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Pediatric Ureteropelvic Junction Obstruction Workup

  • Author: John M Gatti, MD; Chief Editor: Marc Cendron, MD  more...
 
Updated: Apr 28, 2016
 

Laboratory Studies

Novel approaches are being studied that may be capable of identifying clinically significant ureteropelvic junction (UPJ) obstruction. These approaches are currently experimental.

Disruption of proximal tubular integrity leads to increased urinary concentrations of β2-microglobulin (B2M), which normally is resorbed from the tubular lumen via phagocytosis and lysosomal digestion. Increased urinary concentrations of B2M may indicate tubular dysfunction from the obstructive insult. Functionally significant obstruction and recovery from obstruction may be determined by following urinary concentrations of B2M.

The potential for B2M as a marker for significant obstruction is appealing; however, determination of its levels in obstructed kidneys is not routine, and various insults besides UPJ obstruction can lead to increased urine B2M levels.[15] In addition, immaturity of the nephron and a high fractional excretion of water in neonates contribute to elevated B2M levels in the absence of any identifiable renal stress. Further observations of B2M levels in urinary obstruction are necessary before this assessment can have practical application.

N-acetyl-β-glucosaminidase (NAG) is a tubular lysosomal enzyme present in the urine of children who have various renal diseases. This is currently experimental. In rats with experimental partial ureteral obstruction, the urinary concentration of NAG increases in the first 2 weeks of obstruction and decreases with the relief of obstruction.[16]

In a clinical study, NAG levels in kidneys at the time of pyeloplasty were seven times higher than those in bladder urine from normal control patients. In addition, enzyme levels in the bladder of patients 6 weeks after surgery suggested normalization of NAG excretion.

Urinary biochemical markers of renal damage someday may aid the diagnosis of clinically significant urinary obstruction. These are currently experimental. Many biologic modulators of glomerular dynamics and renal histology have been identified. The assessment of urine for growth factors (eg, epidural growth factor [EGF], platelet-derived growth factor [PDGF], and transforming growth factor beta [TGF-β]), cytokines, and vasoactive substances may be an important adjunct in evaluating obstructive uropathy in the future.[17]

One significant study analyzed urine samples of children with UPJ obstruction using various proteomic techniques that concentrate on examining polypeptides smaller than 30 kd and identified a potential polypeptide pattern that may help determine which children require surgery.

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Prenatal Evaluation

Maternal ultrasonography

Widespread use of antenatal ultrasonography[18] has opened the field of perinatal urology; however, even the most modern ultrasonographic techniques only demonstrate dilation of the renal pelvis and ureter and cannot accurately differentiate true obstruction from a harmless physiologic dilatation.

From week 16-18 of gestation onward, nearly all amniotic fluid is urine, and the renal medulla, pyramids, and sinus fat become routinely visualized by week 20. The bladder is usually visualized by week 28; accordingly, ultrasonography at week 20 and subsequent study at week 28 are recommended for fetal urinary tract evaluation.

During any session of prenatal ultrasonographic diagnosis, thoroughly investigate the following with initial study:

  • Amniotic fluid volume to rule out oligohydramnios
  • Bladder volume
  • Kidney size
  • Anteroposterior (AP) diameter of the renal pelvis
  • Any associated abnormalities

Functionally significant hydronephrosis can be determined when the AP diameter of the renal pelvis is more than 10 mm, the ratio of the renal pelvis to the AP kidney is more than 0.3, or evidence of caliectasis is present after 24 weeks of gestation.

Once significant findings are detected, monitoring progression is also important. A meta-analysis of seven studies of isolated antenatal hydronephrosis showed that 98% of patients with Society of Fetal Urology (SFU) grade 1-2 hydronephrosis (AP pelvic diameter <12 mm) resolved, stabilized, or improved during follow-up. However, some authors have suggested 5 mm during the second trimester and 8-10 mm during the third trimester as a more specific cutoff value for predicting postnatal surgical intervention.[19]

Amniocentesis and assessment of fetal urine

Amniocentesis to assess fetal tubular function and evaluation of protein in fetal serum to assess the fetal glomerular filtration rate (GFR) is rarely indicated. The goal is to identify fetuses that are at risk for total renal destruction. This may be applicable to cases of severe hydronephrosis (SFU grade 4) or solitary kidney (or strong suspicion of renal dysplasia) with oligohydramnios.

