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Related Experiment Videos

Maintenance immunosuppression: new agents and persistent dilemmas.

J M Gonin1

  • 1Division of Nephrology and Hypertension, Georgetown University Medical Center, Washington, DC 20007, USA. goninj@gunet.georgetown.edu

Advances in Renal Replacement Therapy
|April 27, 2000
PubMed
Summary

New immunosuppressants like tacrolimus and sirolimus reduce early rejection after kidney transplants but long-term survival benefits and safety profiles require further study. Steroid withdrawal success varies among different immunosuppression regimens.

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Area of Science:

  • Nephrology
  • Immunology
  • Pharmacology

Background:

  • Cyclosporine, approved in 1983, remains a benchmark for immunosuppression in renal transplantation.
  • Mycophenolate mofetil, tacrolimus, and sirolimus are newer agents for maintenance immunosuppression.
  • These agents effectively reduce early acute allograft rejection.

Purpose of the Study:

  • To evaluate the impact of newer immunosuppressive agents on intermediate and long-term renal allograft survival.
  • To assess the safety profiles and cardiovascular implications of these drugs.
  • To explore the efficacy of steroid-withdrawal strategies in conjunction with various immunosuppression regimens.

Main Methods:

  • Review of clinical trial data on immunosuppressive agents in renal transplant recipients.

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  • Analysis of safety profiles, including cardiovascular risk factors like hypertension and hyperlipidemia.
  • Examination of graft survival trends in specific high-risk populations, such as African-Americans and pancreas-kidney recipients.
  • Assessment of outcomes from steroid-withdrawal and steroid-avoidance clinical trials.

    • Main Results:

    • While mycophenolate mofetil, tacrolimus, and sirolimus decrease early acute rejection, their impact on intermediate and long-term graft survival is not definitively established.
    • Tacrolimus may offer cardiovascular benefits, whereas sirolimus is associated with severe hyperlipidemia, with unknown long-term consequences.
    • Tacrolimus and mycophenolate mofetil show promise for improved graft survival in pancreas-kidney recipients and a positive trend in African-American recipients.
    • Steroid withdrawal is achievable in approximately 50% of patients on cyclosporine-based regimens, with potentially higher success rates using newer agents or formulations.

    Conclusions:

    • The long-term efficacy and safety of newer immunosuppressants require further investigation, particularly concerning cardiovascular health and specific patient populations.
    • Steroid-withdrawal strategies may be enhanced with newer immunosuppressive agents, but more research is needed.
    • Continued research is essential to optimize immunosuppression and improve long-term outcomes in renal transplant recipients.