Abstract 18599: Diabetes Aggravates Both Acute Kidney Injury (AKI) After Acute Myocardial Infarction and AKI After Ischemia-Reperfusion by Distinct Mechanisms

Purpose: Diabetes (DM) increases the severity of acute kidney injury (AKI), in which roles of caspase-mediated apoptosis and RIP1/RIP3-dependent necroptosis have been implicated. Here, we examined whether distinct cell death mechanisms are involved in two types of AKI, myocardial infarction (MI)-triggered cardio-renal syndrome (CRS) and renal ischemia/reperfusion (I/R). Methods and Results: We used OLETF, a rat model of type 2 DM at 25-30 weeks old, when early nephropathy is indicated by increased urinary protein without increase in serum creatinine (sCr), and its non-DM control, LETO. In the first series of experiments, to prepare a model of CRS, MI was induced by ligation of a left coronary artery for 12 hrs. Though sCr level was not increased in either OLETF or LETO after MI, immunostaining revealed that the area positive for kidney injury molecule-1, a marker of AKI, was significantly increased by 5.3 fold (P Conclusions: Apoptosis, but not necroptosis, via the TLR/TNF pathway, is involved in AKI induced by CRS in OLETF. In contrast, necroptosis, but not apoptosis, plays a major role in aggravation of I/R-induced AKI in OLETF. Two distinct cell death mechanisms play roles in DM-induced aggravation of AKI, depending on the type and/or strength of insult to cause AKI.