Introduction: Pre-transplant anti-human leukocyte antigen (HLA) donor specific antibodies (DSA) have been known to be associated with outcomes after kidney transplantation. In particular, several studies have demonstrated that DSA affects early antibody-mediated rejection (ABMR). The aim of this study was to investigate factors affecting early pathologic outcome in recipients with pre-transplant DSA.
Materials and Methods: Between January 2008 and September 2019, data were collected retrospectively at a single center. Histologic outcomes reviewed post-transplant protocol (0 day, 10 days, and 1 year) and indication biopsy. Associations between ABMR or any rejection and factors such as induction agents, panel reactive antibody (PRA), DSA median fluorescence index (MFI), ABO incompatible (ABOi), and flow cytometric crossmatch (FCXM) were analyzed.
Results and Discussion: A total of 80 pre-transplant DSA positive patients were included. The ABO incompatible was 14 (17.5%), and FCXM positive was 21 (26.3%). Of the recipients with FCXM positive, 14 were resolved negative after desensitization and the other 7 unresolved were B cell type. Pretransplant desensitization was performed in 57 (71.3%) cases [Rituximab, 57; plasmapheresis and intravenous immunoglobulin (IVIG), 52; Bortezomib, 5]. Immediate pretransplant DSA MFI median values were 782. Overall, the patients had the features of weak pretransplant DSA. Thirty eight (47.5%) used Basiliximab as induction agent, 41 (51.3%) used anti-thymocyte globulin (ATG), and one did not use any agent. In multivariable analysis, Basiliximab had a significantly higher incidence rate of rejection compared to ATG at 1 month, 3 months, and 1 year (p <0.001, p <0.001, and p = 0.012). Anti-HLA class I DSA was 31 (38%) patients, class II DSA was 34 (42.5%) patients, and class I & II DSA was 15 (18.8%), and there were no significant differences in ABMR or rejection among them. Immediate pretransplant DSA MFI values ​​were not significantly different between the no rejection group and the rejection group at 1 month [median (IQR, interquartile range), 691 (0-1084) vs 984 (466-1552), p = 0.325], 3 months [691 (0-1032) vs 984 (373-1564), p = 0.394], and 1 year [711 (0-967) vs 809 (51-1406), p = 0.713] after kidney transplantation. In addition, there were no significant differences in the pathologic outcome with 1 year rejection or ABMR between groups with immediate pre-transplant DSA MFI values < 1000 and ≥ 1000 (p = 0.111, p = 0.882).
Conclusion: The use of ATG over basiliximab is strongly recommended in kidney transplant recipients with weak pretransplant DSA due to higher biopsy-proven rejection rates within 1 year of transplant for basiliximab induction. However, pretransplant DSA or PRA MFI did not predict ABMR or any rejection whether before or after desensitization. Also, FXCM and ABOi were not associated with early histologic outcomes.