新试验性药物可在移植手术后保护肾脏

The experimental drug belatacept can prevent graft rejection（移植排斥） in kidney transplant recipients while better preserving kidney function when compared with standard immunosuppressive（免抑制疫力的，抑制免疫力的） drugs, data from two international phase III clinical trials show. The results are published in the March issue of the American Journal of Transplantation.

The senior author of the paper describing BENEFIT (Belatacept Evaluation of Nephroprotection and Efficacy as First-line Immunosuppression Trial) is Christian P. Larsen, MD, DPhil, director of the Emory Transplant Center and chair of the department of surgery at Emory University School of Medicine. The lead author is Flavio Vincenti, MD, professor of medicine (nephrology肾脏学) at University of California, San Francisco.

Thomas C. Pearson, MD, DPhil, professor of surgery at Emory and co-director of the kidney/pancreas（胰腺） transplant program at Emory Transplant Center, is a co-author on a companion paper describing belatacept's performance on "extended criteria" kidney transplants (Kidneys from donors that are older or have other factors associated with shorter graft survival).

The drugs most transplant patients now rely on to inhibit their immune systems and prevent graft rejection have serious side effects. The class of drugs known as calcineurin（磷酸酶） inhibitors（抑制因子） (cyclosporine环孢霉素 and tacrolimus他克莫司 , for example) can damage the kidneys and lead to high blood pressure and diabetes.

The data from the BENEFIT trial, which tracked 666 kidney transplants at 100 sites around the world, shows that patients taking belatacept had similar graft survival rates to those taking cyclosporine, while maintaining higher kidney function and lower blood pressure and cholesterol（胆固醇） . In addition, instead of requiring patients to take pills twice every day, in the case of calcineurin inhibitors, belatacept can be given every few weeks.

Trial data and side effects:

The BENEFIT trial, which was sponsored by Bristol Myers Squibb, compared three regimens（养生法，生活规则） : a more intensive and a less intensive course of belatacept treatment and a standard cyclosporine course.

All patients received a temporary course of an anti-T cell antibody called basiliximab（巴利昔单抗） and the standard transplant drugs mycophenolate mofetil（霉酚酸酯） and corticosteroids.

After one year, the proportion of patients with impaired kidney function (defined through glomerular血管小球的 filtration rate滤水率) was 55 percent for more intensive and 54 percent for less intensive, compared to 78 percent for cyclosporine. Patients' blood pressure, cholesterol and blood sugar profiles were also more favorable with belatacept.

More patients experienced acute rejection -- a temporary flare-up of the immune system against the donated kidney -- under belatacept (22 percent for more intensive, 17 percent for less) compared to 7 percent with cyclosporine. However, in most cases the acute rejection was successfully treated with drugs and did not lead to graft failure.

With belatacept, there was a higher incidence of a serious complication called post-transplant lymphoproliferative（淋巴组织增生的） disorder (PTLD) – five patients total in the BENEFIT trial, compared to one with cyclosporine. PTLD is associated with infection with the Epstein-Barr virus, which many humans have as a low-level chronic infection. The authors say PTLD might be reduced by avoiding use of belatacept in Epstein-Barr-naïve patients.