Sodium-glucose cotransporter 2 inhibitors: a novel approach to prevent the transition from acute kidney injury to chronic kidney disease.

Purpose of review: Acute kidney injury (AKI) often progresses to chronic kidney disease (CKD), yet standardized clinical guidelines for managing this transition remain lacking. Recent studies suggest that sodium-glucose cotransporter 2 inhibitors (SGLT2i) or flozins improve AKI outcomes. Studies on patients living with diabetes post-AKI show flozins reduce mortality, CKD progression, and recurrent AKI, highlighting their potential in mitigating maladaptive kidney repair. We discuss recent preclinical evidence supporting a role of SGLT2i during AKI repair and subsequent CKD.

Recent findings: AKI is characterized by endothelial and tubular injury, hypoperfusion, metabolic dysfunction, inflammation, and cell death. SGLT2i restore renal hemodynamics, mitochondrial dysfunction, and reduce oxidative stress, improving recovery following AKI. Additionally, SGLT2i mitigate cell death by counteracting apoptosis and ferroptosis while reducing inflammation through suppression of pro-inflammatory cytokines and inflammasome activation. Beyond AKI, flozins exhibit long-term antifibrotic effects, reducing extracellular matrix deposition even after treatment discontinuation. Preclinical studies demonstrate a sustained protective effect on kidney integrity months after short-term treatment.

Summary: These inhibitors hold promise for broad nephroprotection, with robust biological rationale in maladaptive repair. Further research is needed to optimize their use and establish clinical guidelines for AKI management in both diabetic and nondiabetic populations.