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Right Combination of Immunosuppressive Drugs May Lead to Less Organ Rejection and Long-term Benefits

Preventing organ rejection for kidney transplants without compromising other aspects of health requires a delicate balance of medications.  Finding this balance and the correct dosage of drugs has been difficult for physicians.  For example, immunosuppressive drugs that protect transplanted organs can also cause serious side effects, including compromising patients’ immunity to infection, cancer, and other threats.

A new multi-year study, conducted by Giselle Guerra, MD, and colleagues at the University of Miami has shown that using tacrolimus (TAC) and mycophenolate mofetil (MMF) in combination provided the vest long-term benefits and the least amount of side effects after a kidney transplant.  This was the longest randomized study to date that has analyzed transplant drugs.  The results provide valuable guidance to physicians who treat kidney transplant patients.  The study appears in an upcoming issue of the Journal of the American Society Nephrology (JASN), a publication of the American Society of Nephrology.

Guerra studied 150 kidney transplant recipients who received one of three common immunosuppressive treatment regimens: tacrolimus + MMF, tacrolimus + sirolimus, or cydosporine + sirolimus.  Tacrolimus and cydosporine are in a class of drugs called calcineurin inhibitors; they can prevent early organ reject but can be toxic to the kidneys.  Sirolimus and MMF do not damage the kidneys.  Often, patients receive low doses of calcineurin inhibitors plus sirolimus or MMF in order to gain the most benefit without serious risk to their kidneys.  The patients in the study also received another immunosuppressive drug, dadizumab, shortly after transplantation, and long term steroids.  All patients were followed for an average of eight years after transplantation.

The research team found that survival of transplanted organs was similar in all groups of patients.  Significantly fewer patients treated with tacrolimus + MMF (12%) experienced acute rejection, compared to those given tracrolimus + sirolimus (30%) or cyclosporine + sirolimus (28%).  Patients taking tacrolimus + MMF also had better kidney function during the first three years.  Patients given 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 were given sirolimus were more likely to develop viral infections, discontinue treatment, and need cholesterol-lowering medications, compared to patients not taking sirolimus.  In conclusion, the results suggest that transplant patients do better long term with tacrolimus + MMG than with either tacrolimus + sirolimus or cyclosporine + sirolimus.

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