CD38 inhibitors(Immunophage Biotech)

Diabetic kidney disease (DKD) is one of the most common microvascular complications among individuals with diabetes and has become a leading cause of end-stage renal disease (ESRD). The mechanisms underlying DKD are complex, and effective therapeutic strategies remain limited. Mitochondrial dysfunction occurs earlier than proteinuria and renal morphological changes, and is considered a key event in the progression of DKD. Mitochondrial dysfunction in diabetic kidneys involves several processes, including excessive production of mitochondrial reactive oxygen species, reduced mitochondrial biogenesis, impaired mitophagy, and disturbances in mitochondrial dynamics. Recently, mitochondria-targeted drugs, including antioxidants, CD38 inhibitors, glucose-linked transport 2 sodium inhibitor (SGLT2i), and compounds derived from traditional Chinese medicine, have shown positive effects in animal experiments or clinical trials. This review aims to highlight the role of mitochondrial quality control and dysfunction in DKD, the specific mitochondrial regulators of different renal cell types, as well as the therapeutic potential of some emerging drugs and the limitations of existing preclinical evidence, thereby identifying promising therapeutic targets and strategies for the disease.