Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Kidney Function in Advanced Chronic Kidney Disease

Sodium-glucose cotransporter 2 (SGLT2) inhibitors, originally developed as oral antihyperglycemic agents for managing type 2 diabetes, have quickly gained recognition for their broad therapeutic benefits beyond glycemic control. Since their clinical introduction in 2012, SGLT2 inhibitors have demonstrated significant renoprotective and cardioprotective effects, reshaping treatment approaches in nephrology and cardiology.

Although these drugs have shown great promise, major clinical trials have typically excluded patients with advanced chronic kidney disease (CKD) (eGFR < 20 mL/min/1.73m²), those already on dialysis, and kidney transplant recipients-populations at the highest risk of kidney failure, cardiovascular complications, and mortality. This exclusion has left a critical gap in understanding the full potential of SGLT2 inhibitors in the most vulnerable patients. As such, current KDIGO guidelines have not recommended initiating SGLT2 inhibitors in patients with eGFR < 20 mL/min/1.73m².

CKD is a global health crisis, affecting approximately 10% of adults worldwide, with prevalence rising in Egypt, where 13% of adults are affected, especially in underserved rural areas. By 2040, CKD is projected to become the fifth leading cause of death worldwide.

For patients with kidney failure, the primary treatment options are renal replacement therapies like dialysis or transplantation. However, due to the scarcity of donor kidneys and the frequent presence of comorbidities in older populations, transplantation is often unfeasible. Consequently, most end-stage kidney disease (ESKD) patients rely on dialysis, a therapy that significantly lowers quality of life and increases mortality risk.

Preserving kidney function is a critical goal in CKD management, which is closely linked to better patient outcome. Incremental dialysis, a strategy aimed at preserving residual kidney function (RKF), shows promise but lacks robust clinical validation. Increasing evidence suggests that SGLT2 inhibitors, even in patients with advanced CKD, may offer significant reno- and cardioprotective benefits, reinforcing the need for further research into their efficacy in this population.