PEDIATRIC UROLOGY

Clinical Significance of Primary Vesicoureteral Reflux and Urinary Antibiotic Prophylaxis after Acute Pyelonephritis: A Multicenter, Randomized, Controlled Study
Garin EH, Olavarria F, Garcia Nieto V, Valenciano B, Campos A, Young L
Department of Pediatrics, University of South Florida, Tampa, Florida, USA
Pediatrics. 2006; 117: 626-32; Comment in: Pediatrics. 2006; 117: 919-22

• Objectives: To evaluate the role of primary vesicoureteral reflux (VUR) in increasing the frequency and severity of urinary tract infections (UTIs) and renal parenchymal damage among patients with acute pyelonephritis and to determine whether urinary antibiotic prophylaxis reduces the frequency and/or severity of UTIs and/or prevents renal parenchymal damage among patients with mild/moderate VUR.
• Methods: Patients 3 months to 18 years of age with acute pyelonephritis, with or without VUR, were assigned randomly to receive urinary antibiotic prophylaxis or not. Patients were monitored every 3 months for 1 year. Dimercaptosuccinic acid renal scans were repeated at 6 months or if there was a recurrence of febrile UTI. Urinalysis and urine culture were performed at each clinic visit. Renal ultrasound scans and voiding cystourethrograms were repeated at the end of 1 year of follow-up monitoring.
• Results: Of the 236 patients enrolled in the study, 218 completed the 1-year follow-up monitoring. Groups were similar with respect to age, gender, and reflux grade distribution for those with VUR. No statistically significant differences were found among the groups with respect to rate of recurrent UTI, type of recurrence, rate of subsequent pyelonephritis, and development of renal parenchymal scars.
• Conclusions: After 1 year of follow-up monitoring, mild/moderate VUR does not increase the incidence of UTI, pyelonephritis, or renal scarring after acute pyelonephritis. Moreover, a role for urinary antibiotic prophylaxis in preventing the recurrence of infection and the development of renal scars is not supported by this study.
  
  
• Editorial Comment
  The authors present a very important study of the effects of reflux on the outcome of patient with UTIs and the benefits of prophylactic antimicrobials. Their findings suggest: 1) that reflux is not a cause of UTIs (many studies would support this notion, as an abnormality of host resistance is more likely); 2) that reflux is not associated with a statistically significant increase in pyelonephritis or renal scarring (the former tends to disagree with the previous literature and the latter is in agreement with the literature); 3) and strikingly, that antibiotic prophylaxis was associated with more UTIs and pyelonephritis than those on no therapy (a very controversial finding).
  The findings, especially that prophylaxis was of no benefit (and might have been harmful), are important and suggest a change in clinical management. On the other hand, there are some significant weaknesses in this study. First, the study was not blinded. The control group was not on any medications (vs. being treated with placebo). Hence these patients may have been evaluated differently. Indeed, some of them must have been treated with antibiotics for other illnesses during the study (e.g. ear infections). There is no mention of this. Second, the statistical analysis excluded patients who were non-compliant. A more appropriate analysis would have been an “intention to treat” analysis. Furthermore, the authors state that they needed 60 patients in each group for appropriate recruitment, hence the study was underpowered. Third, clinicians have been aware that abnormalities of host resistance are the main cause of UTIs, but the authors make no mention of voiding dysfunction or constipation. Fourth, the study only lasted 1 year and during that time, only 20% of the patients resolved their reflux. To answer the question that the authors attempt to deal with, a much longer follow-up period is needed.
  Despite these misgivings, the authors did find a much higher rate of pyelonephritis in those getting prophylaxis than in those on no medications (12.9% vs 1.7%). This finding is very provocative and warrants further scientific study. If substantiated, this could lead to a paradigm shift in the management of children with reflux.

Dr. Barry A. Kogan
Chief and Professor of Urology and Pediatrics
Albany Medical College
Albany, New York, USA