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Postnatal Evaluation

Ultrasonography

After the prenatal presumptive diagnosis of UPJ obstruction or other conditions causing hydronephrosis is made, the neonate should undergo ultrasonographic evaluation, but the timing is controversial.

Transient neonatal dehydration occurs 36-48 hours after birth; thus, follow-up ultrasonography of mild-to-moderate cases of hydronephrosis should be performed after this period. In severe cases (eg, very large renal pelvis, bilateral hydronephrosis, solitary kidney, or oligohydramnios), immediate evaluation within 48 hours must be performed; severe hydronephrosis in spite of the oliguric status of the child can suggest the need for immediate intervention.

Postnatal evaluation consists of a urinary tract study to determine whether the calyceal pelvic dilation with or without renal cortical thinning is present. The most widely used grading system of the severity of hydronephrosis on ultrasonography after birth is the SFU system, rather than the AP diameter of the renal pelvis.

The SFU grading system for hydronephrosis is as follows[20] :

  • Grade 0 - No hydronephrosis, intact central renal complex seen on ultrasonography
  • Grade 1 - Only renal pelvis visualized, dilated pelvis on ultrasonography, no caliectasis
  • Grade 2 - Moderately dilated renal pelvis and a few calyces
  • Grade 3 - Hydronephrosis with nearly all calyces seen, large renal pelvis without parenchymal thinning
  • Grade 4 - Severe dilatation of renal pelvis and calyces with accompanying parenchymal atrophy or thinning

Other grading systems have been proposed that rely on quantitative, descriptive, or combined ultrasonographic characteristics. In 2014, a multidisciplinary consensus meeting convened to develop a hydronephrosis grading system that would be pertinent to prenatal and postnatal evaluation.[21] The group also sought to utilize standardized methods (measured and descriptive) for grading hydronephrosis by means of ultrasonography. The resultant urinary tract dilation (UTD) classification system incorporated the following six ultrasonographic parameters:

  • Anterior-posterior renal pelvis diameter (APD)
  • Calyceal dilation
  • Renal parenchymal thickness
  • Renal parenchymal appearance
  • Bladder abnormalities
  • Ureteral abnormalities

This system classifies on the based of gestational age and timing of detection (pre- or postnatal). In the postnatal realm, the following three categories are specified:

  • UTD P1 - APD 10 to <15mm with central calyceal dilation only
  • UTD P2 - APD >15mm with peripheral calyceal dilation or abnormal ureter(s)
  • UTD P3 - APD >15mm with peripheral calyceal dilation, abnormal parenchymal thickness, abnormal parenchymal appearance, abnormal ureter(s), or an abnormal bladder

Approximately 20% of antenatal hydronephroses are not found on postnatal ultrasonography. Evaluation of the contralateral kidney, bladder, and ureter is performed.

Voiding cystourethrography

Voiding cystourethrography (VCUG) may be helpful. Vesicoureteral reflux (VUR) has been found in as many as 40% of affected children. The degree of reflux is often low-grade, not contributing to upper urinary tract obstruction, and it is likely to spontaneously resolve. However, UPJ obstruction may also be seen with severe VUR when the tortuous dilated ureter develops a kink in the UPJ area, which is relatively fixed to surrounding structures, and may cause secondary obstruction.

Diuretic renography

Diuretic renography[22] is the most widely used noninvasive technique to determine the severity and functional significance of UPJ obstruction. Various protocols and techniques have been developed, resulting in significant variability in the interpretive criteria and results.

Although several radiopharmaceutical agents are available, technetium-99m mercaptoacetyltriglycerine (99mTc-MAG3) is the ideal tracer in the pediatric population. Strongly bound to protein, MAG3 is mainly intravascular and secreted by proximal renal tubules, with a small fraction being filtered by the glomeruli.

Another widely used tracer is technetium-99m diethylenetriamine penta-acetic acid (99mTc-DTPA), which, owing to the small size of the molecule, diffuses within both intravascular and extravascular spaces, resulting in significant background activity.[23]

Variables include the use of intravenous hydration, the dosage and timing of administration of diuretic, the requirement for bladder catheterization, the degree of pelvic dilatation, the severity of outflow obstruction, and the method of calculating the clearance after administration of the diuretic.

