Mid-term Outcome of Donor Specific Antibody Positive Deceased Donor Kidney Transplantation with Peri-Transplant Desensitization
Klara Osickova1, Petra Hruba2, Janka Slatinska1, Antonij Slavcev3, Jiri Fronek4, Eva Honsova5, Ondrej Viklicky1,2.
1Dept. of Nephrology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; 2Transplant Laboratory, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; 3Dept. of Immunogenetics, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; 4Dept. of Transplant Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic; 5Dept. of Clinical and Transplant Pathology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Donor specific HLA-antibodies (DSA) remain a large barrier to successful kidney transplantation and there is a limited knowledge about desensitization strategies in deceased donor programs.
Anti HLA antibodies specificity in all wait-listed patients has been tested by Luminex since 2013 to tailor peri- and post-transplant immunosuppression. 100 deceased donor kidney transplant recipients with pre-transplant DSA >1000 MFI was included in this prospective observational study. Desensitization protocol consisted of plasma exchange (PE) prior to transplant and rATG (Thymoglobulin) induction along with IVIG 0.1-0.5 g/kg given at first week in patients with MFI ranging 1000-5000 (DSA+, n=69). This protocol was accompanied by post-transplant PE/PP and rituximab in patients with MFI>5000 MFI (DSA++, n=31). All patients had negative actual CDC crossmatch prior to pre-transplant PE. The 3-years transplant outcomes of two DSA-pos cohorts were analyzed and compared with 952 DSA-neg controls treated with anti-CD25 or rATG induction. All patients received TAC/MMF/St therapy.
1-year death-censored graft survival was similar in DSA-pos and DSA-neg groups (DSA+ 94.9%, DSA++ 92.3% and DSA- 94.8%) while at 3 years DSA-pos patients had inferior censored graft survival (DSA+ 83.1%, DSA++ 77.7%, DSA- 94.0%, p=0.05). The acute antibody mediated rejection (ABMR) incidence was 19% in DSA+ group while 42% in DSA++ group respectively (p<0.05). Univariate analysis showed higher PRA (p=0.01), HLA mismatch (p=0.016), longer dialysis (p=0.016), longer cold ischemia (p=0.008), male recipient gender (p=0.012), re-transplantation (p<0.001), DSA class II (p=0.018) and DQ/DP DSA (p=0.002) in DSA-pos patients who developed ABMR compared those who did not. The binary logistic regression with forward method identified two main significant predictors of ABMR: re-transplantation (OR: 0.08; 95% CI: 0.17-0.36; p=0.001) and HLA mismatch (OR: 1.63; 95% CI: 1.1-2.4; p=0.016). The model had 90.5 % specificity and 38.5% sensitivity to predict ABMR among DSA-pos patients.
In conclusion, the peri-transplant desensitization represents a viable tool that enables successful kidney transplantation to patients with moderate or even with high level of sensitization in a country without the access to acceptable mismatch program.
