A Narrative Review of Diabetic Kidney Disease: Previous and Current Evidence-Based Therapeutic Approaches

Diabetic kidney disease (DKD) is one of the most important diabetic complications. DKD is also the most common cause of chronic kidney disease (CKD) and end-stage renal disease. This review focused on potential therapeutic drugs for which there is established evidence of treatment for DKD. The earliest evidence for DKD treatment was established with renin-angiotensin system (RAS) inhibitors; however, their efficacy was partial. Recently, the sodium-glucose co-transporter 2 (SGLT2) inhibitors, including empagliflozin (EMPA-REG Outcome), canagliflozin (CREDENCE trial), and dapagliflozin (DAPA-CKD), demonstrated a significant and clinically relevant reduction in the risks of albuminuria and progression of nephropathy, doubling of serum creatinine levels, and initiation of renal replacement therapy. Additionally, incretin-based therapeutic agents, such as glucagon-like peptide 1, liraglutide (LEADER), and dipeptidyl peptidase 4 inhibitors, linagliptin (CARMERINA) have elicited vasotropic actions, suggesting a potential for reducing the risk of DKD. Until recently, mineralocorticoid receptor antagonists (MRAs) have not been suitable for DKD treatment because of their adverse effect of hyperkalemia. In contrast, finerenone, a non-steroidal MRA, significantly reduced renal composite endpoint without severe hyperkalemia that would force its discontinuation (FIDELIO-DKD). Thus, the mainstay treatments of DKD are RAS inhibitors, SGLT2 inhibitors, incretin-based therapeutic agents, and non-steroidal MRA, or in other words, the DKD "fantastic four".