The rate at which tracer leaves the renal pelvis following diuretic injection, reflected in the slope of the drainage curve and often reported as T1/2 (the time required for 50% of the isotope to exit), is generally viewed as an accurate reflection of the patency of the UPJ. Rapid drainage (low T1/2) indicates no obstruction, while impaired drainage or slow or no washout (T1/2 >20 min) indicates obstruction.

One of the most useful measurements in diuretic renography is the estimate of differential renal function. This is considered significant when it is less than 40%. This percentage usually is well correlated with the half-life (T1/2) washout curve. Therefore, as stated above, many factors must be considered when evaluating the renal scan, especially in neonates. For this reason, the T1/2 of the diuretic renogram cannot be a single indicator to determine surgery, especially in the neonate.

Supranormal differential renal function of the affected kidney in UPJ obstruction can occasionally be found on renal scans and has been hypothesized to be caused by an increase in single-nephron filtration or nephron volume. However, in a study of histopathologic changes of hydronephrotic kidneys with supranormal differential renal function (DRF) assessed with intraoperative kidney biopsy at pyeloplasty, the glomerular area was not significantly larger than controls, but the probability for a larger renal glomeruli increased with decreasing DRF.[24]

Instead of increased nephron volume, the supranormal DRF can be accounted for by an increase in renal blood flow that results from tubuloglomerular feedback, prostaglandins, and the renin-angiotensin system as a protective mechanism from high intrapelvic pressure.

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Imaging Studies

Doppler ultrasonography

The development of Doppler ultrasonography has become another useful diagnostic modality in the assessment of kidneys with UPJ obstructions.[25, 26]  With this modality, intrarenal vasculature can be assessed to determine the resistive index. Normal kidneys reliably demonstrate resistive indices less than 0.7, and obstructed kidneys show higher values. Administration of diuretics can aggravate the preexisting obstruction, thereby aiding the diagnosis by Doppler ultrasonography. It is especially reliable in the preoperative diagnosis of aberrant accessory blood vessels associated with UPJ obstruction.

Intravenous pyelography

Intravenous pyelography (IVP) has been used to evaluate UPJ obstruction, but it may not provide enough information to determine true obstruction, and it is especially difficult to interpret in children.

IVP provides information about the obstruction and contralateral side and especially facilitates operative planning; however, infant urograms are compromised by immature renal function, which impedes adequate visualization of the collecting system. Bowel gas and underlying bony structures also make interpretation of the urogram difficult. Despite such shortcomings, IVP accurately visualizes kidney, renal pelvis, ureter, and the exact point of obstruction. IVP also allows clear visualization of malrotated renal units.

The drawbacks of IVP include the necessity of dehydration even in infants, which makes it a relatively risky procedure. Of course, a risk of radiation exposure exists, which can be minimized by limiting the number of films taken. Problems associated with contrast media exist, such as nephrotoxicity and anaphylactic reactions.[27] These problems can be reduced by using nonionic contrast agents.

Retrograde/antegrade pyelography

Retrograde pyelography was one of the first tools used to assess the upper ureter and renal pelvis. The role of retrograde or antegrade pyelography has become adjunctive, in that it requires general anesthesia. It is now mostly performed at the time of surgical correction of the UPJ obstruction in order to establish the exact site of the hypoplastic adynamic ureteral segment and to confirm the absence of coexisting lower ureteral obstruction.

Computed tomography

Computed tomography (CT) urography provides an accurate assessment of the significance and severity of UPJ obstruction, the precise preoperative anatomy, and the physiologic significance in a single examination. Anatomy of aberrant vessels, secondary kinks, and adhesions can also be obtained. The limitations in the application of this modality to small children, however, are the need for sedation and the exposure to radiation.

