A Systems Nephrology Approach to Diabetic Kidney Disease Research and Practice

Background. Diagnosis and staging of diabetic kidney disease (DKD) via the serial assessment of routine laboratory indices lacks the granularity required to resolve the heterogenous disease mechanisms driving progression in the individual patient. A systems nephrology approach may help to resolve mechanisms underlying this clinically apparent heterogeneity, paving a way for targeted treatment of DKD.Summary. Given the limited access to kidney tissue in routine clinical care of patients with DKD, data derived from renal tissue in preclinical model systems, including animal and in vitro models, can play a central role in the development a targeted systems-based approach to DKD. Multi-centre prospective cohort studies, including the Kidney Medicine Precision Project (KPMP) and the European Nephrectomy Biobank (ENBiBA) project, will improve access to human diabetic kidney tissue for research purposes. Integration of diverse data domains from such initiatives including clinical phenotypic data, renal and retinal imaging biomarkers, histopathological and ultrastructural data, and an array of molecular omics (transcriptomics, proteomics, etc.) alongside multi-dimensional data from preclinical modelling offers exciting opportunities to unravel individual-level mechanisms underlying progressive DKD. The application of machine and deep learning approaches may particularly enhance insights derived from imaging and histopathological/ultrastructural data domains.Key Messages. Integration of data from multiple model systems (in vitro, animal models, and patients) and from diverse domains (clinical phenotypic, imaging, histopathological/ultrastructural, and molecular omics) offers potential to create a precision medicine approach to DKD care wherein the right treatments are offered to the right patients at the right time.