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Why Does Prevention of Recurrent Urinary Tract Infection not Result in Less Renal Scarring? A Deeper Dive into the RIVUR Trial.

ABSTRACT: PURPOSE:The RIVUR (Randomized Intervention for Children with Vesicoureteral Reflux) trial reported that antibiotic prophylaxis reduced recurrent urinary tract infection but antibiotic prophylaxis was not associated with decreased new renal scarring. However, the original reports did not assess the relationship among recurrent urinary tract infection, new renal scarring and antibiotic prophylaxis in detail. Therefore, we investigated the relationship among these issues. MATERIALS AND METHODS:We included subjects with dimercaptosuccinic acid scan within 6 months of enrollment and at least 1 followup dimercaptosuccinic acid scan from the RIVUR trial. The primary outcome was recurrent urinary tract infection associated new renal scarring, defined as recurrent urinary tract infection and new changes on dimercaptosuccinic acid scan. Due to a low number of events, propensity score was used to adjust for confounders. Multivariate logistic regression was fitted to investigate the associations between the covariates and the outcome. RESULTS:A total of 489 patients (91% female, mean age 20.3 months) were included in the study. Any new renal scarring was more common among those with recurrent urinary tract infection (OR 4.1, 95% CI 2.0-8.5, p <0.01) after adjusting for age, sex, index urinary tract infection, duplication, bowel bladder dysfunction and antibiotic prophylaxis. Recurrent urinary tract infection associated new renal scarring occurred in 5 of 244 (2%) patients on antibiotic prophylaxis and 13 of 245 (5%) on placebo. Compared to antibiotic prophylaxis, placebo was associated with a higher risk of recurrent urinary tract infection associated new renal scarring (OR 3.1, 95% CI 1.0-8.8, p=0.04) after adjusting for age, sex, race, index urinary tract infection, bowel bladder dysfunction, duplication, hydronephrosis, vesicoureteral reflux grade and baseline renal scarring. There were no differences in scar severity at final dimercaptosuccinic acid scan (p=0.88) or change from baseline (p=0.53) between antibiotic prophylaxis and placebo. CONCLUSIONS:Recurrent urinary tract infection was associated with new renal scarring in the RIVUR trial. When limited to recurrent urinary tract infection associated new renal scarring, antibiotic prophylaxis was associated with a decreased risk of this outcome. It remains unclear why new renal scarring developed in a proportion of subjects without recurrent urinary tract infection. The results should be carefully interpreted due to the inherent limitations.

SUBMITTER: Wang HH

PROVIDER: S-EPMC7375173 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Project description:ImportanceRecurrent urinary tract infection (UTI) is a common debilitating condition in women, with limited prophylactic options. d-Mannose has shown promise in trials based in secondary care, but effectiveness in placebo-controlled studies and community settings has not been established.ObjectiveTo determine whether d-mannose taken for 6 months reduces the proportion of women with recurrent UTI experiencing a medically attended UTI.Design, setting, and participantsThis 2-group, double-blind randomized placebo-controlled trial took place across 99 primary care centers in the UK. Participants were recruited between March 28, 2019, and January 31, 2020, with 6 months of follow-up. Participants were female, 18 years or older, living in the community, and had evidence in their primary care record of consultations for at least 2 UTIs in the preceding 6 months or 3 UTIs in 12 months. Invitation to participate was made by their primary care center. A total of 7591 participants were approached, 830 responded, and 232 were ineligible or did not proceed to randomization. Statistical analysis was reported in December 2022.InterventionTwo grams daily of d-mannose powder or matched volume of placebo powder.Main outcomes and measuresThe primary outcome measure was the proportion of women experiencing at least 1 further episode of clinically suspected UTI for which they contacted ambulatory care within 6 months of study entry. Secondary outcomes included symptom duration, antibiotic use, time to next medically attended UTI, number of suspected UTIs, and UTI-related hospital admissions.ResultsOf 598 women eligible (mean [range] age, 58 [18-93] years), 303 were randomized to d-mannose (50.7%) and 295 to placebo (49.3%). Primary outcome data were available for 583 participants (97.5%). The proportion contacting ambulatory care with a clinically suspected UTI was 150 of 294 (51.0%) in the d-mannose group and 161 of 289 (55.7%) in the placebo group (risk difference, -5%; 95% CI, -13% to 3%; P = .26). Estimates were similar in per protocol analyses, imputation analyses, and preplanned subgroups. There were no statistically significant differences in any secondary outcome measures.Conclusions and relevanceIn this randomized clinical trial, daily d-mannose did not reduce the proportion of women with recurrent UTI in primary care who experienced a subsequent clinically suspected UTI. d-Mannose should not be recommended for prophylaxis in this patient group.Trial registrationisrctn.org Identifier: ISRCTN13283516.

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Why Does Prevention of Recurrent Urinary Tract Infection not Result in Less Renal Scarring? A Deeper Dive into the RIVUR Trial.

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