Predictive Potential of Flow Cytometry Crossmatching in Deceased Donor Kidney Transplant Recipients Subjected to Peritransplant Desensitization

Klara Osickova; Petra Hruba; Katerina Kabrtova; Jiri Klema; Jana Maluskova; Antonij Slavcev; Janka Slatinska; Tomas Marada; Georg A Böhmig; Ondrej Viklicky

doi:10.3389/fmed.2021.780636

Predictive Potential of Flow Cytometry Crossmatching in Deceased Donor Kidney Transplant Recipients Subjected to Peritransplant Desensitization

Front Med (Lausanne). 2021 Dec 14:8:780636. doi: 10.3389/fmed.2021.780636. eCollection 2021.

Authors

Affiliations

¹ Department of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czechia.
² Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czechia.
³ Department of Immunogenetics, Institute for Clinical and Experimental Medicine, Prague, Czechia.
⁴ Department of Computer Science, Faculty of Electrical Engineering, Czech Technical University, Prague, Czechia.
⁵ Department of Pathology, Institute for Clinical and Experimental Medicine, Prague, Czechia.
⁶ Aesculab Pathology, Prague, Czechia.
⁷ Department of Transplant Surgery, Institute for Clinical and Experimental Medicine, Prague, Czechia.
⁸ Division of Nephrology and Dialysis, Department of Medicine III, Medical University Vienna, Vienna, Austria.

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.

Keywords: HLA incompatibility; donor specific antibodies; flow cytometry; immunosuppression; kidney; rejection; transplantation-kidney.