Inflammatory mechanisms in diabetic nephropathy: emerging insights and targeted therapeutics

Background: Diabetic kidney disease (DKD) remains a leading cause of end-stage renal disease (ESRD) worldwide. Understanding of DKD pathogenesis has undergone a pivotal shift, moving beyond traditional metabolic and hemodynamic paradigms to underscore the critical role of chronic inflammation. Objective: This review aims to systematically delineate recent advances in the inflammatory mechanisms of DKD and to discuss their translational implications. It will focus on emerging diagnostic biomarkers and novel inflammation-targeted therapeutic strategies. Main content: This review portrays the complex interplay of emerging inflammatory mechanisms in DKD, encompassing inflammatory pathway activation, cellular senescence, impaired podocyte autophagy, the gut microbiota-kidney axis, and regulation by non-coding RNAs (ncRNAs). Meanwhile, a novel diagnostic paradigm powered by omics technologies and artificial intelligence (AI) is described, highlighting the associated biomarkers. Lastly, the therapeutic landscape, focusing on agents with proven renal benefits, including sodium-glucose cotransporter 2 (SGLT2) inhibitors, non-steroidal mineralocorticoid receptor antagonists (ns-MRAs), and glucagon-like peptide-1 receptor agonists (GLP-1RAs) is reviewed, with evaluating the promise of natural products as multi-target interventions. Conclusion: Inflammation in DKD is driven by an intricate network of local and systemic factors. A multifaceted approach which prioritizes the integration of multi-omics data for inflammatory subtyping, deciphering inter-organ communication, and developing combined therapies that leverage conventional drugs, targeted agents, and natural compounds should be adopted to advance the management of DKD.