Interpretable Multiple-Instance Learning of Glomerular Pathomics and Subtype Ratios for eGFR Classification

Tianyu Shi, Yuechen Yang, Leiyue Zhao, Daniel Reisenbüchler, Jing Jin +5

Chronic kidney disease is characterized by structural alterations in renal tissue and progressive loss of kidney function. While glomerular subtype ratios provide a compact and clinically meaningful summary of glomerular composition, representing pathomic information using whole-slide image (WSI)-level mean values diminishes glomerulus-level heterogeneity and the contribution of less prevalent patterns. In this proof-of-concept study, we investigated whether modeling individual glomeruli using multiple-instance learning (MIL) could provide complementary information to conventional subtype ratios for estimated glomerular filtration rate (eGFR) classification. We analyzed 162 kidney-biopsy WSIs from 162 patients, categorizing renal function as eGFR < 60 or >= 60 mL/min/1.73 m^2. Quantitative size, shape, intensity, and texture features were extracted from segmented glomeruli, representing each patient as a bag of glomerular instances. An attention-based MIL model was trained to aggregate these heterogeneous pathomic profiles. We evaluated subtype ratios, pathomics, and their combination using ABMIL, with a mean-pooled multilayer perceptron baseline. In five-fold cross-validation,…