Is uromodulin a reliable biomarker in pediatric vesicoureteral reflux? An exploratory pilot study

Vesicoureteral reflux (VUR) is associated with recurrent febrile urinary tract infections (FUTIs) and renal scarring in children. Uromodulin (UMOD), one of the most abundant urinary proteins, has been proposed as a protective factor against UTIs and a marker of tubular function. Whether urinary UMOD (uUMOD) concentrations differ between children with VUR with and without renal scars remains unexplored.

This was an exploratory, hypothesis-generating pilot study. We enrolled 42 children with VUR, at least one documented FUTI, normal eGFR, and no other urinary tract malformation, along with 17 age- and sex-matched healthy controls. uUMOD concentration (µg/ml) was measured in first-morning spot urine by ELISA. Children with renal scars on DMSA scintigraphy were classified as Group A (n = 22); those without scars as Group B (n = 20). The uUMOD/urinary creatinine ratio (uUMOD/uCre, expressed as mg/g) was used as the primary creatinine-corrected biomarker endpoint to adjust for urinary dilution. No formal a priori power calculation was feasible given the absence of prior pediatric data in this specific setting; sample size was determined by convenience sampling.

Absolute uUMOD concentrations were significantly lower in children with VUR compared to controls (p = 0.005), and lowest in Group A. However, the uUMOD/uCre ratio did not differ significantly among the three groups (Group A: 29.0 mg/g; Group B: 38.5 mg/g; controls: 36.5 mg/g; p = NS). Multivariate analysis confirmed strong collinearity between uUMOD and urinary creatinine (p<0.0001): when both were included in the regression model, only uCre retained independent significance (p = 0.01), while uUMOD did not (p = 0.18). No significant association was found between uUMOD/uCre and renal scarring, FUTI frequency, or VUR grade.

In children with VUR, the reduction in absolute uUMOD most likely reflects impaired tubular concentrating capacity rather than an independent downregulation of uromodulin secretion. This conclusion is inferred from the strong collinearity pattern and should be confirmed in future studies including direct measures of urinary concentrating ability (osmolality, specific gravity). Spot uUMOD should not be used as a standalone biomarker for renal scar risk stratification in VUR. Future prospective studies should adopt creatinine-corrected measurements or timed urine collections as primary endpoints, with adequate sample sizes, to properly evaluate uromodulin as a clinical biomarker in this population.