Magnetic resonance imaging

Developments in magnetic resonance imaging (MRI) technology have made it possible to image kidneys while assessing intracellular metabolic parameters independent of blood flow and tubular function. A study by Ritter et al found that MRI with contrast-enhanced magnetic resonance angiography (MRA) was a reliable means of detecting aberrant or obstructing renal arteries in children with UPJ obstruction.[28]  Magnetic resonance urography (MRU) has also been shown to have diagnostic utility and has the advantage of being able to demonstrate vascular and urinary tract anatomy.[29]

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Other Tests

Pressure flow studies

The Whitaker test, first introduced in 1973, is a pressure flow study that has proven useful in equivocal obstruction in children. The renal pelvis is accessed percutaneously, and the urine transport capability of the UPJ is challenged by infusion of extrinsic flow and simultaneous measurement of intrapelvic pressure.[30, 31]

Koff et al characterized the volume-dependent changes in pressure and classified patterns of pressure exit flow curves as simple or complex.[32] The Whitaker measurement records the response of the renal pelvis to distention, which does not truly define obstruction. In complex cases where intrinsic and extrinsic obstruction coexist, this test does not provide conclusive evidence.

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Histologic Findings

Intrinsic obstruction is evident as ureteral narrowing with angulation. During exploration, the catheter usually is passed to the renal pelvis without resistance, and this is evidence that the true narrowing is not a main pathologic change in UPJ obstruction.

Some have suggested a remnant valve may be present, and others have suggested a disproportionate abundance of longitudinal muscles as the cause of this condition. The most attractive theory is the obstruction secondary to muscular discontinuity. This absence or disorientation of smooth-muscle fibers at the UPJ is clearly evident on electron microscope evaluation, with the findings of increased ground substance and collagen fibers; therefore, conduction of the peristatic wave is impeded.

One study identified altered expression of interstitial Cajal cells in obstructed UPJ specimens, which are normally intercalated between nerve terminal and smooth-muscle cells, providing a means of transducing signals from neurotransmitters and mediating neurotransmission.[33] This suggests that UPJ obstruction may cause the failure of transmission of peristaltic waves across the UPJ, resulting in the failure of urine to be propelled from the renal pelvis into the ureter.

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Contributor Information and Disclosures
Author

John M Gatti, MD Associate Professor and Director of Minimally Invasive Urology, Department of Pediatric Surgery and Urology, Children's Mercy Hospital; Associate Professor, Department of Pediatric Surgery and Urology, University of Missouri School of Medicine at Kansas City, Missouri; Associate Clinical Professor, Division of Pediatric Urology, University of Kansas School of Medicine at Kansas City, Kansas

John M Gatti, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Urological Association, Society for Pediatric Urology, Society for Fetal Urology

Disclosure: Nothing to disclose.

Coauthor(s)

 

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Harry P Koo, MD Chairman of Urology Division, Director of Pediatric Urology, Professor of Surgery, Virginia Commonwealth University School of Medicine, Medical College of Virginia; Director of Urology, Children's Hospital of Richmond

Harry P Koo, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Surgeons, American Urological Association

Disclosure: Nothing to disclose.

Chief Editor

Marc Cendron, MD Associate Professor of Surgery, Harvard School of Medicine; Consulting Staff, Department of Urological Surgery, Children's Hospital Boston

Marc Cendron, MD is a member of the following medical societies: American Academy of Pediatrics, American Urological Association, New Hampshire Medical Society, Society for Pediatric Urology, Society for Fetal Urology, Johns Hopkins Medical and Surgical Association, European Society for Paediatric Urology

Disclosure: Nothing to disclose.

Additional Contributors

Bartley G Cilento, Jr, MD Instructor, Department of Surgery, Division of Urology, Children's Hospital of Boston and Harvard Medical School

Bartley G Cilento, Jr, MD is a member of the following medical societies: American Academy of Pediatrics, American Urological Association, Massachusetts Medical Society

Disclosure: Nothing to disclose.

Sang Won Han, MD, PhD Professor, Department of Urology, Yonsei University College of Medicine, Korea

Sang Won Han, MD, PhD is a member of the following medical societies: International Continence Society, Korean Medical Association, Korean Urological Association, European Society for Paediatric Urology

Disclosure: Nothing to disclose.

Koon Ho Rha, MD, PhD 

Disclosure: Nothing to disclose.

Hyeyoung Lee, MD, MS Clinical Assistant Professor, Department of Urology, Severance Hospital, Yonsei University College of Medicine, Korea

Hyeyoung Lee, MD, MS is a member of the following medical societies: Korean Medical Association, Korean Urological Association

Disclosure: Nothing to disclose.

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