Introduction: Ischemia/reperfusion injury (IRI) is a major source of morbidity in renal transplantation and other surgical scenarios and is minimally treatable.  In renal transplantation, IRI contributes to poor outcomes and early graft loss. Histone deacetylases (HDACs) regulate diverse cellular processes. We have previously shown that the class I HDACs 1 and 2 have reciprocal effects on renal ischemia-reperfusion injury (IRI) with HDAC1 deletion increasing vulnerability and HDAC2 protection providing profound protection. The role of HDAC 11, a class IV HDAC, is previously uninvestigated.
Methods: Whole-body tamoxifen-inducible HDAC-11 deficient (HDAC11 KO), and tamoxifen-treated wild type (WT) male mice were also used. Mice were subjected to warm renal IRI through unilateral clamping of the renal pedicle and contralateral nephrectomy under strict temperature control.  Creatinine and BUN were examined at 24-, 48-, 72-, and 96-hours post IRI.
Results: HDAC11 KO mice exhibited protection from renal IRI compared to WT controls, with significantly decreased post-operative BUN but not Creatinine (Fig 1).
Conclusion: Deletion of HDAC11 protects mice from renal IRI.  It is a promising target for pharmacologic inhibition to develop novel therapies to treat renal injury. In addition, study of downstream targets of HDAC11 will provide further insight into mechanisms of protection and additional therapeutic targets.