Machine learning in renal pathology.

Introduction: When assessing kidney biopsies, pathologists use light microscopy, immunofluorescence, and electron microscopy to describe and diagnose glomerular lesions and diseases. These methods can be laborious, costly, fraught with inter-observer variability, and can have delays in turn-around time. Thus, computational approaches can be designed as screening and/or diagnostic tools, potentially relieving pathologist time, healthcare resources, while also having the ability to identify novel biomarkers, including subvisual features. Methods: Here, we implement our recently published biomarker feature extraction (BFE) model along with 3 pre-trained deep learning models (VGG16, VGG19, and InceptionV3) to diagnose 3 glomerular diseases using PAS-stained digital pathology images alone. The BFE model extracts a panel of 233 explainable features related to underlying pathology, which are subsequently narrowed down to 10 morphological and microstructural texture features for classification with a linear discriminant analysis machine learning classifier. 45 patient renal biopsies (371 glomeruli) from minimal change disease (MCD), membranous nephropathy (MN), and thin-basement membrane nephropathy (TBMN) were split into training/validation and held out sets. For the 3 deep learningmodels, data augmentation and Grad-CAM were used for better performance and interpretability. Results: The BFE model showed glomerular validation accuracy of 67.6% and testing accuracy of 76.8%. All deep learning approaches had higher validation accuracies (most for VGG16 at 78.5%) but lower testing accuracies. The highest testing accuracy at the glomerular level was VGG16 at 71.9%, while at the patient-level was InceptionV3 at 73.3%. Discussion: The results highlight the potential of both traditional machine learning and deep learning-based approaches for kidney biopsy evaluation.