The Therapeutic Potential of CDK4/6 Inhibitors, Novel Cancer Drugs, in Kidney Diseases.

Inflammation is a crucial pathological feature in cancers and kidney diseases, playing a significant role in disease progression. Cyclin-dependent kinases CDK4 and CDK6 not only contribute to cell cycle progression but also participate in cell metabolism, immunogenicity and anti-tumor immune responses. Recently, CDK4/6 inhibitors have gained approval for investigational treatment of breast cancer and various other tumors. Kidney diseases and cancers commonly exhibit characteristic pathological features, such as the involvement of inflammatory cells and persistent chronic inflammation. Remarkably, CDK4/6 inhibitors have demonstrated impressive efficacy in treating non-cancerous conditions, including certain kidney diseases. Current studies have identified the renoprotective effect of CDK4/6 inhibitors, presenting a novel idea and potential direction for treating kidney diseases in the future. In this review, we briefly reviewed the cell cycle in mammals and the role of CDK4/6 in regulating it. We then provided an introduction to CDK4/6 inhibitors and their use in cancer treatment. Additionally, we emphasized the importance of these inhibitors in the treatment of kidney diseases. Collectively, growing evidence demonstrates that targeting CDK4 and CDK6 through CDK4/6 inhibitors might have therapeutic benefits in various cancers and kidney diseases and should be further explored in the future.

Role and mechanisms of SGLT-2 inhibitors in the treatment of diabetic kidney disease.

Diabetic kidney disease (DKD) is a chronic inflammatory condition that affects approximately 20-40% of individuals with diabetes. Sodium-glucose co-transporter 2 (SGLT-2) inhibitors, emerging as novel hypoglycemic agents, have demonstrated significant cardiorenal protective effects in patients with DKD. Initially, it was believed that the efficacy of SGLT-2 inhibitors declined as the estimated glomerular filtration rate (eGFR) decreased, which led to their preferential use in DKD patients at G1-G3 stages. However, recent findings from the DAPA-CKD and EMPA-KIDNEY studies have revealed equally beneficial cardiorenal effects of SGLT-2 inhibitors in individuals at stage G4 DKD, although the underlying mechanism behind this phenomenon remains unclear. In this comprehensive analysis, we provide a systematic review of the mechanisms and functioning of SGLT-2 inhibitors, potential renal protection mechanisms, and the therapeutic efficacy and safety of SGLT-2 inhibitors in kidney diseases, with a particular focus on stage G4 DKD. Gaining a deeper understanding of the renal protective effect of SGLT-2 inhibitors and their underlying mechanisms is highly significance for the successful utilization of these inhibitors in the treatment of diverse kidney disorders.