TRANSPLANT IMMUNOLOGY: REJECTION, TOLERANCE AND HISTOCOMPATIBILITY: Edited by Valeria R. MasEpigenetic modifications and the development of kidney graft fibrosisRousselle, Thomasa; Bardhi, Elissaa; Maluf, Daniel G.a,b; Mas, Valeria R.cAuthor Information aSurgical Sciences Division, Department of Surgery bProgram in Transplantation cDivision of Transplant, Department of Surgery, School of Medicine, University of Maryland, Baltimore, Maryland, USA Correspondence to Valeria R. Mas, MS, PhD, FAST, Professor of Surgery, Chief, Surgical Sciences Division, Department of Surgery, School of Medicine, University of Maryland, HSF3 Building, W Baltimore Street, 7th Floor, Room 71, Baltimore, MD 21201, USA. Tel: +1 901 448 3071; fax: +1 901 448 3071; e-mail: [email protected] Current Opinion in Organ Transplantation: February 2021 - Volume 26 - Issue 1 - p 1-9 doi: 10.1097/MOT.0000000000000839 Buy Metrics Abstract Purpose of review To outline recent discoveries in epigenetic regulatory mechanisms that have potential implications in the development of renal fibrosis following kidney transplantation. Recent findings The characterization of renal fibrosis following kidney transplantation has shown TGFβ/Smad signaling to play a major role in the progression to chronic allograft dysfunction. The onset of unregulated proinflammatory pathways are only exacerbated by the decline in regulatory mechanisms lost with progressive patient age and comorbidities such as hypertension and diabetes. However, significant developments in the recognition of epigenetic regulatory markers upstream of aberrant TGFβ-signaling has significant clinical potential to provide therapeutic targets for the treatment of renal fibrosis. In addition, discoveries in extracellular vesicles and the characterization of their cargo has laid new framework for the potential to evaluate patient outcomes independent of invasive biopsies. Summary The current review summarizes the main findings in epigenetic machinery specific to the development of renal fibrosis and highlights therapeutic options that have significant potential to translate into clinical practice. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.