Summary of FDA Antibody-Mediated Rejection Workshop

Abstract

The Food and Drug Administration (FDA) held an open public workshop in June 2010 to discuss the current state of science related to antibody-mediated rejection (AMR) in kidney transplantation. Desensitization, acute AMR and chronic AMR (CAMR) were considered in the context of clinical trial design. Participants discussed experiences with HLA antibody detection and quantitation and the utility of monitoring donorspecific antibodies (DSAs) to inform the management of patients with AMR. The role for animal models was discussed. Diagnostic and prognostic features of histology were presented, followed by discussion of sensitivity and specificity of various criteria. The published literature on treatment of acute AMR was summarized, which consisted of case series and limited data from controlled clinical trials. Considerations for future clinical trials were presented, including endpoints and statistical evaluations of outcome. Although many issues need further consideration, the meeting enabled an important exchange of ideas between experts in the field.

Molecular Microscope Strategy to Improve Risk Stratification in Early Antibody-Mediated Kidney Allograft Rejection

“…Our study is the first to examine the risk of graft loss in a large population of early ABMR patients with extensive follow-up and standardized management using an FDA-approved therapeutic strategy, 14 in which we used contemporary tools for precise allograft phenotyping together with a systematic gene expression assessment in the allograft to represent the full spectrum of ABMR. The present study used a model of early disease using a very high-risk cohort with early ABMR, which led us to focus on the disease progression related to ongoing humoral process without interference with superimposed diseases seen in late ABMR cases.…”

“…To achieve this goal, we used a unique model of early disease (early biopsy-proven ABMR) with intensive follow-up and standardized management with Food and Drug Administration (FDA)-recommended therapeutic strategies. 14 This model led us to focus on the disease progression related to the ongoing humoral process without the interference from superimposed diseases seen in late ABMR cases.…”

Randomized Controlled Trial of High-Dose Intradermal Versus Standard-Dose Intramuscular Influenza Vaccine in Organ Transplant Recipients

“…For purposes of the study, we defined a positive specimen (including de novo donor specific antibody (DSA)) as having a MFI > 1000 and a change in MFI > 20% from pre to postimmunization (12,13). Twenty percent was selected as there is significant assay variability from one batch to another (14,15).…”

Acute and chronic antibody-mediated rejection in pediatric kidney transplantation

“…The recent widespread application of SPA-based tests in clinical practice has confirmed the higher sensitivity of these diagnostic methods. Conflictingly, however, a growing number of studies in kidney transplantation patients have also shown that only a portion of Luminex-detectable HLA antibodies appear to cause antibody-mediated rejection [25][26][27]. This differentiation between clinically relevant and irrelevant DSAs is a major challenge, both before and after kidney [24,27,28].…”