Vesicoureteral reﬂux (VUR) is deﬁned as the retrograde ﬂow of urine from the bladder into the ureter and, in many cases, the renal pelvicalyceal system. This condition is considered problematic because it facilitates propulsion of bacteria toward the kidneys, which can cause recurrent pyelonephritis, renal scarring, and eventual renal dysfunction.
VUR is generally diagnosed during childhood. The overall incidence has been difﬁcult to estimate because the condition is often undetected and frequently resolves with age. It has been reported, however, that 70% of infants who have urinary tract infections (UTIs) also have reﬂux. Although VUR is more common in male infants, it is more common in females after the ﬁrst year of life.
Normal ureteral continence relies on a valve mechanism formed as the ureter courses between the bladder mucosa and detrusor muscle before terminating at the ureteric oriﬁce. When the bladder contracts, compression of the intramural segment of each ureter prevents the retrograde ﬂow of urine.
Primary reﬂux occurs when the ureterovesical junction (UVJ) is abnormal. In nonreﬂuxing UVJs, the length of the ureter’s intramural segment is at least ﬁve times the ureteral diameter. In reﬂuxing UVJs, in contrast, the intramural segment is too short or, less often, the ureteral diameter is too wide. As a result, the valve mechanism is inadequate to prevent the reﬂux of urine during bladder contraction. Although there is a clear genetic basis for VUR, as evidenced by high rates of concordance among monozygotic twins, the genes that modulate UVJ structure have not been identiﬁed.
Secondary reﬂux occurs when there are very high ﬁlling pressures in the bladder, which overwhelm otherwise normal ureterovesical junctions. In male infants, a common cause is posterior urethral valves (see Plate 2-34), which cause congenital bladder outlet obstruction. Other causes include neurogenic bladder, dysfunctional voiding, and ureterocele (see Plate 2-26).
Although VUR is not itself a risk factor for lower urinary tract infection, it does permit the passage of bacteria from the bladder to the kidneys. Over time, repeated episodes of pyelonephritis can result in renal scarring and dysfunction, especially if infections occur in the ﬁrst year of life. In contrast, the reﬂux of sterile urine does not appear to cause renal scarring at any age. Of note, VUR also appears to be associated with a variable degree of renal dysplasia that is unrelated to infection. Indeed, both VUR and renal dysplasia could be expected to result from an abnormally caudal posi- tion of the ureteric bud on the mesonephric duct (see Plate 2-1) because this arrangement would cause both (1) suboptimal interaction between the ureteric bud and metanephric mesenchyme, as well as (2) a short intramural course for the ureter.
Presentation And Diagnosis
VUR is generally ﬁrst suspected when prenatal ultrasound reveals hydronephrosis or when a child develops a UTI. Among infants, further workup is indicated if a repeat postnatal ultrasound reveals persistent hydronephrosis. Among children, further workup is indicated if a male child has a UTI, a female child less than 5 years of age has a UTI, or a female child of any age has a febrile UTI.
The gold standard diagnostic test is a voiding cystourethrogram (VCUG). In a VCUG, the bladder is instilled with contrast and examined under ﬂuoroscopy while the patient voids. The diagnosis of VUR is established if contrast is seen entering one or both ureters. The severity of the reﬂux can be classiﬁed into one of ﬁve grades based on the International Reﬂux Grading system, as shown in the illustration on the opposite page.
Patients with bilateral high grade VUR, particularly those with renal scarring, should undergo regular eval- uation with measurement of height, weight, blood pressure, and serum creatinine concentration. Correction of any bladder or bowel dysfunction is critical, as it lowers the rate of UTIs and improves the probability that VUR will spontaneously resolve. Urinalysis should be performed on a regular basis, along with follow-up urine culture if there is evidence of bacteriuria or pyuria. Finally, ultrasound or renal scan may be performed to assess for the presence and degree of renal scarring.
The available treatment options for VUR depend on grade and laterality. They include observation with or without antibiotic prophylaxis, endoscopic bulking of the ureteric oriﬁce, and ureteral reimplantation (see Plate 10-35). The relative risks and beneﬁts of these different options remain uncertain, and as a result there is a wide variation in management strategies.
A majority of the children with low-grade primary reﬂux (grades I-III) experience spontaneous resolution, presumably because growth of the bladder leads to lengthening of the intramural ureteral segment. Thus most authorities recommend careful observation of such children and continuous antibiotic prophylaxis until the reﬂux resolves. Common agents include low dose trimethoprim-sulfamethoxazole or nitrofurantoin. Patients who have persistent reﬂux at 6 years of age that is either bilateral or associated with renal scarring may be candidates for surgical intervention. The ﬁrst-line therapy should be endoscopic injection of bulking agents adjacent to the reﬂuxing ureteric oriﬁce, a minimally invasive procedure with high success rates in this group. A majority of the children with high-grade primary reﬂux (grades IV and V) will not experience spontaneous resolution, and thus surgical treatment may be offered to lower the risk of renal scarring. Endoscopic techniques often fail to correct high-grade reﬂux, and thus open or laparoscopic reconstruction of the ureterovesical junction is typically performed. The cross trigonal ureteral implant is a popular technique (see Plate 10-35). Until the reﬂux is corrected, antibiotic prophylaxis should be provided to maintain sterile urine.