Antibody Reduces Rejection After Kidney Transplant

Jim Kling

May 10, 2010

May 10, 2010 (San Diego, CA) — An antibody that blocks terminal complement activity reduces acute humoral rejection in highly sensitized recipients of living donor kidneys, according to research presented here at the American Transplant Congress (ATC) 2010. The drug was used in conjunction with plasma exchange therapy.

Sensitized patients, having high levels of donor-specific alloantibody (DSA), comprise perhaps up to a third of renal transplant patients. They frequently experience acute humoral rejection (AHR). The researchers investigated whether treatment with the humanized anti-C5 antibody eculizumab could prevent AHR.

The team enrolled 16 highly sensitized recipients of living donor kidneys. Patients were treated posttransplant with eculizumab for 1 to 17 months. The researchers compared the incidence of AHR to a historic group of 51 sensitized patients who had completed a similar protocol without eculizumab treatment.

One of 16 patients treated with eculizumab (6.25%) experienced an AHR episode, compared with 20 of 51 control subjects (40%) (P < .05).

In the control group, AHR occurred in 20 of 22 (94%) patients who developed high DSA after transplantation (B flow crossmatch channel shift >340; molecules of equivalent soluble fluorochrome, 24,000).

Among those receiving eculizumab, 10 patients developed high DSA, but only 1 developed AHR (P < .05), although they all showed early complement activation (C4d+).

Treatment with eculizumab prevented splenectomy, reduced the number of plasma exchanges, and preserved renal function in patients with high posttransplant DSA. Four patients with high DSA but no AHR displayed signs of chronic injury. Two developed transplant glomerulopathy and 2 developed endothelial cell activation.

The researchers concluded that eculizumab decreases AHR in sensitized renal transplant patients, leading to reduced morbidity and graft dysfunction. "Persistently high DSA levels may require additional therapy to prevent the development of chronic damage," they write in the abstract.

"Early antibody mediation is a major barrier to a successful transplant and one of the major causes of morbidity," Mark Stegall, MD, professor of surgery at the Mayo Clinic in Rochester, Minnesota, told Medscape Transplantation, noting that the drug represents an addition to conventional plasma exchange therapy. "I think we showed that the drug decreases the incidence of early antibody-mediated rejection, compared with the historical control group, and decreased morbidity in the first month. The drug makes the posttransplant management of these patients so much easier than it was before," Dr. Stegall added.

"It's encouraging to have a mechanism that might allow us to handle patients who develop antibodies after transplant," Maryl Johnson, MD, medical director of the Heart Failure Transplant Program at the University of Wisconsin at Madison, who comoderated the session, told Medscape Transplantation.

Dr. Johnson also noted that there are no good treatments for such patients. Still, the study is preliminary. "We need more studies to see if there will be a benefit long-term clinically," Dr. Johnson said.

The study received support from Millennium Pharmaceuticals and Alexion Pharmaceuticals. Dr. Johnson has disclosed no relevant financial relationships.

American Transplant Congress (ATC) 2010: Abstract 1. Presented May 2, 2010.

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