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The impact of calcineurin inhibitors on graft survival
1Department of Internal Medicine, University of Manitoba, Winnipeg, MB R3A 1R9, Canada. drush@exchange.hsc.mb.ca
Abstract:
The discovery of the first calcineurin inhibitor (CNI), cyclosporine, represents a watershed event in the history of immunosuppression, as it was the first drug shown to reversibly inhibit T-lymphocyte function, therefore allowing for one of the major breakthroughs in modern medicine, that of organ transplantation. Calcineurin inhibitors remain the most effective and widely used immunosuppressive agents in organ transplantation today. The 2010 OPTN/SRTR Annual Report showed that 96% of renal transplant recipients were on CNI at the time of discharge from hospital. The prolonged use of CNI, however, may result in renal toxicity, renal dysfunction and eventual renal failure in both recipients of renal and other solid organ transplants, as well as in patients treated with these agents for autoimmune diseases. This brief review, while acknowledging that CNI toxicity does indeed exist, will focus on the successful use of CNI in renal transplant recipients, highlighting recent observations that provide alternative explanations for some of the adverse outcomes that have been attributed to CNI nephrotoxicity in the past.
Insights
Calcineurin inhibitors (CNIs) are vital immunosuppressants in organ transplantation. While CNI toxicity is acknowledged, this review explores their successful use in renal transplants, offering new perspectives on adverse outcomes.
Area of Science:
- Immunology
- Nephrology
- Pharmacology
Background:
- Calcineurin inhibitors (CNIs), like cyclosporine, revolutionized organ transplantation by inhibiting T-lymphocyte function.
- CNIs are the most effective and widely used immunosuppressants in organ transplantation, with 96% of renal transplant recipients using them at discharge.
- Prolonged CNI use can lead to renal toxicity, dysfunction, and failure in transplant recipients and patients with autoimmune diseases.
Purpose of the Study:
- To review the successful application of CNIs in renal transplant recipients.
- To provide alternative explanations for adverse outcomes previously attributed to CNI nephrotoxicity.
- To acknowledge the existence of CNI toxicity while focusing on successful therapeutic use.
Main Methods:
- Literature review of studies on calcineurin inhibitors in renal transplantation.
- Analysis of recent observations regarding CNI use and patient outcomes.
- Synthesis of evidence to re-evaluate attributed adverse effects of CNIs.
Main Results:
- CNIs remain critical for successful organ transplantation, particularly in renal recipients.
- Recent findings suggest alternative causes for some adverse renal outcomes previously linked solely to CNIs.
- The review acknowledges CNI toxicity but emphasizes successful management and alternative explanations for complications.
Conclusions:
- Calcineurin inhibitors are indispensable in modern immunosuppression for organ transplantation.
- Further research is needed to differentiate CNI-induced nephrotoxicity from other causes of renal dysfunction in transplant patients.
- Successful management strategies and a nuanced understanding of CNI effects are crucial for long-term graft survival.
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