Machine learning applied to digital pathology has been increasingly used to assess kidney function and diagnose the underlying cause of chronic kidney disease (CKD). We developed a novel computational framework, clustering-based spatial analysis (CluSA), that leverages unsupervised learning to learn spatial relationships between local visual patterns in kidney tissue. This framework minimizes the need for time-consuming and impractical expert annotations. 107,471 histopathology images obtained from 172 biopsy cores were used in the clustering and in the deep learning model. To incorporate spatial information over the clustered image patterns on the biopsy sample, we spatially encoded clustered patterns with colors and performed spatial analysis through graph neural network. A random forest classifier with various groups of features were used to predict CKD. For predicting eGFR at the biopsy, we achieved a sensitivity of 0.97, specificity of 0.90, and accuracy of 0.95. AUC was 0.96. For predicting eGFR changes in one-year, we achieved a sensitivity of 0.83, specificity of 0.85, and accuracy of 0.84. AUC was 0.85. This study presents the first spatial analysis based on unsupervised machine learning algorithms. Without expert annotation, CluSA framework can not only accurately classify and predict the degree of kidney function at the biopsy and in one year, but also identify novel predictors of kidney function and renal prognosis.
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