Table 1.

Approaches to ameliorate abnormal mitochondrial function and to decrease ROS production in DKD.

Agent	Mechanism of action	In vivo studies
Bardoxolone methyl	Suppressing inflammation Inhibition of NF-κB	Reduction of eGFR decline
DPP-4 inhibitors	Increasing CREB and PGC-1α Increasing Nrf2	Decreases in albuminuria and mesangial expansion
SGLT2 inhibitors	Correcting abnormal Mfn and Opa1 Decreasing ROS	Decreases in albuminuria and renal fibrosis
Metformin	Inhibition of complex I and mGPDH Inhibition of NF-kB Activation of Pink1 and Parkin	Amelioration of renal oxidative stress and tubulointerstitial fibrosis
Imeglimin	Decreasing reverse electron transport through complex I Reducing the activity of complex II, decreasing ROS Restoring the expression of a subunit of complex III	Decreases in albuminuria and interstitial fibrosis

NF-κB, nuclear factor-kappa B; GFR, glomerular filtration rate; DPP-4, dipeptidyl peptidase-4; CREB, cAMP response element-binding protein; PGC-1a, peroxisome proliferator-activated receptor gamma coactivator 1-alpha; Nrf2, NFE-2 related factor 2; ROS, reactive oxygen species; mGPDH, mitochondrial glycerol 3-phosphate dehydrogenase.