Treatment of vesico-ureteric reflux in children. Clinical significance of primary vesicoureteral reflux and urinary antibiotic prophylaxis after acute pyelonephritis: a multicenter, randomized, controlled study. GAX 65: new injectable cross-linked collagen for the endoscopic treatment of vesicoureteral reflux--a double-blind study evaluating its efficiency in children. Antibiotic prophylaxis and recurrent urinary tract infection in children. Is antibiotic prophylaxis in children with vesicoureteral reflux effective in preventing pyelonephritis and renal scars? A randomized, controlled trial. Prospective comparison and 1-year follow-up of a single endoscopic subureteral polydimethylsiloxane versus dextranomer/hyaluronic acid copolymer injection for treatment of vesicoureteral reflux in children. Dextranomer/hyaluronic acid copolymer implantation for vesico-ureteral reflux: a randomized comparison with antibiotic prophylaxis. Antimicrobial prophylaxis in children with urinary tract infection and vesicoureteral reflux. Vesicoureteral reflux and evidence-based management. The Swedish reflux trial in children: I. Study design and study population characteristics. Prophylaxis after first febrile urinary tract infection in children? A multicenter, randomized, controlled, noninferiority trial. Antibiotic prophylaxis for the prevention of recurrent urinary tract infection in children with low grade vesicoureteral reflux: results from a prospective randomized study. [Endoscopic and conservative treatment of vesicoureteric reflux]. Medical versus surgical treatment in children with severe bilateral vesicoureteric reflux and bilateral nephropathy: a randomised trial.
nan 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.
                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.
                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.
                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. In the experimental model glutaraldehyde cross-linked collagen GAX 65 with a collagen concentration of 65 mg./ml. has proved to have more persistent implant volume and, therefore, a better antireflux effect than GAX 35, which is injected more commonly. The aim of this study was to evaluate the potential clinical application of GAX 65.
                Ten boys and 8 girls an average of 4.6 years old presented with unilateral or bilateral primary reflux and were randomly divided into 2 groups. All refluxing ureters received 1 endoscopic subureteral injection of an average of approximately 2.9 ml. collagen. In group 1, 16 refluxing ureters were treated with GAX 65 and in group 2, 12 were treated with GAX 35. In all patients voiding cystourethrography was performed immediately after injection and 3 months postoperatively, and ultrasound was done on day 1, and at 1 and 3 months. Implant volume was calculated at the day of injection and at 3 months. The distribution of reflux grades was comparable in the 2 groups.
                Both materials had excellent injection properties. Immediately after injection all ureters were reflux-free. Of the 16 ureters treated with GAX 65 14 (87.5%) were reflux-free at the 3-month followup. Three months postoperatively ultrasound revealed an average implant volume increase of one-third. However, of the 12 ureters treated with GAX 35 reflux had resolved in 59.3% and the average implant volume had decreased by half 3 months after injection.
                Three months after endoscopic subureteral injection of GAX 65 vesicoureteral reflux was absent in 87.5% of patients. Therefore, GAX 65 has greater potential for treating reflux in the short term than GAX 35. To define the final efficacy of GAX 65 for treating vesicoureteral reflux, long-term evaluation of this series is necessary. In addition, further studies are mandatory to prove the long-term advantage of this new injectable substance. Antibiotics are widely administered to children with the intention of preventing urinary tract infection, but adequately powered, placebo-controlled trials regarding efficacy are lacking. This study from four Australian centers examined whether low-dose, continuous oral antibiotic therapy prevents urinary tract infection in predisposed children.
                We randomly assigned children under the age of 18 years who had had one or more microbiologically proven urinary tract infections to receive either daily trimethoprim-sulfamethoxazole suspension (as 2 mg of trimethoprim plus 10 mg of sulfamethoxazole per kilogram of body weight) or placebo for 12 months. The primary outcome was microbiologically confirmed symptomatic urinary tract infection. Intention-to-treat analyses were performed with the use of time-to-event data.
                From December 1998 to March 2007, a total of 576 children (of 780 planned) underwent randomization. The median age at entry was 14 months; 64% of the patients were girls, 42% had known vesicoureteral reflux (at least grade III in 53% of these patients), and 71% were enrolled after the first diagnosis of urinary tract infection. During the study, urinary tract infection developed in 36 of 288 patients (13%) in the group receiving trimethoprim-sulfamethoxazole (antibiotic group) and in 55 of 288 patients (19%) in the placebo group (hazard ratio in the antibiotic group, 0.61; 95% confidence interval, 0.40 to 0.93; P = 0.02 by the log-rank test). In the antibiotic group, the reduction in the absolute risk of urinary tract infection (6 percentage points) appeared to be consistent across all subgroups of patients (P > or = 0.20 for all interactions).
