The Role of Non-Coding RNAs in the Pathogenesis and Progression of Diabetic Kidney Disease

Diabetic kidney disease (DKD) remains a leading cause of end-stage renal disease worldwide, with current therapies often failing to halt its progression due to an incomplete understanding of intrinsic renal molecular mechanisms. This review highlights the pivotal role of non-coding RNAs (ncRNAs)-including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs)-as central regulators in the pathogenesis and progression of DKD. We systematically examine how the diabetic milieu dysregulates specific ncRNA profiles in renal cells, driving core pathological processes such as metabolic dysfunction, inflammation, fibrosis, and podocyte injury. Furthermore, we explore the emerging roles of exosomal ncRNAs in intercellular communication and their potential as non-invasive liquid biopsy biomarkers for early diagnosis and disease monitoring. Finally, we discuss the translational prospects of targeting ncRNAs through innovative therapeutic strategies, such as antisense oligonucleotides and miRNA mimics, while addressing the challenges of tissue-specific delivery and clinical implementation. Understanding ncRNA networks offers a refined, systems-level perspective on DKD and opens new avenues for precision diagnostics and targeted interventions aimed at modifying the disease course.