GFR Changes Following Urinary Tract Infection (UTI) in Children with Vesicoureteral Reflux (VUR)

Background: The Randomized Intervention for Children with Vesicoureteral Reflux (RIVUR) trial examined whether continuous antibiotic prophylaxis (CAP) prevented recurrent UTIs in children with VUR. Kidney scarring by dimercaptosuccinic acid (DMSA) scan was a secondary outcome. CAP did not prevent kidney scarring at 2-year study conclusion. Intra-patient changes in kidney function were not assessed. We determined eGFR changes in RIVUR participants with vs without UTI. Methods: We calculated eGFR via Schwartz formula in RIVUR participants aged >6 months with entry and exit serum creatinine measurements available. Exposure: study and lifetime UTIs. Outcome: ΔeGFR, calculated as 2-year exit eGFR minus entry eGFR. We also performed multivariable linear regression. Results: Children with >1 study UTI had a mean ΔeGFR 12.3 lower than those with <1 UTI (P=.03). Children with >1 symptomatic UTI receiving placebo had a mean ΔeGFR 19.9 lower than those with <1 UTI (P=.01). Children with >1 febrile UTI receiving placebo had a lower net ΔeGFR by 27.1.vs. those with <1 UTI (P=.02). In multivariable analysis, the association between >1 study febrile UTI and ΔeGFR remained after adjustments in the overall cohort and placebo group. No difference was seen between among those treated with CAP. While no differences existed in any groups with a single study UTI, this does not account for individuals that had multiple UTIs at entry. Thus, we examined lifetime UTIs and found those that had >1 lifetime UTI had lower net ΔeGFR (Table). Finally, ΔeGFR was not associated with new DMSA scar formation during the study. Conclusion: Multiple UTIs may have a detrimental effect on kidney function. CAP may preserve eGFR. Our findings indicate that recurrent febrile UTIs are associated with a decrease in eGFR of up to 27 mL/min/1.732. DMSA scans do not reflect clinically relevant changes in kidney function.