Supplementary Material for: Non-invasive serum LOX: a prognostic signature for fibrosis progression and renal survival in IgA nephropathy

Background: IgA nephropathy (IgAN), the most common primary glomerulonephritis, often presents with advanced renal failure and end-stage renal disease at diagnosis.Till now, there remains a lack of reliable biomarkers for effectively assessing the progression risk of IgAN. Here, we propose lysyl oxidase (LOX), a marker of collagen cross-linking, as a potential biomarker for assessing fibrosis in IgAN. Method: After evaluating the fibrosis degree by -Masson staining-, measuring LOX levels in serum and kidney tissues, and collecting clinical information, we analyzed the association between LOX and renal fibrosis. Logistic regression analysis was employed to identify significant variables, which were incorporated into a nomogram and machine learning (ML) model. Results: A total of 128 IgAN patients were enrolled in the study, of which 89 were included in the training cohort and 39 patients in the validation cohort. Serum LOX levels correlated with the area of renal fibrosis (r = 0.673, p <0.001). ROC analysis of LOX showed an AUC of 0.793 and 0.785 with optimal cut-off value of 297.59 pg/mL and 395.02 pg/mL for the prediction of mild and moderate to severe renal fibrosis, respectively. The diagnostic nomogram model for predicting renal function decline within three years incorporated traditional clinical determinants along with the Oxford MEST histological score (model 1), achieving an AUC of 0.740 (95% CI: 0.565-0.914, p < 0.05). In contrast, a model (model 2) that combined traditional clinical determinants with LOX instead of the Oxford MEST histological score demonstrated improved predictive performance, yielding an AUC of 0.806 (95% CI: 0.655-0.956, p < 0.01). Conclusions: Serum LOX has the potential to predict renal fibrosis in IgAN. When combined with traditional clinical indicators, it may enhance the prediction of IgAN prognosis.