Improved Immunosuppression in African Americans
Joseph B. Africa, MD
FORT LAUDERDALE—Steroid-free immunosuppression in African-American (AA) renal transplant recipients using alemtuzumab induction with low-dose tacrolimus and mycophenolate (FK/MMF) maintenance may be done safely and successfully, according to researchers.
The rates of acute rejection and graft survival were comparable to those observed in non-AA renal transplant patients who received the same regimen. Study findings were presented here at the American Society of Transplant Surgeons 10th Annual State of the Art Winter Symposium.
Researchers at Washington Hospital Center in Washington, D.C., compared their experience with an alemtuzumab induction/steroid-free maintenance regimen in 190 AA and 91 non-AA recipients.
All patients received their transplants between January 1, 2004 and December 31, 2006 and were followed through January 2009. The study excluded patients who received a simultaneous pancreas and kidney transplant or a pancreas transplant after a kidney transplant. It also excluded patients who received induction therapy other than alemtuzumab or maintenance therapy with regimens other than FK/MMF.
All subjects had received alemtuzumab prior to transplantation. MMF (1 gram twice a day) was started on the day of transplant and then tapered to 500 mg twice a day by the second week.
Within 72 hours of transplantation, all renal recipients were started on tacrolimus with a target trough of 4-8 ng/dL. Intravenous methylprednisolone (500 mg) was started on day of transplant and then tapered to 250 mg, 125 mg postoperative day 2 and 3. Patients who received kidneys from deceased donors or who were at high risk for delayed graft function (DGF) had their prednisone tapered and then discontinued by day 14. The MMF dose was 1.0 to 1.5 g a day for both groups throughout all time points.
The acute rejection rates at one year were 15% in the AA patients and 14% in the non-AA patients. At three years, the rates were 28% and 23%, respectively. At three years, graft survival rates were similar in the two groups (87% for AA patients, 93% for non-AA patients).
Patient survival rates also were comparable (92% and 98%). The rates of infection that required hospitalization were 24% and 21% for AA and non-AA patients at three years. At three years, steroid-free rates were 78% in the AA patients and 84% in the non-AA patients. All between-group differences were not statistically significant.
“Right now, what limits our success in renal transplantation are long-term outcomes and we think a major part of it is the way we handle immunosuppression,” said transplant surgeon Joseph Africa, MD, one of the investigators. “So, by minimizing immunosuppression we think eventually this will lead to longer graft and patient survival. We need longer follow-up and we are still following these patients.”
The newer more potent induction drug regimens may offer improved outcomes due to the fact that they allow minimization of immunosuppression, Dr. Africa said. “African Americans are considered high risk, and it appears that taking this approach is better,” he told Renal & Urology News. “The costs with this approach are cheaper as well.”
Study co-investigator Jimmy Light, MD, Director of Transplant Services, said this study is important because it shows that potent lymphocyte-depletion with proper induction agents can effectively minimize immunosuppression in African Americans.
“The potency of the induction agent is substantially better and simpler than it used to be,” Dr. Light said. “It is also just one expense. We think that the minimal rejection rates and minimal exposure to otherwise nephrotoxic agents will lead to better long-term graft survival.”