Combining sensitive crossmatch assays with donor/recipient human leukocyte antigen eplet matching predicts living-donor kidney transplant outcome

Abstract

Introduction: Despite the different assays available for immune-risk stratification before living-donor kidney transplantation (LDKT), the precise type and number of tests to perform remain uncertain. Methods: In a cohort of 330 consecutive LDKT patients, all of which were complement-dependent cyto- toxicity (CDC) crossmatch negative, we retrospectively analyzed the impact on main clinical outcomes of most sensitive immunoassays (complement-dependent cytotoxicity panel-reactive antibody [CDC-PRA], flow cytometry crossmatch [FC-XM], donor-specific antibodies [DSAs], and their complement-binding capacity DSA-C3d]), together with donor/recipient HLA eplet matching. Mean follow-up was 67 months (range 24 190 months). Results: Of 330 patients, 35 (11%) showed a CDC-PRA >20%; 17 (5%) FC-XMþ; 30 (9%) DSAþ, 18(5%) DSA- C3dþ, with low overlapping results (10 patients positive in all donor-specific tests). Unlike HLA allele compatibility, the mean number of HLA class II eplet mismatches was higher in LDKT patients with positive baseline test results. DSA-C3dþ showed higher mean fluorescence intensity (MFI) DSA, with a cut-off MFI of 6192 accurately predicting complement fixation (area under the curve 1⁄4 0.85, P 1⁄4 0.008). Although all assays were associated with acute rejection (AR), only DSA-C3dþ (odds ratio [OR] 1⁄4 6.64, P 1⁄4 0.038) or high MFI-DSA (OR 1⁄4 7.54, P 1⁄4 0.038) independently predicted AR. Likewise, poorly HLA class II eplet matched patients were at higher risk for AR, particularly patients with negative baseline test results (OR 1⁄4 1.14, P 1⁄4 0.019). Finally, previous AR and FC-XMþ/DSAþ, regardless of C3d positivity, indepen- dently predicted graft loss. Conclusion: Combining FC-XM and solid-phase assays with the evaluation of donor/recipient HLA eplet mismatches, are most accurate tools for immune-risk stratification prior LDKT.