INTRODUCTION: Diabetic kidney disease (DKD) is one of the most common causes of chronic kidney disease, leading to end-stage kidney disease (ESKD), and is one of the most significant complications associated with diabetes mellitus. Furthermore, the medical costs of dialysis therapy associated with ESKD are high, and financial strain is a major problem. This review first focuses on the mechanisms of DKD progression and exacerbation, and then describes the 'DKD fantastic four,' which we advocate as the latest DKD treatment.
AREAS COVERED: In DKD, increase in the extracellular matrix of mesangial cells is attributed to transforming growth factor-β/Smad1/type 4 collagen signaling, whose effects are enhanced by angiotensin II signaling.DKD activates protein kinase C (PKC)d, leading to dephosphorylation of vascular endothelial growth factor receptor-2 and reduction of its downstream effects, thereby inducing podocyte apoptosis. PKCβ inhibits insulin receptor substrate 1/Akt/endothelial NO synthase signaling in glomerular endothelial cells.
EXPERT OPINION: Recently, sodium-glucose co-transporter 2 inhibitors have been shown to reduce the risk of progression of nephropathy. Additionally, glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptides elicit vasoactive effects, reducing the risk of DKD. Finerenone, a non-steroidal mineralocorticoid receptor antagonist, reduces the composite renal endpoint without causing severe hyperkalemia.
