Mechanisms of calcineurin inhibitor nephrotoxicity in chronic allograft injury

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Title: Mechanisms of calcineurin inhibitor nephrotoxicity in chronic allograft injury
Authors: Slattery, Craig
Cassidy, Hilary
Johnston, Olwyn
Ryan, Michael P.
McMorrow, Tara
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Date: 2012
Abstract: The first successful transplantation of a human kidney was performed more than 50 years ago by Murray and colleagues in 1954 between identical twins. The success of this transplantation was due to the fact that no significant rejection occurs between genetically identical twins and therefore immunosuppression was not necessary in this particular case (Merrill et al., 1956). However, solid-organ transplantation could not be considered truly successful until the 1970’s after significant technical and pharmacological advances. In particular, the discovery and development of the calcineurin inhibitors (CNIs) has made allograft transplantation routinely successful with greatly reduced risk of acute rejection. In the absence of pharmacological agents to address the primary pathological mechanisms involved, renal transplantation has now been the standard management of end stage renal failure for the past four decades (Wolfe et al., 1999). Short-term renal allograft and allograft recipient survival rates have increased significantly during the last decade largely due to improved patient monitoring. However, allograft half-life beyond 1 year post-transplant remains largely unchanged. While rates of early allograft failure have significantly reduced, late renal allograft dysfunction remains a significant problem in the transplant population (de Fijter). Chronic allograft injury (CAI) is the most prevalent cause of allograft dysfunction in the first decade after transplantation. The term CAI is used to describe deterioration of renal allograft function and structure due to immunological processes (i.e. chronic rejection) and/or a range of simultaneous nonimmunological factors such as CNI-induced nephrotoxicity, hypertension and infection. This chapter will outline the pathophysiology and etiology of CAI and the role that CNI nephrotoxicity plays in this disease process. It will also review experimental studies that have identified important molecular mechanisms involved and discuss strategies utilised to minimise the development and progression of CAI.
Funding Details: Science Foundation Ireland
Higher Education Authority
Irish Research Council for Science, Engineering and Technology
European Research Council
Health Research Board
Type of material: Book Chapter
Publisher: Intech
Copyright (published version): 2012 the authors
Keywords: Chronic allograft injuryCalcineurin inhibitor toxicity
Subject LCSH: Homografts
Immunosuppressive agents
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Language: en
Status of Item: Peer reviewed
Is part of: Sahay, Manisha (ed.). Chronic kidney disease and renal transplantation
ISBN: 978-953-51-0003-4
Appears in Collections:Conway Institute Research Collection
Biomolecular and Biomedical Science Research Collection

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