, such as hydration status, supine versus upright positioning, size of the renal pelvis, renal function, and fullness of the bladder. For these reasons, there is a standard protocol in administration of renograms, called the “well-tempered” [43] renogram. Even with an optimal study, the finding of a prolonged T½ should not lead a practitioner to conclude automatically that an obstruction is present and that surgery is needed [44]. In fact, many physicians do not use drainage patterns at all in assessing UPJ obstruction [13, 45]. Most practitioners use drainage pattern in conjunction with differential renal function, ultrasound appearance of the kidneys, and serial examinations to optimize the interpretation of results. Ulman et al. [45] have found that patients with severe hydronephrosis and severely depressed renal function are more likely to require surgery, but these factors are not predictive. In fact, their series found that grade 4 hydronephrotic kidneys with function as low as 7% can ultimately recover without surgery. Undertaking an observational approach in such extreme cases requires intensive follow-up and reliable patients, which is often not possible.
Management of unilateral hydronephrosis While immediate repair of UPJ obstruction may have been the trend prior to the 1990s, more recent studies into the natural history of hydronephrosis suggest that the majority will resolve spontaneously without adversely affecting renal function. This new thinking started in 1990, when Ransley et al. [46] reported the results of prospectively managing the condition by serial imaging. Only 23% of those patients went on to require surgery because of worsening renal function, hydronephrosis or UTI. Further studies into this issue suggest that between 7% and 25% of patients will need surgery [47]. AP diameter of the renal pelvis, and SFU grade, may be predictive of the need for surgery. Dhillon has shown that an AP diameter >40 mm carries an 80% chance of surgery; >30 mm has a 55% chance of surgery, >20 mm has a 20% chance of surgery, and <20 mm has only a 1–3% chance of surgery [13] when the indications for surgery are differential function <40% or symptoms such as pain or infection. Coplen et al. performed a prospective study, following
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patients in utero and postnatally with a standardized imaging protocol [48]. Patients underwent surgery under strict criteria, defined as worsening renal function, increasing hydronephrosis, or symptoms such as infection. The authors were able to show that the use of a 15 mm cut-off point correctly identifies the need for future surgery 80% of the time. A meta-analysis by Sidhu et al. showed that 98% of patients with SFU grades 1 or 2 will improve, while only 51% of those with grades 3 and 4 will improve [7]. These cut-off points can aid physicians in the timing and frequency of surveillance imaging by identifying those at greater risk of deterioration. Our criteria for surgery are included in Fig. 2, though surgical indications will vary with individual surgeons. The most common surgical technique is the Anderson–Hynes open dismembered pyeloplasty in which the diseased segment of UPJ is excised and the remaining edges are sewn together. This gold standard operation combines a 98– 99% success rate [49, 50] with a complication rate of 13%. Newer approaches, such as laparoscopic or robot-assisted pyeloplasties appear to have similar success rates [51] and are becoming particularly attractive in older children, where laparoscopic techniques are easier to perform and postoperative pain control and cosmesis are of greater importance.
Management of bilateral hydronephrosis The differential diagnosis of bilateral hydronephrosis by postnatal ultrasound can include posterior urethral valves, bilateral UPJ obstruction, bilateral reflux, prune-belly syndrome, dysfunctional voiding, and urethral atresia. All patients with bilateral hydronephrosis should be started on prophylactic antibiotics and receive a voiding cystogram within the first week of life. The need for an immediate cystogram in this case contrasts with the option in unilateral hydronephrosis, which is to defer or decline VCUG. If posterior urethral valves are diagnosed, a catheter should immediately be placed for bladder drainage. The definitive treatment of choice is cystoscopic valve ablation [52].
Additional etiologies in hydronephrosis Megaureter The goal in tests for this condition is to determine the roles of reflux or obstruction in the megaureter. Ultrasound will distinguish this entity from ureteropelvic junction obstruction by the lack of a dilated ureter in the latter. VCUG should evaluate reflux. A nuclear renogram, most commonly one using MAG-3, is also performed to identify obstruction; however, interpretation of obstruction by renogram is notoriously difficult. Based on the above findings the child is then placed on a treatment regimen for
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reflux, monitored by serial examinations, or is recommended for surgery [53]. Multicystic dysplastic kidney As this diagnosis requires no surgical intervention, accurate distinction from UPJ obstruction is important. The appearance of this entity on ultrasound is of variably sized, randomly distributed cysts, as opposed to UPJ obstruction, where there is one central dominant cyst (the renal pelvis) connecting to smaller, peripheral cysts (calyces). When the diagnosis is not clear, a nuclear renogram can be obtained to evaluate function, of which there would be none in a multicystic dysplastic kidney [54]. If a multicystic kidney is present, VCUG can also be performed, as there is a 15% risk of contralateral reflux into the remaining solitary kidney, although this is usually unnecessary [55]. Renal duplication/ureterocele/ectopic ureter Many ureteroceles and ectopic ureters are associated with the upper pole of duplicated kidneys, especially in girls. Ultrasound can usually demonstrate the presence of a duplicated system, a thin ureterocele wall in the bladder, and dilated ureters. VCUG can identify a ureterocele as well as investigate for reflux. A renal scan, most commonly a DMSA scan, is obtained to document function of the upper pole in the case of duplicated systems [56]. Prune-belly syndrome The definition for this syndrome includes abnormal abdominal muscles, bilateral cryptorchidism, and dilated ureters. This syndrome can be suspected via prenatal ultrasound findings. Postnatal evaluation should first involve a cardiopulmonary examination, as this is the most life-threatening, followed by an U/S to evaluate the kidneys, ureters, and bladder. VCUG is not routinely performed, as the introduction of bacteria from a catheter can have serious consequences of infection [57].
Conclusion While prenatal hydronephrosis can have serious consequences, including death, most cases, especially unilateral, do not cause morbidity. Studies have shown that, in the majority of patients with prenatal hydronephrosis, the condition will resolve spontaneously. This is especially true for those with AP diameters <15 mm and SFU grades 1 and 2. Ultrasounds, cystograms, and nuclear renograms have allowed physicians to diagnose accurately the causes of hydronephrosis. These tests are used to monitor the patient’s anticipated improvement while guarding against worsening hydronephrosis or function which may require surgical intervention. The optimal surveillance protocol is still under debate.
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