Optimizing Transplantation of Sensitized Kidney Recipients through Prioritization of Unacceptable Antigen Assignment.

Abstract

Background: The calculated PRA (CPRA) was implemented as part of the OPTN/UNOS kidney allocation system on October 1, 2009, based on the frequency of antigens determined to be unacceptable (UAs) in the donor pool for a given patient. It is incumbent on each center to establish criteria for UAs assignment based on their ability to transplant (tx) sensitized recipients (recips). The aim of our study was to establish an algorithm for assignment of UAs such that a complement dependent cytotoxicity crossmatch (CDC-XM) would be negative and a concomitant flow cytometric crossmatch (FXM) would be weakly positive to allow for successful tx of sensitized kidney recips. Methods: Four antibody (Ab) methods were used to determine specificity, function, and strength of the Ab: C1q binding, CDC panel, Luminex single antigen (LSA), and LSA with a 1:8 dilution. UAs were assigned in the following order: 1) C1q/CDC+; 2) LSA 1:8 >7,500 MFI; and LSA >10,000 MFI. Results: Between January 4, 2010 and July 6, 2013, 345 recips received deceased donor (DD) tx, including 194 with no detectable antibodies to HLA (HLA-Abs) and 151 with HLA-Abs. Of the 151, 20 recips (13%) received zero mismatch grafts and were excluded from further analysis. For the remaining 131 recips, only DD with no C1q binding UAs and negative CDC XMs were considered for tx. The 3 categories of FXM were: 1) T neg/B neg = 66 recips (50.4%); 2) T neg/B pos = 32 recips (24.4%); and 3) T pos/B pos = 33 recips (25.2%) (table). Antibody mediated rejection (ABMR) rates for each category were: 1) 7 (10.6%); 2) 6 (18.8%); 3) 8 (24.2%). The overall ABMR rate for HLA-Abs+ recips = 21.5%. Conclusions: Careful assignment of UAs has allowed for 38% of HLA-Ab+ recips to be tx'ed successfully with HLA disparate DD grafts and an overall rejection rate of 21.5%. The C1q binding assay proved to be valuable to identify those antigens that must be avoided to optimize a negative CDC-XM and weak FXM. Strategies for assigning UAs are imperative to assign a CPRA status reflective of the sensitization level for recips and thereby optimize transplantation of HLA-Ab+ recips.Table: No Caption available.DISCLOSURES:Jordan, S.: Grant/Research Support, CSL-BEHRING, GENENTECH-ROCHE.