New Insights into the Role of Mitochondrial Dysfunction in Diabetic Kidney Disease in the Omics Era

Abstract

Abstract Diabetic kidney disease (DKD) is a major microvascular complication of diabetes and the leading cause of end-stage renal disease worldwide. Accumulating evidence identifies mitochondrial dysfunction as a central driver of DKD progression by linking metabolic reprogramming, oxidative stress, and inflammatory responses. Recent advances in spatial omics, genomics, transcriptomics, proteomics, metabolomics, and microbiome analyses have enabled the characterization of cell-specific and dynamic alterations in mitochondrial function and their interactions with the renal microenvironment. Integrative analyses across these molecular layers have revealed key mechanisms involving mitochondrial quality control, metabolic reprogramming, and inflammatory signaling, while identifying potential biomarkers and therapeutic targets. Furthermore, these approaches have provided mechanistic insights into the renoprotective effects of conventional therapies and bioactive compounds from traditional Chinese medicine. This integrative review synthesizes current evidence to clarify the role of mitochondrial dysfunction in DKD pathogenesis and discusses emerging opportunities for biomarker discovery and precision therapeutics.