ATC2015: Blocking B7 in Kidney Transplantation, Is It Effective in Preventing FSGS?

The American Transplant Congress (ATC) is the joint annual meeting of the American Society of Transplant Surgeons (ASTS) and the American Society of Transplantation (AST) and is taking place in Philadelphia, Pennsylvania, from May 2-6, 2015. The AJKD Blog will be providing some highlights from the conference.

A 2013 case series published in the New England Journal of Medicine suggested a novel target and treatment for FSGS. Abatacept, which blocks B7-1, was found to induce remission of FSGS. This is of interest in kidney transplantation because recurrent FSGS has been found to occur in up to 30% of transplant recipients and belatacept, an FDA-approved medication for maintenance immunosuppression in kidney transplantation, actually blocks B7-1.

Belatacept works by blocking two molecules, B7-1 and B7-2, which are important in the co-stimulatory pathway for T cell activation. It binds to B7-1 with higher affinity than abatacept. Patients with FSGS were excluded from the seminal studies that got belatacept FDA approved for kidney transplantation. An abstract presented yesterday by Kitchens et al from Emory attempted to answer whether belatacept prevents recurrent FSGS in transplant recipients. They compared the incidence of recurrent FSGS in 50 patients treated with belatacept-based immunosuppression where 17 historical controls received tacrolimus-based immunosuppression. Unfortunately, the incidence of recurrent FSGS was almost identical in both groups (12% in the belatacept group vs. 11.8% in the historical controls). There were no differences in the incidence of acute rejection and differences in GFR were not statistically significant between the two groups. They did not look at the degree of proteinuria and they did not stain for B7 in the biopsies.

Does this mean there is no role for blocking B7 in prevention and treatment of FSGS in kidney transplantation? Not necessarily as there are differences between belatacept and abatacept that could potentially account for the lack of efficacy. However, belatacept per se, although safe and effective, does not appear to prevent recurrent FSGS in kidney transplant recipients.

Post written by Dr. Vinay Nair, AJKD Blog Advisory Board member.

Check out more AJKD blog coverage of the 2015 American Transplant Congress.

 

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