LAUSR

Ischemic acute kidney injury (AKI) is predominantly mediated by the innate inflammatory response to damage-associated molecular patterns released during the reperfusion phase of the ischemic event. In this study, we show that pre-emptive IgM infusions to increase binding of natural IgM (nIgM) anti-leucocyte autoantibodies (IgM-ALA), inhibit this inflammatory response and prevent AKI in mice. Similarly, AKI was prevented by pre-emptively infusing Bregs, induced ex vivo by pre-treating pan-B cells with nIgM. Harnessing such a physiologic mechanism to inhibit inflammation and prevent ischemia-induced AKI can have translational potential in humans. For example, one can pre-emptively infuse IgM or ex vivo induced Bregs in patients who have a high risk of developing ischemia-induced AKI, especially the subset of these patients with low levels of IgM-ALA or regulatory T cells (Tregs).