Inflammatory mechanisms in diabetic nephropathy: emerging insights and targeted therapeutics

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.

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.

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.

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.