Interventions for primary vesicoureteric reflux.

BACKGROUND: Vesicoureteric reflux (VUR) results in urine passing retrograde up the ureter. Urinary tract infections (UTI) associated with VUR have been considered a cause of permanent renal parenchymal damage in children with VUR. Management of these children has been directed at preventing UTI by antibiotic prophylaxis and/or surgical correction of VUR. The optimum strategy is not clear.

OBJECTIVES: To evaluate the benefits and harms of different treatment options for primary VUR.

SEARCH STRATEGY: In August 2010 we searched CENTRAL, MEDLINE and EMBASE and screened reference lists of papers and abstracts from conference proceedings.

SELECTION CRITERIA: RCTs in any language comparing any treatment of VUR including surgical or endoscopic correction, antibiotic prophylaxis, non-invasive non-pharmacological techniques and any combination of therapies.

DATA COLLECTION AND ANALYSIS: Two authors independently searched the literature, determined study eligibility, assessed quality, extracted and entered data. We expressed dichotomous outcomes as risk ratios (RR) and their 95% confidence intervals (CI) and continuous data as mean differences (MD) and their 95% CI's Data were pooled using the random effects model.

MAIN RESULTS: Twenty RCTs (2324 children) were included. Long-term low-dose antibiotic prophylaxis compared to no treatment/placebo did not significantly reduce repeat symptomatic UTI (846 children: RR 0.68, 95% CI 0.39 to 1.17) or febrile UTI (946 children: RR 0.77, 95% CI 0.47 to 1.24) at two years. There was considerable heterogeneity in the analyses and only one study was adequately blinded. At one to three years, antibiotic prophylaxis reduced the risk of new or progressive renal damage on DMSA scan (446 children: RR 0.35, 95% CI 0.15 to 0.80). Side effects were infrequent when reported, but antibiotics increased the likelihood of bacterial drug resistance threefold (132 UTIs: RR 2.94, 95% CI 1.39 to 6.25).When long-term antibiotic prophylaxis was compared with surgical or endoscopic correction of VUR plus antibiotics for one to 24 months (10 studies, 1141 children), the risk of symptomatic UTI was not significantly different at any time point. Combined surgical and antibiotic treatment caused a 57% reduction in febrile UTI by five years (2 studies, 449 children: RR 0.43, 95% CI 0.27 to 0.70) but did not decrease the risk of new or progressive renal damage at any time point. Postoperative obstruction was seen in 0% and 7% of children in two surgical studies and 0% in one endoscopic study.

AUTHORS' CONCLUSIONS: Compared with no treatment, use of long-term, low-dose antibiotics did not significantly reduce the number of repeat symptomatic and febrile UTIs in children with VUR. Considerable heterogeneity in the analyses and inclusion of only one adequately blinded study, made drawing firm conclusions challenging. Antibiotic prophylaxis significantly reduced the risk of developing new or progressive renal damage, but assuming an 8% baseline risk, 33 children would need long-term antibiotic prophylaxis to prevent one more child developing kidney damage over the course of two to three years.The added benefit of surgical or endoscopic correction of VUR over antibiotic treatment alone remains unclear. Eight children would require combined surgical and antibiotic treatment to prevent one additional child developing febrile UTI by five years, but it would not cause fewer children developing renal damage.