Urinary miR-221-3p and miR-324-5p in combination with albuminuria as a promising model for non-invasive diagnosis of pediatric celiac disease

Celiac disease (CD) is a chronic autoimmune enteropathy triggered by gluten ingestion that can cause intestinal damage and extra-intestinal complications, including renal involvement in children. MicroRNAs (miRNAs) are small, stable, non-coding RNAs detectable in body fluids, and urinary miRNAs are particularly promising biomarkers due to their non-invasive collection and ability to reflect kidney function. While circulating miRNAs have been proposed as diagnostic markers of CD and indicators of adherence to a gluten-free diet (GFD), their role in monitoring renal alterations in pediatric patients remains unclear. Conventional measures, such as albuminuria, detect kidney damage but lack specificity for disease-related changes. Therefore, we aimed at exploring the possibility that urinary miRNAs coupled to albuminuria could be used to diagnose both CD and the presence of renal alterations. We analyzed urinary miRNA profiles in pediatric CD patients at diagnosis, on GFD, and in healthy controls. We found that urinary miR-221-3p and miR-324-5p and albuminuria are significantly dysregulated in children with CD compared to GFD and controls, identifying them as candidate biomarkers for diagnostic applications. Under GFD, their expression normalized supporting their potential role not only in monitoring renal recovery but also in objectively assessing dietary adherence. These findings highlight urinary miRNAs in combination with albuminuria as clinically relevant, non-invasive predictors for a non-invasive diagnosis of pediatric CD. More broadly, they suggest that urinary miRNA profiling could serve as a promising translational method to improve early detection, patient stratification, and longitudinal management across pediatric autoimmune disorders once fully validated in future larger cohorts.