The Swedish Reflux Trial in Children: IV. Renal Damage

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Abstract

We compared the development of new renal damage in small children with dilating vesicoureteral reflux randomly allocated to antibiotic prophylaxis, endoscopic treatment or surveillance as the control group. Included in the study were 128 girls and 75 boys 1 to younger than 2 years with grade III-IV reflux. Voiding cystourethrography and dimercapto-succinic acid scintigraphy were done before randomization and after 2 years. Febrile urinary tract infections were recorded during followup. Data analysis was done by the intent to treat principle. New renal damage in a previously unscarred area was seen in 13 girls and 2 boys. Eight of the 13 girls were on surveillance, 5 received endoscopic therapy and none were on prophylaxis (p = 0.0155). New damage was more common in children with than without febrile recurrence (11 of 49 or 22% vs 4 of 152 or 3%, p <0.0001). In boys the rate of new renal damage was low. It was significantly higher in girls and most common in the control surveillance group. There was also a strong association between recurrent febrile UTIs and new renal damage in girls. Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

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Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis and renal scars? A randomized, controlled trial.

M Pennesi, Leopoldo Peratoner, Luca Ronfani … (2008)

There has been intense discussion on the effectiveness of continuous antibiotic prophylaxis for children with vesicoureteral reflux, and randomized, controlled trials are still needed to determine the effectiveness of long-term antibiotics for the prevention of acute pyelonephritis. In this multicenter, open-label, randomized, controlled trial, we tested the effectiveness of antibiotic prophylaxis in preventing recurrence of pyelonephritis and avoiding new scars in a sample of children who were younger than 30 months and vesicoureteral reflux. One hundred patients with vesicoureteral reflux (grade II, III, or IV) diagnosed with cystourethrography after a first episode of acute pyelonephritis were randomly assigned to receive antibiotic prophylaxis with sulfamethoxazole/trimethoprim or not for 2 years. The main outcome of the study was the recurrence of pyelonephritis during a follow-up period of 4 years. During follow-up, the patients were evaluated through repeated cystourethrographies, renal ultrasounds, and dimercaptosuccinic acid scans. The baseline characteristics in the 2 study groups were similar. There were no differences in the risk for having at least 1 pyelonephritis episode between the intervention and control groups. At the end of follow-up, the presence of renal scars was the same in children with and without antibiotic prophylaxis. Continuous antibiotic prophylaxis was ineffective in reducing the rate of pyelonephritis recurrence and the incidence of renal damage in children who were younger than 30 months and had vesicoureteral reflux grades II through IV.

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International system of radiographic grading of vesicoureteric reflux

K Parkkulainen, J M Smellie, T. Tamminen-Möbius … (1985)

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Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial.

Antonella Toffolo, L Tommasi, Walburga Cassar … (2008)

Febrile urinary tract infections are common in children and associated with the risk for renal scarring and long-term complications. Antimicrobial prophylaxis has been used to reduce the risk for recurrence. We performed a study to determine whether no prophylaxis is similar to antimicrobial prophylaxis for 12 months in reducing the recurrence of febrile urinary tract infections in children after a first febrile urinary tract infection. The study was a controlled, randomized, open-label, 2-armed, noninferiority trial comparing no prophylaxis with prophylaxis (co-trimoxazole 15 mg/kg per day or co-amoxiclav 15 mg/kg per day) for 12 months. A total of 338 children who were aged 2 months to <7 years and had a first episode of febrile urinary tract infection were enrolled: 309 with a confirmed pyelonephritis on a technetium 99m dimercaptosuccinic acid scan with or without reflux and 27 with a clinical pyelonephritis and reflux. The primary end point was recurrence rate of febrile urinary tract infections during 12 months. Secondary end point was the rate of renal scarring produced by recurrent urinary tract infections on technetium 99m dimercaptosuccinic acid scan after 12 months. Intention-to-treat analysis showed no significant differences in the primary outcome between no prophylaxis and prophylaxis: 12 (9.45%) of 127 vs 15 (7.11%) of 211. In the subgroup of children with reflux, the recurrence of febrile urinary tract infections was 9 (19.6%) of 46 on no prophylaxis and 10 (12.1%) of 82 on prophylaxis. No significant difference was found in the secondary outcome: 2 (1.9%) of 108 on no prophylaxis versus 2 (1.1%) of 187 on prophylaxis. Bivariate analysis and Cox proportional hazard model showed that grade III reflux was a risk factor for recurrent febrile urinary tract infections. Whereas increasing age was protective, use of no prophylaxis was not a risk factor. For children with or without primary nonsevere reflux, prophylaxis does not reduce the rate of recurrent febrile urinary tract infections after the first episode.