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Mechanisms of calcineurin inhibitor nephrotoxicity in chronic allograft injury


Slattery, Craig; Cassidy, Hilary; Johnston, Olwyn; Ryan, Michael P.; McMorrow, Tara;

Institution: Intech
Subject Keywords: Chronic allograft injury; Calcineurin inhibitor toxicity; Homografts; Immunosuppressive agents; Kidneys--Transplantation; Transplantation, Homologous--adverse effects; Immunosuppressive Agents--toxicity; Kidney Transplantation;
Topic: Chronic Conditions
Catalogue: Research and Evaluation
Type: Report
Region: Republic of Ireland

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.



Suggested citation:

Slattery, Craig; Cassidy, Hilary; Johnston, Olwyn; Ryan, Michael P.; McMorrow, Tara; . () Mechanisms of calcineurin inhibitor nephrotoxicity in chronic allograft injury [Online]. Available from: [Accessed: 20th September 2019].


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