A new analysis of the RIVUR trial indicates that antibiotic prophylaxis may help protect the kidneys of children with vesicoureteral reflux who experience febrile urinary tract infections (UTIs). The study, presented at the American Society of Nephrology Kidney Week, suggests that UTIs can negatively impact kidney function at a microscopic level, potentially leading to long-lasting consequences if not properly managed.
Impact of Febrile UTIs on Kidney Function
The research, led by David S. Hains, MD, MBA, of the Indiana University School of Medicine, examined data from 188 children with vesicoureteral reflux, a common congenital anomaly. The findings revealed that children who experienced more than one febrile UTI during the 2-year study period had an average eGFR (estimated glomerular filtration rate) that was -16.7 mL/min/1.73 m2 (95% CI -32.1 to -1.3) lower than those with one or fewer UTIs, according to an adjusted model. This decline in eGFR, a measure of kidney function, was published simultaneously in a JAMA Pediatrics research letter.
Protective Effect of Antibiotic Prophylaxis
Interestingly, the eGFR decline was only observed in children who were not receiving antibiotic prophylaxis during the study. Children on continuous antibiotic prophylaxis showed a nonsignificant decline of -8.0 mL/min/1.73 m2 (95% CI -30.6 to 14.5), while those on placebo experienced a substantial eGFR reduction of -22.3 mL/min/1.73 m2 (95% CI -43.5 to -1.0) associated with febrile UTIs.
"We were pleasantly surprised by our findings," Hains told MedPage Today. He noted that clinical observations in children with vesicoureteral reflux often do not align with clinical trial results, suggesting that previous studies may have focused on the wrong outcomes.
Reevaluating the Standard of Care
The original 2014 RIVUR trial primarily focused on UTI recurrence prevention and kidney scarring as secondary outcomes. While trimethoprim-sulfamethoxazole prophylaxis reduced the risk of UTI recurrence by 50% (HR 0.50, 95% CI 0.34 to 0.74) compared to placebo, the occurrence of renal scarring did not differ significantly between the prophylaxis and placebo groups (11.9% and 10.2%, respectively).
Hains argues that the current study demonstrates that UTIs affect kidney function at a microscopic level, which may not be detected by traditional DMSA scans that monitor macroscopic changes. He suggests that GFR may be a more appropriate measure for assessing kidney health in children with vesicoureteral reflux.
Implications for Clinical Practice
The findings also raise questions about the utility of continuous antibiotic prophylaxis in protecting kidney function. Hains suggests that pediatricians may have underestimated the value of antibiotic prophylaxis in recent years and that it is important to continuously question established standards of care.
He also emphasized that radiologic testing may not provide a complete picture of kidney function and that pediatric nephrologists should be involved in the early longitudinal care of children with vesicoureteral reflux to monitor and intervene when kidney function changes.
Study Details and Limitations
The current analysis included 89 RIVUR participants who received antibiotic prophylaxis and 99 children on placebo, all of whom had available data on entry and exit serum creatinine measurements. Participants were ages 6 months and older and had grade I to IV vesicoureteral reflux diagnosed after a first or second febrile or symptomatic UTI. The eGFR change was calculated as the difference between the 2-year exit eGFR and the enrollment eGFR, adjusted for factors such as eGFR at enrollment, bowel and bladder dysfunction, and age.
Overall, the median eGFR change was a nonsignificant -2.6 (95% CI -11.4 to 6.3) for each additional lifetime UTI among study participants. Hains acknowledged that the RIVUR trial was not specifically designed or powered to evaluate eGFR change, calling for additional, larger studies to further investigate the impact of UTIs on kidney function in children.
He concluded that advancements in creatinine measurement and GFR estimation over the past 15 years warrant a reevaluation of established practices and a closer look at the long-term effects of UTIs on kidney health.
