Exploring molecular targets in diabetic kidney disease

Diabetic kidney disease is the leading cause of end-stage kidney disease, and it remains a major challenge. Many factors, such as glomerular hyperfiltration, oxidative stress, inflammation, hypoxia, and epigenetics, are associated with the progression of diabetic kidney disease; however, the whole mechanism is not yet completely understood. No specific treatment for diabetic kidney disease has been established, so new approaches are being explored extensively. Sodium-glucose cotransporter 2 inhibitors have shown renoprotective effects in several human clinical trials. Glucagon-like peptide 1 receptor agonists and mineralocorticoid receptor antag-onists have been reported to be effective in diabetic kidney disease, and novel therapeutic candidates are also being examined. In the TSUBAKI trial, a nuclear factor erythroid 2-related factor 2 activator, bardoxolone methyl, improved the glomerular filtration rate of diabetic kidney disease patients. Similarly, new agents that act in the oxidative stress and inflammation pathways are of major inter-est, such as pentoxifylline, apoptosis signal-regulating kinase-1 inhibitors, C-C chemokine receptor 2 inhibitors, and Janus kinase-1/2 inhibitors. Endothelin-1 receptor A antagonists and soluble guanylate cyclase stimulators are also expected to affect renal hemody-namics. Some preclinical studies suggest that hypoxia-inducible factor prolyl hydroxylase inhibitors, which influence multiple inflam-mations and oxidative stress pathways, reduce albuminuria in diabetic kidney disease. Advanced glycation end-product inhibitors and treatments related to epigenetics have also shown promise as potential diabetic kidney disease treatments in preclinical studies. The discovery of new targets could provide new therapeutic options for overcoming diabetic kidney disease.

Automated summary

Diabetic kidney disease is a major challenge and the leading cause of end-stage kidney disease. Although the exact mechanism is not completely understood, several factors including hyperfiltration, oxidative stress, inflammation, hypoxia, and epigenetics are associated with its progression. Studies have shown that sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and mineralocorticoid receptor antagonists have renoprotective effects, while other potential therapeutic candidates are being explored. New targets, such as oxidative stress and inflammation pathways, are of great interest, and various drugs are under investigation. The discovery of new therapeutic options could provide alternative treatments for diabetic kidney disease.