Pediatric Ureteropelvic Junction Obstruction 

Ureteropelvic junction (UPJ) obstruction is by far the most common cause of pediatric hydronephrosis, occurring in 1 per 1000-2000 newborns. Widespread use of antenatal ultrasonography and the advent of modern imaging techniques have resulted in earlier and more common diagnosis of hydronephrosis. In the late 1800s, Trendelenburg performed the first reconstruction of an obstructed kidney rather than simple nephrectomy. Most early repairs consisted of a longitudinal incision through the narrow segment to be closed in a horizontal fashion. In 1891, Kuster successfully repaired a UPJ obstruction by ligating the renal pelvis below the obstruction and transposing the upper ureter to the renal pelvis with a side-to-side anastomosis.

The landmark development was the intravenous pyelography (IVP) developed by Swick in 1929, which actually visualized the site of obstruction. In 1936, Foley described the results of 20 pyeloplasties using YV repair. In 1946, Anderson and Hynes published their experience with an operation that included the complete transection of the upper ureter, subsequent spatulation of the ureter, and trimming of the redundant pelvis. This highly successful technique has become the criterion standard of surgical repair used today. Since then, an explosion of information has been available relating directly to the pathogenesis, diagnosis, and treatment of UPJ obstruction.

Before the advent of ultrasonography, the most common presenting symptom was pain, which was reported by approximately 50% of patients; urinary tract infection (UTI) was the second most common presentation reported, followed by hematuria. Other symptoms included abdominal masses and GI discomfort. Most patients were children, and only 25% of those with a diagnosis of UPJ obstruction were younger than 1 year. Of those infants, almost half had an abdominal mass. Approximately 50% of all abdominal masses were renal in origin, and 40% of them were associated with UPJ obstruction.

UPJ obstruction is by far the most common cause of pediatric hydronephrosis. As antenatal ultrasonography has become more popular, fetal and neonatal hydronephrosis and UPJ obstruction are found more frequently; therefore, the management of pediatric UPJ obstruction remains more important. Choosing an optimal therapeutic regimen is difficult due to the high variability in function, degree of obstruction, extent of damage, and potential for regeneration in growing kidneys.

Frequency

Obstruction occurs more commonly in boys than in girls, especially in the newborn period, when the ratio exceeds 2:1. Left-sided lesions predominate, particularly in the neonate, up to approximately 67%, and bilateral cases are observed in 10-40% of cases; however, fewer than 5% of patients require bilateral repair. This propensity of bilateral occurrence may explain the frequent coexistence of UPJ obstruction and multicystic dysplasia. One theory attributes multicystic dysplasia to complete obstruction of the upper ureter, and kidneys that are affected simply have UPJs with total occlusion of the upper ureter.

Intrinsic abnormalities

In the embryogenesis, the UPJ is formed during the fifth week. By weeks 10-12 of gestation, the initial tubular lumen of the ureteric bud becomes recanalized, and the UPJ area is the last to recanalize. Inadequate canalization of this area is the main embryological explanation of UPJ obstruction. Several growth factors may control embryogenesis of UPJ. Researchers propose that improper innervation with diminished synaptic vesicles may be a factor in the development of UPJ obstruction, and factors involved in neuronal development, such as protein gene product (PGP) 9.5 (a general neuronal marker), S-100 protein (a nerve supporting cell marker), synaptophysin (a synapse vesical marker), and nerve growth factor receptor were all decreased in the resected specimens of UPJ.

The induction of kidney mesenchyme by the ureteric bud is mediated by a transcription factor Pax-2. Other factors, such as c-ret, kdn-1, and wt1, also may be involved. A well-known growth factor, transforming growth factor β (TGF β), may account for the abnormal smooth musculature in the obstructed renal pelvis. More research certainly is needed to clarify the molecular basis of the UPJ obstruction.

This intrinsic obstruction is evident as the ureteral narrowing with angulation is found. During exploration, the catheter usually is passed to the renal pelvis without resistance, and this is evidence of the fact that the true narrowing is not a main pathologic change in UPJ obstruction. Some claimed the presence of remnant valvular mucosal folds, while others postulate the disproportionate abundance of longitudinal muscles as the cause of this condition.

The most attractive theory is that the obstruction is secondary to muscular discontinuity, which disrupts the coordinated motion of smooth muscle cells and may result in impeded transport of urine and blockage of the downward transmission of ureteral peristalsis. This absence or disorientation of smooth muscle fibers at UPJ is clearly evident on electron microscope evaluation with the findings of hypotrophy/hypertrophy of the smooth muscle and its replacement with excessive collagen, combined with diminution of nerve terminals and nerves at the stenotic portion.

