Integrative Analysis on the Urinary Proteome of Diabetic Kidney Disease, with an Emphasis on Extracellular Matrix Proteins

One of the key pathological features of Diabetic Kidney Disease (DKD) progression is the accumulation of extracellular matrix (ECM) proteins in kidneys, leading to thickening of the glomerular and tubular basement membranes, subsequently resulting in mesangial expansion, sclerosis, and tubulointerstitial fibrosis. Given the high prevalence of DKD among both T2DM and T1DM patients, as well as the complexity of its underlying molecular mechanisms, this study provides a comparative analysis of published urinary proteomics datasets in DKD (n = 4). By integrating these data with published tissue proteomics (n = 2) and published transcriptomics datasets (n = 5), the study further aims to link urinary findings to tissue pathophysiology. Through integrative proteomic and transcriptomic analysis, DKD was associated with distinct alterations in the urinary proteome, particularly involving proteins related to ECM turnover. Using multiple validation datasets, several upregulated proteins with potential biological significance were identified, including annexins, collagens, cathepsins, and glycoproteins. Overall, our findings underscore the critical role of ECM remodeling in DKD progression and further validation could open new avenues for biomarker development and targeted therapy in early stages of DKD.