ObjectivesTo develop and validate an ultrasomics-based machine-learning (ML) model for non-invasive assessment of interstitial fibrosis and tubular atrophy (IF/TA) in patients with IgA nephropathy (IgAN).Materials and methodsIn this multi-center retrospective study, 471 patients with primary IgA nephropathy from four institutions were included (training, n = 275; internal testing, n = 69; external testing, n = 127; respectively). The least absolute shrinkage and selection operator logistic regression with tenfold cross-validation was used to identify the most relevant features. The ML models were constructed based on ultrasomics. The Shapley Additive Explanation (SHAP) was used to explore the interpretability of the models. Logistic regression analysis was employed to combine ultrasomics, clinical data, and ultrasound imaging characteristics, creating a comprehensive model. A receiver operating characteristic curve, calibration, decision curve, and clinical impact curve were used to evaluate prediction performance.ResultsTo differentiate between mild and moderate-to-severe IF/TA, three prediction models were developed: the Rad_SVM_Model, Clinic_LR_Model, and Rad_Clinic_Model. The area under curves of these three models were 0.861, 0.884, and 0.913 in the training cohort, and 0.760, 0.860, and 0.894 in the internal validation cohort, as well as 0.794, 0.865, and 0.904 in the external validation cohort. SHAP identified the contribution of radiomics features. Difference analysis showed that there were significant differences between radiomics features and fibrosis. The comprehensive model was superior to that of individual indicators and performed well.ConclusionsWe developed and validated a model that combined ultrasomics, clinical data, and clinical ultrasonic characteristics based on ML to assess the extent of fibrosis in IgAN.Key PointsQuestionCurrently, there is a lack of a comprehensive ultrasomics-based machine-learning model for non-invasive assessment of the extent of Immunoglobulin A nephropathy (IgAN) fibrosis.FindingsWe have developed and validated a robust and interpretable machine-learning model based on ultrasomics for assessing the degree of fibrosis in IgAN.Clinical relevanceThe machine-learning model developed in this study has significant interpretable clinical relevance. The ultrasomics-based comprehensive model had the potential for non-invasive assessment of fibrosis in IgAN, which helped evaluate disease progress.Key PointsQuestionCurrently, there is a lack of a comprehensive ultrasomics-based machine-learning model for non-invasive assessment of the extent of Immunoglobulin A nephropathy (IgAN) fibrosis.FindingsWe have developed and validated a robust and interpretable machine-learning model based on ultrasomics for assessing the degree of fibrosis in IgAN.Clinical relevanceThe machine-learning model developed in this study has significant interpretable clinical relevance. The ultrasomics-based comprehensive model had the potential for non-invasive assessment of fibrosis in IgAN, which helped evaluate disease progress.Key PointsQuestionCurrently, there is a lack of a comprehensive ultrasomics-based machine-learning model for non-invasive assessment of the extent of Immunoglobulin A nephropathy (IgAN) fibrosis.FindingsWe have developed and validated a robust and interpretable machine-learning model based on ultrasomics for assessing the degree of fibrosis in IgAN.Clinical relevanceThe machine-learning model developed in this study has significant interpretable clinical relevance. The ultrasomics-based comprehensive model had the potential for non-invasive assessment of fibrosis in IgAN, which helped evaluate disease progress.