Abstract
Recipient sensitization is a major risk factor of antibody-mediated rejection (ABMR) and inferior graft survival. The predictive effect of solid-phase human leukocyte antigen antibody testing and flow cytometry crossmatch (FCXM) in the era of peritransplant desensitization remains poorly understood. This observational retrospective single-center study with 108 donor-specific antibody (DSA)-positive deceased donor kidney allograft recipients who had undergone peritransplant desensitization aimed to analyze variables affecting graft outcome. ABMR rates were highest among patients with positive pretransplant FCXM vs. FCXM-negative (76 vs. 18.7%, p < 0.001) and with donor-specific antibody mean fluorescence intensity (DSA MFI) > 5,000 vs. <5,000 (54.5 vs. 28%, p = 0.01) despite desensitization. In univariable Cox regression, FCXM positivity, retransplantation, recipient gender, immunodominant DSA MFI, DSA number, and peak panel reactive antibodies were found to be associated with ABMR occurrence. In multivariable Cox regression adjusted for desensitization treatment (AUC = 0.810), only FCXM positivity (HR = 4.6, p = 0.001) and DSA number (HR = 1.47, p = 0.039) remained significant. In conclusion, our data suggest that pretransplant FCXM and DSA number, but not DSA MFI, are independent predictors of ABMR in patients who received peritransplant desensitization.
Highlights
Preformed antibodies directed against donor human leukocyte antigen (HLA) antigens represent a major obstacle in kidney transplantation, limiting both access to transplantation and kidney allograft survival [1, 2]
Kidney transplantation across the HLA barrier is associated with an inferior allograft outcome
It is widely acknowledged that the presence of preformed donor-specific antibodies (DSA) before transplantation increases the probability of antibody-mediated rejection (ABMR) occurrence [12–15]
Summary
Preformed antibodies directed against donor human leukocyte antigen (HLA) antigens represent a major obstacle in kidney transplantation, limiting both access to transplantation and kidney allograft survival [1, 2]. It is widely accepted that kidney transplantation across donor-specific antibodies (DSA) identified either by solid-phase assays or flow cytometry crossmatch (FCXM) is associated with a higher risk of antibody-mediated rejection (ABMR) and inferior allograft outcomes, even in absence of positive complement-dependent cytotoxicity crossmatch (complement-dependent cytotoxicity crossmatch [CDC XM]) [3–7]. Kidney transplantation with a low level of DSA with or without a low positive B-cell FCXM was found to be associated with satisfactory outcomes in highly sensitized mostly living donor kidney transplant recipients who received depleting antibody induction and frequently desensitization [12]. In HLA incompatible deceased donor kidney transplantation with peritransplant desensitization, outcome predictors are poorly understood In this retrospective single-center observational cohort study, we assessed several variables to predict antibody-mediated rejection in those DSA positive deceased donor kidney transplant recipients who had undergone peritransplant desensitization
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