Multiple high MFI Class I DSA can cause acute AMR of kidney allograft in simultaneous liver and kidney transplant recipients: outcome analysis from a single-center

Abstract

Aim Crossmatch (xM) positive (+ve) simultaneous liver and kidney transplant (SLKT) recipients remain at risk for antibody-mediated rejection (AMR) of the kidney allograft. To investigate the risk associated with donor-specific HLA antibodies (DSA), we studied 23 consecutive patients who received a SLKT at UCSF since 12/2013. Methods Donors and recipients were HLA-typed using Luminex rSSO. Recipient sera collected pre-tx, 1 wk and 3 mo post-tx were analyzed for HLA antibodies using Luminex single antigen beads. CPRA was determined using 2000 MFI cutoff. Immunosuppression was steroids, tacrolimus, and mycophenolate without induction. AMR was diagnosed by kidney biopsy. Results Among 23 patients (pts), 17 (74%) had CPRA>1%; 6 (26%) had CPRA>85%. Eight pts had pre-tx DSA: 6 with class I only; 1 had class II only, and 1 had both class I+II. Four pts had > 2 DSAs. Most DSAs (and CREG) were lost by 1 wk post-tx but non-DSAs persisted >3 mos (Figure). Two pts with 0% CPRA developed a de novo DSA at 3 mos: 1 had B44 (MFI 5589), other had DQA05 (MFI 2303). Two pts developed early kidney AMR. Pt 1 (CPRA100%) with 5 high MFI (>20K MFI) class I DSAs (A1, A24, B7, B37, Cw7) and +ve CDC & +ve Flow TB previous liver tx recipient) received SLKT from a well-matched (1C, 2DR, 2DQ, 1DP; no repeat mismatch) donor with +ve CDC and weakly +ve Flow T&B cell xMs. Allo-xM with 3rd party donors and auto-xM were CDC +ve but Flow -ve. All CDC xMs were -ve with heat-inactivated complement. xM with a 3rd party endothelial cell-line was weakly +ve. Renal allograft function recovered with AMR treatment. Conclusion Reduction of circulating HLA antibody titers after SLKT appears to be donor HLA (and CREG) specific. Kidney AMR occurred with multiple high MFI Class I DSAs or complement-fixing non-HLA IgG antibodies. Longitudinal analyses show the specificity, kinetics, and stability of HLA antibody absorption by liver allografts. Download : Download full-size image