For the thousands of patients who receive kidney transplants in the United States each year, preventing organ rejection without compromising other aspects of health requires a delicate balance of medications. Immunosuppresive drugs that protect transplanted organs can also cause serious side effects, including compromising patients' immunity to infection, cancer, and other threats. Finding the best combination and dosage of drugs has often proved difficult for physicians.
A new multi-year study has now shown that using tacrolimus (TAC) and mycophenolate mofetil (MMF) in combination provided the best long-term benefits and the least amount of side effects after a kidney transplant. The results, which come from the longest randomized study to date that has analyzed transplant drugs, provide valuable guidance to physicians who care for for kidney transplant patients. The study, conducted by Giselle Guerra, MD, and colleagues at the University of Miami, appears in an upcoming issue of the Journal of the American Society Nephrology (JASN), a publication of the American Society of Nephrology.
To compare therapies, Dr. Guerra studied 150 kidney transplant recipients who received one of three common immunosuppressive treatment regimens: tacrolimus + MMF, tacrolimus + sirolimus, or cyclosporine + sirolimus. Tacrolimus and cyclosporine are in a class of drugs called calcineurin inhibitors; they can prevent early organ rejection but can be toxic to the kidneys. Sirolimus and MMF do not damage the kidneys. Patients often receive low doses of calcineurin inhibitors plus sirolimus or MMF in order to gain the most benefit without serious risk to their kidneys. All patients in the study also received another immunosuppressive drug called daclizumab shortly after transplantation, as well as steroids long term; they were followed for an average of eight years after transplantation.
Among the major findings:Survival of transplanted organs was similar in all groups of patients.
Patients taking tacrolimus + MMF also had better kidney function during the first 36 months.
Patients taking tacrolimus + MMF or cyclosporine + sirolimus were less likely to die with a functioning transplant (12% and 4% respectively), compared to those treated with tacrolimus + sirolimus (26%).
Patients who took sirolimus were more likely to develop viral infections, discontinue treatment, and need cholesterol-lowering medications, compared to patients who were not taking sirolimus.
Taken together, these results suggest that transplant patients do better over the long term with tacrolimus + MMF than with either tacrolimus + sirolimus or cyclosporine + sirolimus. "We have been able to prove that the use of low-dose tacrolimus and MMF is safe and provides excellent outcomes over time to renal transplant patients," said Dr. Guerra.
Study co-authors include Gaetano Ciancio, MD, Jeffrey Gaynor, PhD, Alberto Zarak, Randolph Brown, Lois Hanson, DO, Junichiro Sageshima, MD, David Roth, MD, Linda Chen, MD, Warren Kupin, MD, Lissett Tueros, Phillip Ruiz, MD, PhD, Alan Livingstone, MD, and George Burke III, MD (University of Miami).
Disclosures: The authors of this manuscript have conflicts of interest to disclose as described by the Journal of the American Society of Nephrology. Astellas Pharma US, Inc. provided partial salary support (with a grant of $75,000) for the completion of this study to the Kidney and Kidney/Pancreas Transplant Program at the University of Miami. Representatives of Astellas had no direct involvement in this study, and none of the co-authors have any financial interest in Astellas.
The article, entitled "Randomized Trial of Immunosuppressive Regimens in Renal Transplantation," will appear online at http://jasn.asnjournals.org/ 10.1681/ASN.2011010006
The content of this article does not reflect the views or opinions of The American Society of Nephrology (ASN). Responsibility for the information and views expressed therein lies entirely with the author(s). ASN does not offer medical advice. All content in ASN publications is for informational purposes only, and is not intended to cover all possible uses, directions, precautions, drug interactions, or adverse effects. This content should not be used during a medical emergency or for the diagnosis or treatment of any medical condition. Please consult your doctor or other qualified health care provider if you have any questions about a medical condition, or before taking any drug, changing your diet or commencing or discontinuing any course of treatment. Do not ignore or delay obtaining professional medical advice because of information accessed through ASN. Call 911 or your doctor for all medical emergencies.
Founded in 1966, and with more than 12,000 members, the American Society of Nephrology (ASN) leads the fight against kidney disease by educating health professionals, sharing new knowledge, advancing research, and advocating the highest quality care for patients.
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