What a Modern Physician Should Know About microRNAs in the Diagnosis and Treatment of Diabetic Kidney Disease

Abstract

Diabetic kidney disease (DKD) remains the leading cause of end-stage kidney disease (ESKD) globally. Despite advances in our understanding of its pathophysiology, current therapies are often insufficient to stop its progression. In recent years, microRNAs (miRNAs)-small, non-coding RNA molecules involved in post-transcriptional gene regulation-have emerged as critical modulators of key pathogenic mechanisms in DKD, including fibrosis, inflammation, oxidative stress, and apoptosis. Numerous studies have identified specific miRNAs that either exacerbate or mitigate renal injury in DKD. Among them, miR-21, miR-192, miR-155, and miR-34a are associated with disease progression, while miR-126-3p, miR-29, miR-146a, and miR-215 demonstrate protective effects. These molecules are also detectable in plasma, urine, and renal tissue, making them attractive candidates for diagnostic and prognostic biomarkers. Advances in therapeutic technologies such as antagomiRs, mimics, locked nucleic acids, and nanoparticle-based delivery systems have opened new possibilities for targeting miRNAs in DKD. Additionally, conventional drugs, including SGLT2 inhibitors, metformin, and GLP-1 receptor agonists, as well as dietary compounds like polyphenols and sulforaphane, may exert nephroprotective effects by modulating miRNA expression. Recent evidence also highlights the role of gut microbiota in regulating miRNA activity, linking metabolic and immune pathways relevant to DKD progression. Further research is needed to define stage-specific miRNA signatures, improve delivery systems, and develop personalized therapeutic approaches. Modulation of miRNA expression represents a promising strategy to slow DKD progression and improve patient outcomes.

Keywords: biomarkers; diabetic kidney disease; gene regulation; microRNA; therapy.

Figure 1

Pathogenic miRNAs in DKD. Schematic representation of selected miRNAs (e.g., miR-21, miR-192, miR-155) that contribute to DKD progression by promoting renal fibrosis, inflammation, podocyte loss, apoptosis, and oxidative stress. Each miRNA regulates specific signaling pathways, including TGF-β/Smad3, NF-κB, p53, and others, which collectively contribute to the deterioration of kidney function. Abbreviations: miRNA—microRNA; DKD—diabetic kidney disease; TGF-β—transforming growth factor beta; NF-κB—nuclear factor kappa B; PTEN—phosphatase and tensin homolog; MCP-1—monocyte chemoattractant protein-1; TNF-α—tumor necrosis factor alpha; ROS—reactive oxygen species; WT1—Wilms tumor 1; NOX4—NADPH oxidase 4; SIRT1—sirtuin 1. ↑ indicates upregulation or activation; ↓ indicates downregulation or inhibition.

Figure 2

Protective miRNAs in DKD. Overview of selected miRNAs (e.g., miR-29, miR-126-3p, miR-146a, miR-215) that exert renoprotective effects in DKD. These miRNAs reduce inflammation, oxidative stress, fibrosis, and apoptosis through the regulation of signaling pathways such as TGF-β/Smad, NF-κB, VEGF, and PI3K/Akt, thereby preserving kidney structure and function. Abbreviations: miRNA—microRNA; DKD—diabetic kidney disease; TGF-β—transforming growth factor beta; NF-κB—nuclear factor kappa B; ROS—reactive oxygen species; VEGF—vascular endothelial growth factor; NOX4—NADPH oxidase 4; AMPK—AMP-activated protein kinase; mTOR—mechanistic target of rapamycin; JNK—c-Jun N-terminal kinase; TRAF6—TNF receptor-associated factor 6; IRAK1—interleukin-1 receptor-associated kinase 1; IL-6—interleukin-6; TNF-α—tumor necrosis factor alpha; CTGF—connective tissue growth factor; PI3K—phosphoinositide 3-kinase; Akt—protein kinase B; Bcl-2—B-cell lymphoma 2; Bax—Bcl-2-associated X protein. ↑ indicates upregulation or activation; ↓ indicates downregulation or inhibition.

Figure 3

Sources and functions of miRNAs in DKD. Diagram illustrating the biological sources of circulating miRNAs, which can be detected in blood, urine, and renal biopsy specimens. Owing to their stability in body fluids and specific expression profiles, miRNAs have potential as diagnostic and prognostic biomarkers in DKD. They regulate key pathological processes such as inflammation and fibrosis, making them relevant tools for disease monitoring and risk stratification. Abbreviations: miRNA—microRNA; DKD—diabetic kidney disease.