Extrinsic abnormalities

Extrinsic obstructions secondary to bands, kinks, and aberrant vessels also are commonly encountered. In 40% of cases, an aberrant, accessory, or early-branching lower pole segment vessel is found and observed to compress the ureter, causing mechanical obstruction. In this case, with the increased urine volume, the UPJ angulation with intrapelvic volume expansion causes increased resistance and obstruction. Further angulation may occur as it becomes adherent to an inflammatory process. The presence of such a vessel in the vicinity of UPJ has gained recent attention after the advent of the endourological management. The anterior surface of the renal pelvis is associated with a lower pole vessel in 65% of cases, whereas the posterior surface is in contact with a vessel in 6% of the kidneys examined. This information is relevant for the endoscopic incision of UPJ, making lateral incision the only safe option.

Patients with extrinsic obstructions present rather late in childhood, with intermittent abdominal or flank pain. Horseshoe or pelvic kidney, duplex collecting systems, and other rotational abnormalities also may cause UPJ obstruction. Cases of so-called high inserted ureter–to–renal pelvis exist, but this is presumed to be a secondary phenomenon to obstruction because the ureteral insertion seems to be higher in cases of dilated renal pelvis.

The urinary drainage from renal pelvis to ureter is determined by many factors. Urine volume and flow, the degree of UPJ obstruction, the functional capacity of glomerulus and collecting system, and the compliance of renal pelvis are the 4 main variables determining the pelvic pressure. At first, in response to the increased pelvic pressure, the renal pelvis dilates and ureteral muscles show hypertrophy. In the intrarenal type of obstruction, the degree of dilation is restricted by renal parenchyme; thus, the damage usually is more severe than the extrarenal type. Parenchymal damage by UPJ obstruction is well documented by histologic changes, which are more severe in cases of differential function of less than 35%.

Experimental studies using artificially made complete obstructions showed changes that suggest the upward transmission of ureteral pressure in an obstructed kidney and the subsequent effects on tubular pressure, tubular function, renal blood flow (RBF), and glomerular filtration rate (GFR). The urinary obstruction results in the impairment of all renal functions except urinary dilution; however, the elevation of ureteral pressure above a certain point had no further effect on intratubular pressure. With complete ureteral ligation, a rise in renal pelvic pressure occurs, which is only transitory; over a period of hours, the renal pelvic pressure falls in concert with RBF. Also, the intrapelvic pressure in patients with UPJ obstruction most often is in the normal range assessed at the time of surgery. Researchers propose that the expansion of the renal pelvis is protective by dampening out of the pressure.

Koff proposed the concept of pressure- or volume-dependent flow. In instances of intrinsic obstruction, at low urinary flow rates, no obstruction exists; however, as the flow rate increases, the urinary bolus are not conducted, causing the renal pelvis to distend. This concept is called a pressure-dependent flow pattern. On the contrary, in cases of extrinsic compression usually caused by aberrant vessels, urine flow is impeded only after a definite amount of urine is collected in the renal pelvis. This is an example of volume-dependent flow, and the pressure damage is only evident intermittently; thus, the degree of damage generally is less than that of intrinsic obstruction.

Experimental results show that the release of complete ureteral obstruction of 24 hours of duration results in a near-normal GFR, but the total number of filtering nephrons is decreased causing increase in the single nephron GFR. Local production of prostacyclin and prostaglandin E₂ (PGE2) seems to affect glomerular arteriolar resistance. Tubular functions also are changed by obstruction, but the effects of obstruction on distal tubular and collecting duct physiology may not be as quantitatively significant as the effect on deep nephron function.

Most clinically observed obstructions are partial, and the models of partial ureteral obstruction have been developed. In this case, the total GFR of the obstructed kidney is decreased, and an increase occurs in the single nephron GFR. This process probably is the result of changes in the local elaboration of vasoactive peptides and cytokines.

Significant urinary obstruction invariably results in tubular dilation, glomerulosclerosis, inflammation, and fibrosis. Although not absolute, a good correlation exists between the severity of these histologic changes and the function remaining in the affected kidneys. Sclerotic glomeruli and fibrosis are reliably localized to areas of the kidney that demonstrate the most inflammatory infiltrate. The infiltrate consists mostly of mononuclear cells in both the cortex and medulla. The cells predominantly are macrophages, though a small number of T cells are present.

Elevated levels of interleukin-5 (IL-5) and eotaxin-2 were demonstrated in a study, which suggested that chemokines produced by the urothelium may be the chemoattractants for leukocytes, leading to further inflammatory cell infiltration, mast cell migration, and activation. The arrival of the infiltrating cells closely corresponds with the decrease in RBF and GFR after obstruction. Obstructed kidneys also demonstrate increases in cyclooxygenase activity and increased thromboxane synthetase. The monocytic infiltration has a role in changing the eicosanoid elaboration in the kidney, which, in turn, acts locally to decrease the GFR.

The activation of the renin-angiotensin system is a major factor in partial obstruction. Administration of the angiotensin-converting enzyme (ACE) inhibitor enalapril not only maintained RBF in partially obstructed kidneys at 3 weeks postobstruction but also prevented the histologic changes of glomerulosclerosis. The effects of obstruction are not all ischemic. Obstruction can mimic renal artery stenosis, and, because of its intense vasoconstrictor action, the resulting increase in angiotensin II (AII) leads to decreases in GFR. It is becoming increasingly clear, however, that AII profoundly affects the expression of growth factors in the developing kidney that ultimately are responsible for the changes in the histology. Up regulation of TGF β is apparent in these infiltrating cells, and the degree of up regulation correlates directly with fibrosis and collagen deposition in obstructed kidneys.

