Review on the Gut‐Kidney Axis Mechanism and Therapeutic Strategies in Diabetic Nephropathy

Diabetic nephropathy (DN), a major microvascular complication of diabetes, has a high global incidence and heavy disease burden. It tends to progress to end-stage renal disease, and existing therapeutic methods are insufficient to completely halt disease progression. The gut-kidney axis is a functional unit enabling bidirectional communication between the intestine and kidneys via microbiota, metabolites, and immune factors. Its dysfunction-characterised by intestinal flora imbalance, reduced short-chain fatty acids, accumulation of uraemic toxins, and activation of signalling pathways such as Toll-like receptor 4/nuclear factor-kappa B-serves as a core driver of DN pathological progression. This review systematically analyzes key microbiota-metabolite signalling pathways and regulatory mechanisms in the DN gut-kidney axis and summarises intervention strategies based on this axis (including probiotic/prebiotic-mediated flora regulation, multi-target intervention with traditional Chinese medicine [TCM] compounds, precise pathway blocking by targeted drugs like sodium-dependent glucose transporters two inhibitors, and high-fibre dietary management) along with clinical evidence grading. It also identifies translational bottlenecks, such as low probiotic colonisation rates and unclear active components of TCM. Finally, it prospects future research directions, including clinical translation of gut-kidney axis markers and neuroendocrine regulatory mechanisms, providing a theoretical basis for precise diagnosis and treatment of DN and facilitating improved patient prognosis.