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Calcineurin inhibitors and immunosuppression – a tale of two isoforms

Published online by Cambridge University Press:  04 July 2012

Clintoria R. Williams  and
Jennifer L. Gooch
Clintoria R. Williams
Affiliation:
Department of Medicine, Division of Nephrology, Emory University School of Medicine, Atlanta, GA, USA
Jennifer L. Gooch*
Affiliation:
Department of Medicine, Division of Nephrology, Emory University School of Medicine, Atlanta, GA, USA Atlanta Veterans Administration Medical Center, Decatur, GA, USA
*
*Corresponding author: Jennifer L. Gooch, Medicine/Nephrology, Emory University School of Medicine, 101 Woodruff Circle, WMB 338, Atlanta, GA 30322, USA. E-mail: jgooch@emory.edu
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Abstract

Organ transplantation is the state of the art for treating end-stage organ failure. Over 25 000 organ transplants are performed in the USA each year. Survival rates following transplantation are now approaching 90% for 1 year and 75% for 5 years. Central to this success was the introduction of drugs that suppress the immune system and prevent rejection. The most commonly used class of immunosuppressing drugs are calcineurin inhibitors (CNIs). Calcineurin is a ubiquitous enzyme that is important for T-cell function. With more people taking CNIs for longer and longer periods of time the consequences of calcineurin inhibition on other organ systems – particularly the kidney – have become a growing concern. Virtually all people who take a CNI will develop some degree of kidney toxicity and up to 10% will progress to kidney failure. In the past 15 years, research into calcineurin action has identified distinct actions of the two main isoforms of the catalytic subunit of the enzyme. The α-isoform is required for kidney function whereas the β-isoform has a predominant role in the immune system. This review will discuss the current state of knowledge about calcineurin isoforms and how these new insights may reshape post-transplant immunosuppression.

Type
Review Article
Information
Expert Reviews in Molecular Medicine , Volume 14 , March 2012 , e14
Copyright
Copyright © Cambridge University Press 2012

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Further reading, resources and contacts

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http://www.UNOS.org.Google Scholar