medwireNews: Recurrent urinary tract infections (UTIs) are associated with decreasing estimated glomerular filtration rate (eGFR) in children with vesicoureteral reflux (VUR), US researchers report.
David Hains and co-investigators from Indiana University School of Medicine in Indianapolis, suggest that “[a]ntibiotic prophylaxis, even if discordant, may limit breakthrough UTI severity or subsequent AKI [acute kidney injury] and subsequently preserve eGFR.”
Their findings are based on an individual-level analysis of 188 children aged 6 months or older who participated in the RIVUR trial and had eGFR measured both before and after treatment. The trial assessed the impact of long-term, once-daily, oral antimicrobial prophylaxis with trimethoprim/sulfamethoxazole at a trimethoprim dose of 3 mg/kg on recurrent UTI rates and kidney scarring in children with VUR.
The researchers report in JAMA Pediatrics that, overall, mean eGFR increased by 9.5 mL/min per 1.73 m2 during the 24-month study, but the change in eGFR varied according to the number of UTIs a patient experienced and whether they received antibiotic prophylaxis or placebo.
For example, eGFR fell by a mean 1.9 mL/min per 1.73 m2 from baseline to 24 months in participants who experienced more than one UTI during the study but increased by 10.4 mL/min per 1.73 m2 among those who had one or no UTIs, regardless of treatment assignment.
When only considering participants in the placebo arm, the corresponding changes were a fall of 5.9 mL/min per 1.73 m2 versus an increase of 13.9 mL/min per 1.73 m2.
Having more than one febrile UTI during the study was associated with a mean eGFR reduction of 4.0 mL/min per 1.73 m2 in the full cohort, and 13.9 mL/min per 1.73 m2 in the placebo arm. For those with one or no reported febrile UTIs, mean eGFR increased by a respective 10.2 and 13.3 mL/min per 1.73 m2.
However, when Hains and colleagues adjusted the data for age, eGFR at enrollment, and baseline bowel and bladder dysfunction, they found that that the difference in eGFR change between participants with more than one UTI and those with one or no UTIs was only significant for patients with febrile UTIs.
In this case, the adjusted change in eGFR was –16.7 mL/min per 1.73 m2 with more than one versus one or no febrile UTIs in the overall cohort and –22.3 mL/min per 1.73 m2 in the placebo group.
Of note, the adjusted change in eGFR did not differ significantly according to the number of UTIs among participants treated with antibiotic prophylaxis.
The investigators also observed a decrease in eGFR for each subsequent lifetime UTI in the placebo group but say that “small subgroups limited power to detect a dose-response relationship in a statistically significant manner.”
Hains et al acknowledge that “RIVUR was neither designed nor powered to evaluate eGFR change; therefore, our findings are solely hypothesis generating.”
And they conclude: “Further studies are needed to determine whether eGFR changes occur in a larger cohort of children with UTI.”
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