                Long-term, low-dose trimethoprim-sulfamethoxazole was associated with a decreased number of urinary tract infections in predisposed children. The treatment effect appeared to be consistent but modest across subgroups. (Australian New Zealand Clinical Trials Registry number, ACTRN12608000470392.)
                2009 Massachusetts Medical Society 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. To compare, in a prospective study, the efficacy of a single injection of polydimethylsiloxane (Macroplastique) or dextranomer/hyaluronic acid copolymer (Deflux), a new biodegradable substance, and to assess the short-term and 1-year clinical effects concerning reflux resolution and the safety of these two bulking agents. Subureteral injection of bulking agents has recently demonstrated good success rates for endoscopic treatment of vesicoureteral reflux. Macroplastique has been one of the most popular bulking agents during the past years. Nevertheless, considering the synthetic property, new biodegradable substances have become more relevant.
                From January 2000 to June 2001, 16 boys and 56 girls (total of 114 ureters) with a mean age of 34.5 months were treated endoscopically for vesicoureteral reflux. A single subureteral Macroplastique or Deflux injection was performed in 34 children (58 ureters) and 38 children (56 ureters), respectively. Both groups were comparable in terms of baseline parameters. Vesicoureteral reflux was grade II in 52, grade III in 57, and grade IV in 5 ureterorenal units. The procedure was performed on an outpatient basis, with the children under general anesthesia. In addition to the routine parameters, the follow-up evaluation consisted of renal ultrasonography and voiding cystourethrography at 3 and 12 months postoperatively.
                Endoscopic treatment was performed without any complications in all cases. At the 3-month follow-up visit, reflux was corrected in 50 (86.2%) of 58 refluxing ureters in the Macroplastique group and in 40 (71.4%) of 56 refluxing ureters in the Deflux group. At 1 year of follow-up, reflux correction was maintained in 80.9% of ureters in the Macroplastique group and in 67.6% of ureters in the Deflux group. No postoperative complications were observed in either group.
                A single subureteral injection of either polydimethylsiloxane (Macroplastique) or dextranomer/hyaluronic acid copolymer (Deflux) is an effective treatment modality for children with vesicoureteral reflux. The procedure was well tolerated, safe, and associated with low morbidity. Deflux, a new biocompatible, biodegradable substance, seems to be an alternative modality to other bulking agents for treating vesicoureteral reflux in children, with acceptable short-term and 1-year results. Dextranomer/hyaluronic acid (Dx/HA) copolymer has favorable properties for endoscopic treatment of vesico-ureteral reflux (VUR). This open, randomized study was performed to compare the efficacy and safety of Dx/HA copolymer with antibiotic prophylaxis in children with VUR.
                Children >1 year of age with VUR grade II to IV (confirmed by voiding cysto-urethrogram) received endoscopic treatment with Dx/HA copolymer (n = 40) or 12 months of antibiotic prophylaxis (n = 21). Patients in the latter group with reflux grade >or=II at month 3 received a second implantation. All patients were reassessed by voiding cysto-urethrogram at month 12. Scintigraphy and ultrasound were performed to investigate renal status.
                At month 12, 69% of patients in the Dx/HA copolymer group had reflux grade <or=I bilaterally, compared with 38% in the antibiotic group (P =.029). Of patients with reflux grade <or=I at month 3, 89% showed a sustained response at month 12. One serious adverse event was reported in the antibiotic prophylaxis group, but this was not attributed to study treatment. No other adverse events occurred.
                Endoscopic treatment with Dx/HA copolymer was more effective than antibiotic prophylaxis in alleviating childhood VUR, and there were no safety concerns with either treatment. Thirty children with urinary tract infection and nonobstructive vesicoureteral reflux have been followed prospectively for a mean of 17 months. After classification according to age and grade of reflux, 10 patients were assigned at random to treatment with antimicrobial prophylaxis alone or antimicrobial prophylaxis plus corrective surgery. Twenty other patients were also treated with antimicrobial prophylaxis alone. All were assigned at random to treatment with a single daily dose of trimethoprim-sulfamethoxazole or nitrofurantoin. Cultures of urine, complete blood cell counts, and determination of levels of aspartate aminotransferase in serum were performed regularly during follow-up. Both drugs proved effective in prevention of recurrent infection, and no significant hematologic or hepatic abnormalities were noted. Current results suggest that either prophylaxis or surgery may effectively prevent chronic pyelonephritis or reflux nephropathy, but only continuing evaluation of this group of patients will confirm these results. nan We compared the rates of febrile urinary tract infection, kidney damage and reflux resolution in children with vesicoureteral reflux treated in 3 ways, including antibiotic prophylaxis, endoscopic therapy and surveillance with antibiotics only for symptomatic urinary tract infection.
