Anti-HLA donor-specific antibody pretransplant assessment impact on long-term outcomes after kidney transplantation
Cristina Q C Glehn1, Jorge L Z Ramos2, Magnus Engel2, Renata Glehn-Ponsirenas1, Carlos A M Aita3, Vanessa Soutomaior4.
1Immunogenetics Laboratory, Cajuru University Hospital, Curitiba, Brazil; 2Pato Branco Policlinic, Pato Branco Policlinic , Pato Branco, Brazil; 3Division of the Pathology, DB Laboratory, Curitiba, Brazil; 4Healthy Science Medical School, Pontifical Catholic University ParanĂ¡, Curitiba, Brazil
Background/Purpose: Risk assessment of preformed anti-HLA antibodies is common practice in kidney transplantation. The implementation of Single Antigen Bead assays (SABs) allowed for ability to identify donor-specific antibodies (DSA) leading to better inference of risk compared with the previous frequency of panel reactivity antibodies (%PRA) utilized in clinical practice. Here we evaluated the impact in long-term outcomes of the implementation of DSA information pre-transplantation in the clinical management of risk in comparison with long-term outcomes of patients managed based on %PRA information.
Methodology: We included 315 kidney transplant recipients, 122 in Group 1 (G1) were transplanted before the introduction of SAB test and the risk assessment was based on %PRA information, and 193 transplants in Group 2 (G2) transplanted with risk assessment based on DSA or Non-DSA information. Patients in Group 1 were considered high risk if PRA above 76%, and patients in Group 2 were considered high risk only in the presence of DSA above 500 MFI.
Results: In G1, the higher the %PRA, the higher the rate of graft loss in 8 years (61.11%, 51.11% and 29.27%, respectively from the highest sensitization range to the lowest, p=0.012) for Group 2, the degree of sensitization did not influence in graft survival (23.33%, 18.03% and 18.63%, p=0.79). Both groups presented similar characteristics and no changes in the patients' pre-transplant clinical management and immunosuppressive medications. The main difference between G2 and G1 was the definition of risk for the post-transplant clinical management strategy and immunosuppression adjustments, which was based on information on the percentage of PRA for G1 and the presence or absence of DSA for G2. This resulted in an 8-year overall survival for G2 of 80.8% (G1=53.3%, p = 0.0009). Furthermore, G2 showed better overall graft function over 8 years of follow-up, mean serum creatinine ≤ 130 micromol/l compared to G1 (72% x 59%).
Conclusion: This study shows the real impact in long-term outcomes in this population with the use of DSA pre-transplant as a tool for risk stratification and establishment of post-transplant clinical management. The presence or absence of DSA has a greater influence on graft survival and should therefore be considered when choosing immunosuppressive therapies. Patients with DSA had a closer antibody monitoring post-transplantation and appropriated induction and immunosuppression therapy, while highly sensitized patients with no-DSA benefited from the use of lower levels of immunosuppression improving overall survival.
[1] Kidney transplant
[2] HLA DSA