Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
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Nephrol. Dial. Transplant. · Nov 2018
ReviewTargeting epigenetic DNA and histone modifications to treat kidney disease.
Epigenetics refers to heritable changes in gene expression patterns not caused by an altered nucleotide sequence, and includes non-coding RNAs and covalent modifications of DNA and histones. This review focuses on functional evidence for the involvement of DNA and histone epigenetic modifications in the pathogenesis of kidney disease and the potential therapeutic implications. There is evidence of activation of epigenetic regulatory mechanisms in acute kidney injury (AKI), chronic kidney disease (CKD) and the AKI-to-CKD transition of diverse aetiologies, including ischaemia-reperfusion injury, nephrotoxicity, ureteral obstruction, diabetes, glomerulonephritis and polycystic kidney disease. ⋯ Several drugs targeting epigenetic regulators are in clinical development or use, most of them for malignancy. The BET inhibitor apabetalone is in Phase 3 trials for atherosclerosis, kidney function being a secondary endpoint, but nephrotoxicity was reported for DNA and HDAC inhibitors. While research into epigenetic modulators may provide novel therapies for kidney disease, caution should be exercised based on the clinical nephrotoxicity of some drugs.