                Children 1 to younger than 2 years with grade III-IV reflux were recruited into this prospective, open, randomized, controlled, multicenter study and followed for 2 years after randomization. The main study end points were recurrent febrile urinary tract infection, renal status on dimercapto-succinic acid scintigraphy and reflux status. Outcomes were analyzed by the intent to treat principle.
                During a 6-year period 128 girls and 75 boys entered the study. In 96% of cases reflux was detected after urinary tract infection. The randomization procedure was successful and resulted in 3 groups matched for relevant factors. Recruitment was slower than anticipated but after patients were entered adherence to the protocol was good. Of the children 93% were followed for the intended 2 years without a treatment arm change. All except 2 patients completed 2-year followup scintigraphy.
                Recruitment was difficult but a substantial number of children were entered and randomly assigned to 3 groups with similar basic characteristics. Good adherence to the protocol made it possible to address the central study questions.
                Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved. 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. Antibiotic prophylaxis is given to children at risk for urinary tract infection. However, evidence concerning its effectiveness in grade I to III vesicoureteral reflux is lacking. The objective of this study was to determine whether antibiotic prophylaxis reduces the incidence of urinary tract infection in young children with low grade vesicoureteral reflux.
                Children 1 month to 3 years old with grade I to III vesicoureteral reflux were assigned randomly to receive daily cotrimoxazole or no treatment, and followed for 18 months. A urinary tract infection constituted an exit criterion. Infection-free survival rates were calculated using the Kaplan-Meier method and compared using the log rank test.
                A total of 225 children were enrolled in the study. Distribution of gender, age at inclusion and reflux grade were similar between the 2 groups. There was no significant difference in the occurrence of urinary tract infection between the 2 groups (17% vs 26%, p = 0.2). However, a significant association was found between treatment and patient gender (p = 0.017). Prophylaxis significantly reduced urinary tract infection in boys (p = 0.013), most notably in boys with grade III vesicoureteral reflux (p = 0.042).
                These data suggest that antibiotic prophylaxis does not reduce the overall incidence of urinary tract infection in children with low grade vesicoureteral reflux. However, such a strategy may prevent further urinary tract infection in boys with grade III reflux. The aim of study is to evaluate the results of endoscopic treatment of vesicoureteric reflux (VUR) comparing with conservative mode.
                In the years 2003-2006 there were forty for children in prospective randomised study enrolled and divided into two groups. Twenty two children 1-40 months old (22.9 months) were operated. Dx/Ha (Deflux) was instilled for VUR grade 3-5. The results of treatment were compared with outcome of twenty two conservatively treated randomly assigned children aged 1-32 months (mean age 13.5 months) Postoperative videourodynamic study was used to evaluate for the presence of VUR and function of the bladder and ultrasound investigation was performed too (exclusion of obstructive megaureter in operated group). There were 22 children controled after instillation. The children were followed 11-24 months. VUR was cured in 12 cases (54.5%) and improved (grade 1-2) in 5 children (66.7%). All children absolved treatment without any complications, excluding one case with obstructive megaureter after pyelonephritis diagnosed. There were 22 children evaluated in conservative group. Five children were cured (22.7%) and VUR was improved (grade 1-2) in four (18.2%)
                Endoscopic miniinvasive instillation of dextranomer is safe and effective treatment of VUR in all age groups with good therapeutical outcome and minimum of adverse effects. Nephropathy associated with vesicoureteric reflux (VUR) and urinary tract infection can result in end-stage renal failure, hypertension, or both. Whether long-term VUR contributes to these outcomes is unknown. We compared, in a randomised trial, medical with surgical management of children with bilateral severe VUR and bilateral nephropathy.
                We stratified by age and glomerular filtration rate (GFR) 25 boys and 27 girls aged 1-12 years and randomly assigned them to medical or surgical management. At enrolment and 4 years' follow-up we estimated GFR from the plasma clearance of 51Cr-labelled edetic acid (EDTA), and did intravenous urography. We also did a metastable 99mTc-labelled dimercaptosuccinic acid (DMSA) assay and contrast cystography. The change in GFR at 4 years, expressed as a percentage change between enrolment and 4 years, was available for 26 of 27 patients in the medical and 24 of 25 in the surgical group. We assessed GFR in 48 patients 10 years after enrolment.
                Mean GFR at enrolment was 72.4 mL/min per 1.73 m(2) (SD 24.1) in the medical and 71.7 mL/min per 1.73 m(2) (22.6) in the surgical group. The mean percentage change in GFR at 4 years was 2.4% (SE 4.5) versus 4.7% (5.0) in the medical and surgical groups, respectively. The difference in change in GFR at 4 years between the two groups was not significant (7.1%, 95% CI 6.4% to 20.6%).
                Our data do not lend support to the view that the outcome for renal function is improved by surgical correction of VUR in children with bilateral disease.
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.