Primary vesicoureteral reflux (VUR) has long been considered a pathogenic factor in the development of urinary tract infections (UTIs), predisposing patients to recurrent UTIs and increasing their risk of pyelonephritis and renal scarring; however, there are no controlled studies to support this relationship. Moreover, although urinary antibiotic prophylaxis is widely used to prevent UTI sequelae in VUR patients, no randomized, prospective studies have validated this approach.OBJECTIVES
To determine whether VUR increases the risk of UTIs and renal damage in patients with acute pyelonephritis, and to investigate the therapeutic value of urinary antibiotic prophylaxis.DESIGN AND INTERVENTION
This multicenter, randomized, controlled trial recruited patients (aged 3 months to 18 years) with acute pyelonephritis, between December 1998 and December 2003. All patients underwent urinalysis, urine culture, voiding cystourethrogram, renal ultrasound, and dimer-captosuccinic-acid renal scintigraphy. Acute pyelonephritis was treated at the attending physician's discretion. Patients with grade IV-V VUR, renal failure, or urinary diversion were excluded. The remaining patients were randomly allocated to receive urinary antibiotic prophylaxis or to join an observation protocol. Randomization was stratified by VUR status. Patients in the prophylaxis group received a daily dose of either 1-2 mg/kg trimethoprim plus 5-10 mg/kg sulfamethoxazole, or 1.5 mg/kg nitrofurantoin, for 12 months. Patients in the observation group received treatment as UTIs occurred. All patients were evaluated every 3 months with urinalysis and urine culture. Repeat dimercaptosuccinic-acid renal scintigraphy was performed at 6 months, and repeat voiding cystourethrogram and renal ultrasound at 12 months.OUTCOME MEASURES
The primary endpoints were rates of overall UTI recurrence, pyelonephritis recurrence, and the development of renal scars.RESULTS
Of 218 patients with 12 months' follow-up, 113 had VUR at baseline (55 managed with antibiotic prophylaxis, and 58 managed with observation), and 105 did not (45 managed with antibiotic prophylaxis, and 60 managed with observation). In the observation group, the rate of UTI recurrence was 22.4% for patients with VUR and 23.3% for patients without VUR (P=0.9999). In the prophylaxis group, the rate of UTI recurrence was 23.6% for those with VUR and 8.8% for those without VUR (P=0.0633). The most common type of recurrence was cystitis. The rate of recurrent pyelonephritis was higher in patients with VUR than in patients without VUR (7.1% versus 3.8%), but not this was not significant (P=0.3781). Among patients with VUR, the use of antibiotic prophylaxis was associated with a significantly higher rate of recurrent pyelonephritis compared with use of the observation protocol (12.9% versus 1.7%, P=0.0291). At 12 months, 7 of 113 patients (6.2%) with VUR, and 6 of 105 patients (5.7%) without VUR, had developed renal scars (P=0.9999). Rates of scarring were similar in the two treatment groups.CONCLUSION
There were no indications that grade I-III VUR is a predisposing factor for the development of recurrent UTIs, pyelonephritis, or renal scars. Antibiotic prophylaxis did not reduce UTI recurrence or renal scarring, and thus offered no benefit over observational management.