Novel Biomarkers as Non-Invasive Diagnostic Tools in IgA Nephropathy: A Comparative Study with Lupus Nephritis and Membranous Nephropathy.

Rationale: The diagnostic value of endothelial-associated biomarkers in IgAN and their ability to differentiate it from other kidney diseases have not yet been clarified.

Objective: This study aimed to investigate the diagnostic value of endothelial-associated biomarkers in IgAN patients.

Methods and results: This is a cross-sectional study involving 96 participants, with IgAN, LN, MN, and healthy subjects recruited in a 1:1:1:1 ratio. Seventy-five percent of the sample was used for developing a classification model, and the remaining 25% was used for constructing a validation cohort. Plasma levels of 12 endothelial-associated biomarkers were detected using multiplex immunoassay technology. Among all the biomarkers evaluated, VLA-4 and VEGFD were prioritized for distinguishing IgAN from other groups (p<0.001), with 85% classification accuracy. These two biomarkers also showed significant correlation with eGFR (VLA-4: r = - 0.291, P = 0.021; VEGFD: r = - 0.271, P = 0.031) and Gd-IgA1 (VLA-4: r = 0.403, P = 0.003; VEGFD: r = 0.412, P = 0.002). These two biomarkers also showed superior diagnostic efficacy (AUC=0.952 and 0.945) compared to Gd-IgA1 (AUC=0.736). Subgroup analysis of IgAN patients revealed clinically relevant effect sizes for the IgA and IgA/C3 ratios between high- and low-VLA-4 and VEGFD groups, with Hedges' g values of 0.962 and 0.819, respectively. The diagnostic efficacy of VLA-4 and VEGFD levels in IgAN was further validated in an independent cohort comprising 24 participants.

Conclusion: VLA-4 and VEGFD emerge as robust, non-invasive biomarkers for IgAN diagnosis and may play significant roles in the pathogenesis of IgAN.