Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. C URRENT O PINION Novel therapeutic strategies for renal graft preservation and their potential impact on the future of clinical transplantation Smriti Juriasingani a,b , Masoud Akbari a,b , Patrick Luke a,b,c,d , and Alp Sener a,b,c,d Purpose of review The current review aims to examine recent evidence about improvements, therapeutics and novel approaches for renal graft preservation along with presenting a pragmatic outlook on their potential for clinical translation. Recent findings Modifying established cold preservation methods (4 8C) with oxygenation, gene therapies and gasotransmitters such as hydrogen sulfide has been shown to improve renal graft outcomes with minimum modifications to current protocols. These strategies have also shown promise in the context of normothermic preservation (34–37 8C), which circumvents the damage caused by cold preservation. Although normothermic machine perfusion (NMP) is being evaluated in clinical trials, it is limited by high cost, the use of blood and the lack of standardized protocols. Recent studies confirmed that preservation at subnormothermic temperatures (20 8C) is effective with approved preservation solutions and, in conjunction with exogenous hydrogen sulfide therapy, this approach may expedite a static preservation alternative to NMP. Summary Progress has been made in investigating improvements and alternatives to cold preservation. Promising therapeutic strategies have also been studied in the context of cold, subnormothermic and normothermic preservation. Further research is needed to optimize clinical renal graft preservation. Keywords gene therapy, hydrogen sulfide, kidney preservation, normothermic, subnormothermic INTRODUCTION The prevalence of end-stage renal disease (ESRD) has steadily increased over the past few decades. Currently, there are two treatment options for ESRD patients: hemodialysis or renal transplantation. Transplantation is the superior treatment option because it reduces long-term mortality by 48–82% compared with dialysis [1]. Transplantation also improves quality of life, reduces the risk of cardio- vascular events and diminishes the long-term economic burden compared with hemodialysis [2,3]. However, the demand for transplantable kidneys outweighs the supply. As per the Organ Procurement and Transplant Network, 92 685 patients were on the kidney transplant waitlist in the United States as of December 2017 [4]. Due to the shortage of organs, renal grafts obtained from deceased donors are being transplanted more fre- quently [4]. However, deceased donor kidneys have been shown to have higher rates of delayed graft function (DGF) and poorer long-term survival than living donor kidneys [5,6 & ]. Kidneys obtained from donors after cardiac death (DCD) are of particular interest because, in addition to being used more frequently, they repre- sent a potential avenue of increasing the pool of transplantable kidneys. In most jurisdictions, they a Department of Microbiology & Immunology, Schulich School of Medi- cine & Dentistry, University of Western Ontario, b Matthew Mailing Centre for Translational Transplant Studies, University Hospital, London Health Sciences Centre, c Department of Surgery, Schulich School of Medicine & Dentistry, St. Joseph’s Healthcare London and d Multi Organ Transplant Program, University Hospital, London Health Sciences Centre, London, Ontario, Canada Correspondence to Alp Sener, MD, PhD, FRCSC, University Hospital, C4-208, London Health Sciences Centre, 339 Windermere Road, London, ON, Canada N6A 5A5. Tel: +1 519 685 8500x33352; e-mail: alp.sener@lhsc.on.ca Curr Opin Organ Transplant 2019, 24:385–390 DOI:10.1097/MOT.0000000000000660 1087-2418 Copyright ß 2019 Wolters Kluwer Health, Inc. All rights reserved. www.co-transplantation.com REVIEW