We propose that MRB, administered 24 h after the ischemic injury that leads to AKI, reduces inflammation and promotes efficient tissue repair that avoids the AKI to CKD transition. These data highlight a therapeutic window to preclude CKD development after AKI.

ABSTRACT:Epigenetic modifications have emerged as a new, important contributor to gene expression regulation in both normal and pathophysiological conditions. Epigenetics have been studied in many diseases and conditions such as acute kidney injury (AKI), a syndrome with a high prevalence that carries a poor prognosis with increased morbidity and mortality. In addition, it has recently been shown that AKI increases the risk for the development of chronic kidney disease (CKD). The specific molecular mechanisms by which AKI increases the risk of CKD and end stage renal disease (ESRD) remain unknown, although there is new evidence supporting a role of epigenetic changes. The most studied epigenetic regulations in AKI are chromatin compaction, DNA methylation, and histone acetylation/deacetylation. These modifications predominantly increase the production of proinflammatory and profibrotic cytokines such as: monocyte chemoattractant protein-1 (MCP-1), complement protein 3 (C3), transforming growth factor β (TGF-β) that have been shown for perpetuating inflammation, promoting epithelial-to-mesenchymal transition (EMT) and ultimately causing renal fibrosis. A review of epigenetic mechanisms, the pathophysiology of AKI and recent studies that implicate epigenetic modifications in AKI and in the transition to CKD are discussed below.