Megaureter and Other Congenital Ureteral Anomalies

Interestingly, Leonardo da Vinci and Galen were the first to begin to recognize the importance of the ureterovesical junction (UVJ) and to identify vesicoureteral reflux (VUR). Semblinow's 1883 animal experiments renewed enthusiasm for the study of reflux and began the modern era of research to clarify the anatomy, function, and pathophysiology of UVJ anomalies.

Megaureters

The term megaureter refers to an enlarged ureter. The 4 categories of megaureters are refluxing, obstructing, refluxing/obstructing, and nonrefluxing/nonobstructing. Each category is further divided into primary or secondary, based on either intrinsic or extrinsic causes for their appearance, as follows:

• Primary obstructed megaureter is most commonly caused by an adynamic juxtavesical segment of the ureter that fails to effectively propagate urine flow.

• Secondary obstructed megaureter occurs usually when ureteral dilatation is the result of a functional ureteral obstruction associated with elevated bladder pressures secondary to posterior urethral valves (PUV) or a neurogenic bladder that impedes ureteral emptying.

• Primary refluxing megaureter is associated with severe VUR that alters ureteral efficiency by ureteral distention. The megaureter-megacystis syndrome is an extreme form of the primary refluxing megaureters in which massive reflux prevents effective bladder emptying because urine is passed back and forth between the ureters and bladder.

• Secondary refluxing megaureter occurs secondary to PUV or neurogenic bladder when elevated bladder pressures cause decompensation of the UVJ.

• Primary nonrefluxing/nonobstructed megaureter is diagnosed when no evidence of obstruction or reflux can be demonstrated (diagnosis of exclusion).

• Secondary nonrefluxing/nonobstructed megaureter occurs secondary to diabetes insipidus, in which high urinary flow rates may overwhelm the maximum transport capacity of the ureter by peristalsis, or as the result of ureteral atony accompanying a gram-negative UTI.

• Primary refluxing obstructed megaureter occurs in the presence of an incompetent VUJ that allows reflux through an adynamic distal segment.

Vesicoureteral reflux

A sufficient tunnel length of the submucosal ureter is the most important component of a competent UVJ, as it provides a predominantly passive valve mechanism for ureteral compression and prevents retrograde urine passage. Factors that affect marginal tunnel pressure, causing either primary or secondary reflux, include the loss of UVJ compliance (during UTI), structural weaknesses in the detrusor floor (bladder diverticulum, ureterocele), or excessively high intravesical pressure resulting from neurovesical dysfunction or bladder outlet obstruction (BOO). Reflux resulting from a congenitally deficient UVJ is referred to as primary reflux; reflux resulting from a BOO or neurogenic bladder is referred to as secondary reflux.

A ureteral bud, the early precursor of the ureter, branches off from the caudal portion of the wolffian (mesonephric) duct between the fourth and sixth week of gestation. The cranial portion of the ureteral bud joins with the metanephric blastema and begins to induce nephron formation. The bud subsequently branches into the renal pelvis and the calyces and induces nephron formation. Caudally, the mesonephric duct (along with the ureteral bud) is incorporated into the cloaca as it forms the bladder trigone. Alterations in bud number, position, or time of development result in ureteral anomalies.

Early branching of a single ureteral bud results in incomplete (partial) duplication, with a single ureteral orifice and bifid proximal ureters. An accessory ureteral bud creates complete duplication, with the upper ureter usually protruding into the bladder more medially and inferiorly than the lower ureter. Ectopic termination of a single system or of the ureter of a duplex system is the result of the high (cranial) origin of the ureteral bud from the mesonephric duct. Because of the delayed incorporation of the ureteral bud into the bladder, the resulting position of the ureteral orifice is more caudal and medial or in more severe cases it inserts into one of the Wolffian duct structures as noted above.

The function of the ureter is to effectively transport the urinary bolus from the minor calyces to the urinary bladder at acceptably low pressures. The efficiency of this task depends on adequate coaptation of the ureteral wall to propel the urinary bolus. If the ureter fails to propagate the peristaltic wave, the static urine distends the upper urinary tract and reduces luminal coaptation. Other factors that may affect ureteral transport include urinary volume and bladder pressure.

Frequency

Ureteral duplication

• Ureteral duplication is the most common anomaly of the urinary tract.
• Incidence is as high as 8% in children being evaluated for UTI.
• Incomplete ureteral duplication is observed in approximately 1 in 25 individuals.
• Complete duplication is present in approximately 1 in 125 individuals.
• Complete duplication on one side results in a 40% chance of a complete duplication abnormality on the other side.
• Approximately 10% of siblings may also be affected by complete duplication.

Ectopic ureters

• Incidence is approximately 1 in 2000 newborns. ^[1]
• Approximately 10% are bilateral.
• Ectopic ureters occur more frequently in females than in males (by a ratio of 6:1).
• In females, more than 80% of ectopic ureters drain duplicated systems. In males, most ectopic ureters drain a single system.
• Approximately 80% of all ectopic ureters drain the upper pole of a duplex kidney.
• In males, the ureters always terminate proximal to the external sphincter and may be found at the bladder neck/prostatic urethra (48%), seminal vesicle (40%), ejaculatory duct (8%), vas deferens (3%), or epididymis (0.5%).
• In females, the ureters may terminate at the bladder neck/urethra (35%), vestibule (30%), vagina (25%), or uterus (5%).

Megaureters

• Bilateral involvement is present in about 20% of patients with primary obstructed megaureters.
• Primary obstructed megaureter has a male-to-female ratio of nearly 4:1.
• The left side is more often affected than the right.

Ureterocele

• Incidence is approximately 1 in 4000 children.
• Approximately 80% occur in females.
• Approximately 10% are bilateral.
• Approximately 80% are associated with duplicated collecting systems, with single-system ureteroceles being more common in males and adults.

Vesicoureteral reflux

• Incidence is approximately 1:500 children. ^[2]
• The incidence is approximately 40% in patients undergoing evaluation for UTI.
• VUR is present in 40%-50% of children with chronic kidney disease. ^[2]
• The reported risk of reflux in a sibling is 27%-43%.
• Approximately 50% of the offspring of women with reflux also have VUR.

The outcome of ureteral anomalies chiefly depends on the presence or absence of obstruction and/or infection, and associated kidney injury. In the absence of these, no treatment may be necessary, especially in the case of isolated ureteral duplication anomalies, low-grade VUR, a small orthotopic ureterocele, or a nonobstructed, nonrefluxing primary megaureter. With respect to primary megaureters, as in the case of VUR, spontaneous resolution is common. In the case of the obstructed primary megaureter, spontaneous resolution is less likely to occur; however, one study reported a 70% spontaneous regression. ^[3]

Cases of high-grade VUR are less likely to spontaneously resolve and more likely to put the kidney at risk of scarring due to pyelonephritis. Prevention of infection is essential to minimize the risk of renal damage; therefore, continuous antibiotic prophylaxis is usually used in children with high-grade VUR while awaiting spontaneous resolution. In the case of obstructive ureteroceles, treatment to relieve obstruction optimizes preservation of renal function, as chronic obstruction can lead to renal deterioration.