Abstract
KEY POINTS: Lack of human kidney tissue availability and access has hindered molecular understanding of human diabetic kidney disease processes and disease heterogeneity. Preclinical validation of diabetic kidney disease targets using data from large, human kidney samples should reduce poor translatability to clinical trials. The Network for Pancreatic Organ donors with Diabetes-Kidney cohort is validated and available for use by the research community. BACKGROUND: The Network for Pancreatic Organ Donors with Diabetes-Kidney (nPOD-K) project was initiated to assess the feasibility of using kidneys from organ donors to enhance understanding of diabetic kidney disease (DKD) progression. METHODS: Traditional and digital pathology approaches were used to characterize the nPOD-K cohort. Periodic acid–Schiff- and hematoxylin and eosin-stained sections were used to manually examine and score each nPOD-K case. Brightfield and fluorescently labeled whole slide images of nPOD-K sections were used to train, validate, and test deep learning compartment segmentation and machine learning image analysis tools within Visiopharm software. These digital pathology tools were subsequently used to evaluate kidney cell-specific markers and pathological indicators. RESULTS: Digital quantitation of mesangial expansion, tubular atrophy, kidney injury molecule-1 expression, cellular infiltration, and fibrosis index aligned with histological DKD classification, as defined by pathologists' review. Histological quantification confirmed loss of podocyte, endothelial, and tubular markers, correlating with DKD progression. Altered expression patterns of prominin-1, protein-tyrosine phosphatase receptor type O, and coronin 2B were validated, in agreement with reported literature. CONCLUSIONS: The nPOD-K cohort provides a unique open resource opportunity to not only validate putative drug targets, but also better understand DKD pathophysiology. A broad range of pathogenesis can be visualized in each case, providing a simulated timeline of DKD progression. We conclude that organ donor-derived tissues serve as high-quality samples, provide a comprehensive view of tissue pathology, and address the need for human kidney tissues available for research.