The fibrosis and microscopic deterioration of the kidney can be prevented by administration of ACE inhibitors. Experiments suggest that AII has a central role in the development of tubulointerstitial fibrosis in obstructed kidneys, because its inhibition ameliorates the severity of the leukocytic infiltration, the impairment of RBF, and the severity of fibrosis in obstructed kidneys. Other growth factors also may be relevant. A series of experiments with fetal opossum showed that administration of insulinlike growth factor 1 (IGF-1) decreased the fibrosis in obstructed fetal kidneys. No single factor or cytokine is responsible for the changes found in obstructed kidneys; however, continued investigation to prevent renal damage with medical treatment during the period of observation.

Until the 1980s the most important study was IVP. Oestling folds, which resemble UPJ obstruction, are remnants of fetal renal development. No significant renal pelvic dilation or hydronephrosis is associated with this condition; however, most hydronephrotic kidneys currently are detected prenatally.

UPJ obstruction is coexistent with other types of congenital abnormality in almost 50% of patients, and 10% of patients with UPJ obstruction show ipsilateral reflux. Voiding cystourethrogram (VCUG) is well warranted. In such cases, more severe anomalies should be treated first. Some believe that simultaneous repair of both conditions is not recommended, while others have performed simultaneous repairs with good results. There also are incidences of both the ureteropelvic and the ureterovesical junctions. In these cases, UPJ obstruction should be treated first because most distal ureteral obstructions are not severe. Duplication anomalies usually cause UPJ obstruction at the lower poles. In these cases, suspicion of vesicoureteral reflux also should be heightened.

In older children, periodic abdominal pain with vomiting is a common symptom. These symptoms are probably caused by intermittent kinking of the UPJ. Episodic flank pain following a diuresis is a common presenting feature in young adults but is uncommon in children. Rare urothelial tumors, such as benign fibroepithelial polyp or urinary stones, can mimic UPJ obstruction in children. Although rarely observed in developed countries, massive dilation of the renal pelvis and kidney fills the entire flank and abdomen. UPJ obstruction is a major cause of this condition.

Upon diagnosis of a UPJ obstruction, prompt intervention is appropriate to prevent or minimize renal damage. First, prophylactic antibiotic therapy is warranted in cases of moderate-to-severe dilatations because any UTI, especially in the neonatal period, dramatically increases the chance of fibrosis and parenchymal damage.

The authors recommend the following indications for surgical interventions: (1) ipsilateral UPJ obstruction with less than 40% of differential renal function on diuretic renograms; (2) bilateral severe UPJ obstruction with renal parenchymal atrophy; (3) obstructive pattern on diuretic renograms with abdominal mass, urosepsis, or other symptoms (eg, cyclic flank pain, vomiting); and (4) recurrent UTI under antibiotic prophylaxis.

Patients with renal function better than 40% are monitored with repeat renal scans at 3- to 6-month and 12-month intervals, and surgery is performed only when a clear deterioration in renal function is present. In cases in which the differential function is less than 10%, some recommend the insertion of a nephrostomy tube to find out whether return of function will be sufficient; however, the disadvantages of nephrostomy are inevitable bacteriuria and the practical difficulty of maintaining a tube in an infant. Performing nephrectomy is rare in UPJ obstruction; however, if the differential function is less than 10%, nephrectomy can be considered to relieve recurrent infection or renal hypertension.

The UPJ is formed during the fifth week of embryogenesis, and, by weeks 10-12 of gestation, the initial tubular lumen of the ureteric bud becomes recanalized and the UPJ area is the last to recanalize.

Inadequate canalization of this area is the main embryological explanation of UPJ obstruction. Oestling folds, which resemble UPJ obstruction, are remnants of fetal renal development. No significant renal pelvic dilation or hydronephrosis are associated with this condition; however, most hydronephrotic kidneys now are detected prenatally.

UPJ obstruction is coexistent with other types of congenital abnormality in almost 50% of patients, and 10% of patients with UPJ obstruction show ipsilateral reflux. Voiding cystourethrogram is well warranted. In such cases, more severe anomalies should be treated first. Because of the nature of the blood supply of the ureter, simultaneous repair of both conditions is not recommended. Incidences of both the ureteropelvic and the ureterovesical junctions exist. In these cases, treat UPJ obstruction first because most distal ureteral obstruction is not severe. Duplication anomalies usually cause UPJ obstruction at the lower poles. In these cases, suspicion of vesicoureteral reflux also should be heightened.

The conditions that preclude the anesthesia are contraindications. Also, other common surgical contraindications (eg, coagulation abnormalities) should be ruled out before the definitive surgical treatment is performed.