Surveillance/Observation

This management option is based on observations derived from animal and large clinical studies over the last 40 years: (1) VUR without associated infection does not induce renal injury or interfere with renal function and (2) VUR may resolve spontaneously with time. Experiment and clinical studies have demonstrated that the renal injury associated with VUR results from the acute inflammatory reaction induced by bacterial infection of the renal parenchyma (reviewed by Peters and Rushton, 2010 ). Bacterial virulence and host susceptibility factors determine the extent and reversibility of the renal injury. In the absence of high-pressure voiding, sterile VUR in itself does not seem to result in renal scarring or impair renal growth or glomerular function.

Early clinical studies observed that VUR resolved spontaneous in most children, occurring at any age. Consequently, it was difficult to predict when VUR would cease. More recent studies demonstrated that specific patient demographic factors, such as age at presentation, gender, grade of the reflux, laterality, mode of clinical presentation, and ureteral anatomy, could help delineate the rate of resolution. Repeat radiological evaluation with a voiding cystourethrogram (VCUG) or radionuclide cystogram should be repeated approximately 12 to 18 months.

Continuous Antibiotic Prophylaxis

During the 1960s and 1970s, several studies observed that renal scarring developed in 21% to 66% of children with VUR who were observed and only treated with antibiotics after an infection was diagnosed. Because it was not possible to predict which children were going to develop renal scarring, it was generally recommended that continuous antibiotic prophylaxis (CAP) should be instituted for preventing recurrent UTI. Subsequent studies demonstrated that treatment with CAP significantly reduced the incidence of renal scarring to less than 1% to 3% with low emergence of bacterial resistance. CAP was comparable with surgical intervention in preventing UTIs and renal scarring.

The most common antibiotics recommended for this purpose include trimethoprim-sulfamethoxazole, nitrofurantoin, and amoxicillin, the later primarily in infants less than 3 months of age. At prophylactic doses, these antibiotics have good urinary levels, are effective against urinary pathogens, have minimal effects on the bowel flora, and overall have minimal side effects (reviewed by Smellie, 1991 ). Children with VUR on CAP may be screened periodically (1–4 times per year) with follow-up urine cultures. Compliance rates with CAP range from 12% to 90% and is a common reason for pursuing alternative management options.

While on CAP, infection with an organism resistant to prophylaxis may occur, with rates ranging from 10% to 25%. These breakthrough infections are more frequent in girls, in children with bladder/bowel dysfunction, and those with existing renal abnormalities on dimercaptosuccinic acid (DMSA) imaging. These infections may be febrile, with lower tract symptoms only, or be completely asymptomatic (detected on surveillance urine culture). After 1 to 2 breakthrough infections, it is generally recommended to seek alternative methods of VUR treatment.

Discontinuation of CAP may be recommended after a certain age, with the rationale that new renal scarring occurs primarily in younger children. It is assumed that the mature kidneys are more resistant to injury from infection than immature ones. The exact age at which it is safe to stop CAP is not known but is assumed to be around 5 to 9 years of age. In addition, it has been observed that children with high-grade VUR and bladder/bowel dysfunction remain at risk for renal scarring and, thus, should be kept on CAP. Currently, there are no prospective studies that establish safe guidelines for stopping CAP. Consequently, it is important that children with VUR who stopped CAP be monitored for UTI and renal scarring because some patients will remain at risk despite their age.

No Antibiotic Prophylaxis

Recently, the use of CAP in children with VUR, which seemed rational for many decades, has come under increasing scrutiny. Theoretical concerns include the development of antibiotic resistance in the individual and in the community, the carcinogenic potential, and the financial cost. Parental pressure to not use CAP in children with VUR increases as access to unsupervised and general medical information becomes more readily available. Recent studies comparing the nonsurgical management of VUR with and without CAP suggested that in patients with low-grade VUR (grades 1–3), there was no significant difference in the incidence of UTI, acute pyelonephritis, and late renal scarring between the two groups. Similarly, a 2011 meta-analysis of the literature demonstrated that long-term low-dose antibiotic prophylaxis compared with no treatment/placebo did not significantly reduce repeat symptomatic or febrile UTI. However, CAP did reduce the risk of new or progressive renal damage as assessed by DMSA imaging.

It is should be noted that many of the studies currently in the literature have significant limitations that prevent the generalization of their conclusions to all children with VUR. Most studies primarily evaluated children with low-grade (grade 1–3) VUR; excluded patients that are at risk for renal damage, such as those with bladder/bowel dysfunction, recurrent UTIs, and preexisting renal scarring on DMSA imaging; and had short follow-up times. Studies recently demonstrated that CAP reduced the risk of febrile UTI and renal scarring in girls and in children with reflux grade 3 to 5 or with bladder/bowel dysfunction.

Management of Bladder and Bowel Dysfunction

Dysfunctional elimination disorders (ie, bladder and bowel dysfunction) seem to play a part in the cause and natural history of VUR. In infants, high-grade VUR is observed in association with high voiding pressures and detrusor hypercontractility. The resolution of VUR seems to correlate with the improvement in urodynamic parameters. In toilet-trained children, various forms of abnormal bladder function (ie, detrusor overactivity and dyssynergia of the detrusor and urinary sphincter) were similarly observed in association with VUR. Moreover, abnormal bowel function, such as constipation and encopresis, has been correlated with VUR and the risk of UTI (reviewed by Halachmi and Farhat, 2008 ). Given these findings, the treatment of dysfunctional elimination disorders is generally recommended for children with VUR to decrease the risk of UTI and improve the chance of VUR resolution. Treatment options include behavioral therapy; biofeedback; dietary/fluid modification; and medications, anticholinergic or alpha-blockers for the bladder and fiber or laxatives for the bowel (reviewed by Peters and colleagues, 2010).