Evaluation Of The Protective Role Of Empagliflozin In Inflammation-Triggered Kidney Disease In Preclinical Settings

Abstract

Inflammation has a critical part in the occurrence of diabetes mellitus (DM) and diabetic nephropathy (DN). DN, if not adequately controlled, is the principal basis for progression to end-stage renal disease. DN, existing with albuminuria, glomerulosclerosis, and decreased glomerular filtration rate, is driven by complex pathophysiological mechanisms, including inflammation as a center of causative mechanisms. In DN, high glucose levels promote renal inflammation via NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) transcription factors activation. NF-κB after phosphorylation further triggers transcriptional up-regulation of NLRP3 (NLR family pyrin domain containing 3), upregulates inflammatory cytokines, and stimulates the inflammatory cascade leading to renal injury. Despite current therapies for DM, the progression of DN remains a challenge. Empagliflozin (EMP) is a sodium-glucose cotransporter 2 inhibitor. EMP has shown promising renoprotective effects beyond glycemic control in DN. Preclinical studies in animal models have demonstrated renoprotective effects of EMP beyond glycemic control, especially through its antiinflammatory properties. However, the role of EMP in the protection of DN via modulation of inflammatory pathways is still not clear. This review highlights the current evidence from preclinical animal studies that explore the effect of EMP in protecting against diabetic-associated kidney disease (DKD) through the inhibition of inflammatory pathways.