Impact of Diabetes on Renal Ischemia-reperfusion Injury in a Non-human Primate Model

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Abstract

Clinically, acute kidney injury (AKI) episodes in diabetes mellitus (DM) patients are associated with a cumulative risk for developing stage 4 chronic kidney disease. However, the underlying mechanism of AKI susceptibility in DM patients remains unclear. Here, we tested whether DM monkeys were more sensitive to AKI than non-DM monkeys and found that renal ischemia-reperfusion injury (IRI) induced more severe AKI in DM monkeys. We also tested the efficacy of using human bone marrow-derived mesenchymal stem cells (hBM-MSCs) to ameliorate AKI in DM monkeys. In our mortality rate and histologic findings, the severity of AKI in DM monkeys was higher than that in normal monkeys. In the blood of DM monkeys, tumor necrosis factor (TNF)–αlevels 6 hours after IRI were higher than in the blood of normal monkeys. This phenomenon was inhibited when 5 x 106 cell/kg of hBM-MSCs were injected into DM monkeys after IRI. Renal IRI also induced remote organ injury, according to liver enzyme levels and lung tissue histologic findings obtained during necropsy. In this large animal model, we confirmed that DM monkeys are more susceptible to AKI than normal monkeys and that IRI induced remote organ injury. MSC infusion has the potential to ameliorate AKI in DM monkeys by suppressing TNF–α secretion. IRI modeling for DM monkeys should be modified.

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