Recurrent UTIs Could Damage Kidneys, Even Without Apparent Scarring

David Hains, MD
Credit: Riley's Childrens Health

An analysis of the RIVUR trial suggests could induce declines in estimated glomerular filtration rate (eGFR) among children with vescicoureteral reflux (VUR) and recurrent urinary tract infections (UTIs).

Although the trial was able to identify subsequent kidney scarring on dimercaptosuccinic acid (DMSA) among patients with VUR and recurrent UTI, the latest data suggests the absence of kidney scarring may not be indicative of the absence of kidney damage.^1,2

“Kidney scarring detected by DMSA scan may represent a visual late manifestation of UTI-associated kidney injury,” wrote investigators.¹ “Decreasing eGFR likely represents clinically relevant damage the DMSA scan cannot accurately detect, similar to the way a computed tomographic scan is limited in detecting cognitive decline.”

Published in the New England Journal of Medicine in June 2014, the Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) trial was a multicenter, randomized, placebo-controlled trial of 607 children with VUR diagnosed after a first or second febrile or symptomatic UTI. The 2-year trial was designed to assess the efficacy of trimethoprim-sulfamethoxazole prophylaxis in preventing recurrences, with an interest in evaluating kidney scarring as a secondary outcome.¹

The trial concluded use of antimicrobial prophylaxis among children with VUR after UTI was associated with a substantially reduced risk of recurrence, particularly in subgroups whose index infection was febrile and with baseline bladder and bowel dysfunction, but did not reduce the risk of kidney scarring.²

For the current study, which was presented at the American Society of Nephrology’s Kidney Week 2024, a team led by David S. Hains, MD, MBA, of the Division of Pediatric Nephrology and Hypertension at Indiana University School of Medicine, and colleagues sought to assess individual-level changes in eGFR among patients included in the trial to more fully understand the impact on kidney function. For the purpose of analysis, investigators planned to estimate eGFR change using 2-year exit eGFR minus enrollment eGFR for patients with both entry and exit eGFR, with plans to leverage multivariable linear regression analysis to adjust for age, enrollment eGFR, and baseline bowel and bladder dysfunction.¹

From the trial, investigators identified a cohort of 188 patients with entry and exit eGFR. Of these, 89 received prophylaxis and 99 received placebo therapy. The overall mean change in eGFR from entry to exit was 9.5 (SD, 24.1) mL/min/1.73m2.¹

Results indicated children with more than 1 study UTI had a mean eGFR change 12.3mL/min/1.73m2 lower than those with 1 or fewer UTIs (eGFR change, −1.9 [95% CI, 13.7 to 9.9] vs 10.4 [95% CI, 6.8 to 14.0] mL/min/1.73m2; P = .03). Additionally, children with more than 1 UTI receiving placebo therapy had a mean eGFR change 19.9 mL/ min/1.73m2 lower than those with 1 or fewer UTIs (eGFR change, −5.9 [95% CI,−17.8 to 5.9] vs 13.9 [95% CI, 8.4 to 19.5] mL/min/1.73m2; P = .01). Further, results suggested children with more than 1 febrile UTI receiving placebo had a lower net change in eGFR by 27.1 mL/min/1.73m2 relative to their counterparts with 1 or less.¹

In multivariable analysis, having more than 1 febrile UTI during the study period was associated with a significant change in eGFR in both the overall and placebo groups in the overall cohort and placebo group (adjusted between-group difference, −16.7 [95% CI, −32.1 to−1.3] and−22.3 [95% CI, −43.5 to −1.0] mL/min/1.73 m2). Investigators highlighted no significant differences observed based on receipt of antibiotic prophylaxis.¹

“Further studies are needed to determine whether eGFR changes occur in a larger cohort of children with UTI,” investigators concluded.¹

References:

Hains DS, Starr MC, Schwaderer AL. Glomerular Filtration Rate Changes Following UTI in Children With Vesicoureteral Reflux. JAMA Pediatr. Published online October 24, 2024. doi:10.1001/jamapediatrics.2024.4546

RIVUR Trial Investigators, Hoberman A, Greenfield SP, et al. Antimicrobial prophylaxis for children with vesicoureteral reflux. N Engl J Med. 2014;370(25):2367-2376. doi:10.1056/NEJMoa1401811