REN and chronic kidney disease: Despite the present therapeutic options for controlling blood glucose and blood pressure, including angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), direct renin inhibitors (DRIs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors, kidney damage and kidney function deterioration still inevitably occur in a majority of patients with DN and chronic kidney disease (CKD), which consequently progresses to ESRD 5-9.