As phosphorylation of ERK1/2 and activation of Bcl-2 are important pathways in CKD and MI/R injuries, our data indicate that linagliptin protects the myocardium and renal tubules from CKD with cardiac ischemia-reperfusion induced apoptosis via modulation of the ERK1/2 and Bcl-2 signaling pathways. Here, MAPK3 is linked to chronic kidney disease.