Renal Scarring in the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) Trial.

2016

54-61

2016 Jan 7

1555-905X

<p><strong>BACKGROUND AND OBJECTIVES: </strong>The main objectives of the Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial were to evaluate the role of antimicrobial prophylaxis in the prevention of recurrent urinary tract infection (UTI) and renal scarring in children with vesicoureteral reflux (VUR). We present a comprehensive evaluation of renal scarring outcomes in RIVUR trial participants.</p>

<p><strong>DESIGN, SETTING, PARTICIPANTS, &amp; MEASUREMENTS: </strong>This multicenter, randomized, placebo-controlled trial enrolled 607 children aged 2-71 months with grade 1-4 VUR diagnosed after a first or second febrile or symptomatic UTI. Study participants received trimethoprim-sulfamethoxazole or placebo and were followed for 2 years. Renal scarring was evaluated by baseline and follow-up (99m)technetium dimercaptosuccinic acid (DMSA) renal scans that were reviewed independently by two blinded reference radiologists.</p>

<p><strong>RESULTS: </strong>At the end of the study, 58 (10%) of 599 children and 63 (5%) of 1197 renal units had renal scarring. New renal scarring did not differ between the prophylaxis and placebo groups (6% versus 7%, respectively). Children with renal scarring were significantly older (median age, 26 versus 11 months; P=0.01), had a second UTI before enrollment (odds ratio [OR], 2.85; 95% confidence interval [95% CI], 1.38 to 5.92), were more likely to be Hispanic (OR, 2.22; 95% CI, 1.13 to 4.34), and had higher grades of VUR (OR, 2.79; 95% CI, 1.56 to 5.0). The proportion of new scars in renal units with grade 4 VUR was significantly higher than in units with no VUR (OR, 24.2; 95% CI, 6.4 to 91.2).</p>

<p><strong>CONCLUSIONS: </strong>Significantly more renal scarring was seen in relatively older children and in those with a second episode of febrile or symptomatic UTI before randomization. Preexisting and new renal scars occurred significantly more in renal units with grade 4 VUR than in those with low-grade or no VUR. Antimicrobial prophylaxis did not decrease the risk of renal scarring.</p>

10.2215/CJN.05210515

Clin J Am Soc Nephrol

26555605

Development and impact of an intervention to boost recruitment in a multicenter pediatric randomized clinical trial.

2014

151-7

2014 Feb

1938-2707

<p><strong>OBJECTIVES: </strong>Our primary objective was to develop and evaluate an intervention to increase recruitment in a multicenter pediatric randomized clinical trial (RCT). Our secondary objective was to assess the impact beyond 120 days.</p>

<p><strong>METHODS: </strong>The study was conducted at 17 academic centers participating in a pediatric RCT. The intervention consisted of utilizing a recruitment assessment tool at a site visit or teleconference with key site personnel.</p>

<p><strong>RESULTS: </strong>We found a significant increase in the number of individuals enrolled for all 17 sites at 120 days postintervention (mean = 1.12 per site; median = 1 per site; 95% confidence interval = 1-2; P = .04). No significant differences were apparent beyond the first 120 days postintervention.</p>

<p><strong>CONCLUSIONS: </strong>Successful recruitment in RCTs is essential to the quality, generalizability, and cost-effectiveness of clinical research. Implementation of this recruitment intervention may effectively increase recruitment in RCTs. Beyond the first 120 days postintervention, repeated interventions may be required. What is new? Despite general and pediatric-specific challenges to recruitment in RCTs, a paucity of evidence exists on effective recruitment strategies or assessment tools to reliably enhance recruitment. We developed a recruitment intervention for use in RCTs that enables clinical researchers to enhance recruitment.</p>

10.1177/0009922813506961

Clin Pediatr (Phila)

24151147

Risk factors for recurrent urinary tract infection and renal scarring.

2015

e13-21

07/2015

1098-4275

<p><strong>OBJECTIVES: </strong>To identify risk factors for recurrent urinary tract infection (UTI) and renal scarring in children who have had 1 or 2 febrile or symptomatic UTIs and received no antimicrobial prophylaxis.</p>

<p><strong>METHODS: </strong>This 2-year, multisite prospective cohort study included 305 children aged 2 to 71 months with vesicoureteral reflux (VUR) receiving placebo in the RIVUR (Randomized Intervention for Vesicoureteral Reflux) study and 195 children with no VUR observed in the CUTIE (Careful Urinary Tract Infection Evaluation) study. Primary exposure was presence of VUR; secondary exposures included bladder and bowel dysfunction (BBD), age, and race. Outcomes were recurrent febrile or symptomatic urinary tract infection (F/SUTI) and renal scarring.</p>

<p><strong>RESULTS: </strong>Children with VUR had higher 2-year rates of recurrent F/SUTI (Kaplan-Meier estimate 25.4% compared with 17.3% for VUR and no VUR, respectively). Other factors associated with recurrent F/SUTI included presence of BBD at baseline (adjusted hazard ratio: 2.07 [95% confidence interval (CI): 1.09-3.93]) and presence of renal scarring on the baseline (99m)Tc-labeled dimercaptosuccinic acid scan (adjusted hazard ratio: 2.88 [95% CI: 1.22-6.80]). Children with BBD and any degree of VUR had the highest risk of recurrent F/SUTI (56%). At the end of the 2-year follow-up period, 8 (5.6%) children in the no VUR group and 24 (10.2%) in the VUR group had renal scars, but the difference was not statistically significant (adjusted odds ratio: 2.05 [95% CI: 0.86-4.87]).</p>

<p><strong>CONCLUSIONS: </strong>VUR and BBD are risk factors for recurrent UTI, especially when they appear in combination. Strategies for preventing recurrent UTI include antimicrobial prophylaxis and treatment of BBD.</p>

10.1542/peds.2015-0409

Pediatrics

26055855