Outcome of Simultaneous Kidney Liver Transplantation (SLKT) according to the presence of post-transplant HLA alloantibodies
Valeria Descalzi1, Maria L. Reyes Toso1, Silvina E. Yantorno1, Marcela R. Fortunato2, Pablo M. Raffaele2, Ulises Toscanini3, Karim Padros3, Gabriel E. Gondolesi1.
1Liver Transplantation Unit , Favaloro Foundation University Hospital, Buenos Aires, Argentina; 2Kidney Transplantation Unit, Favaloro Foundation University Hospital, Buenos Aires, Argentina; 3PRICAI (Immunogenetic Center), Favaloro Foundation University Hospital, Buenos Aires, Argentina
Introduction: Based on the theory that liver allograft (L) from the same donor, protects the kidney allograft (K) by modulating host alloimmunity by donor specific antibodies (DSA) neutralization, a pre-transplant sensitized status does not currently represent an absolute contraindication for SLKT. However, publications showing deleterious consequences of post-transplant alloantibodies (PTA) on survival of L and K function are becoming increasingly frequent.
Aim: To assess the impact of PTA (preformed or de novo) on the outcome of combined SLKT.
Patients and Methods: Between 2010 to 2019; 36 SKLT in adult patients (pts) were performed at our center. 16 pts with both pre-transplant (PrTA) and PTA screening were included in the analysis. According to the existence or not of the PTA, pts were divided into 2 groups: PTA (+) and PTA (-). Primary endpoints were mortality, allograft loss and rejection rate. Demographics, immunological and transplant variables were compared in both groups. HLA antibodies screening was done by panel reactive antibodies (PRA) or HLA antibodies detection by luminex according to existent technology. Specificities were identified using a solid phase single antigen bead platform combined with luminex xMAP.
Statistical Analysis: Chi Square, T- test for univariate analysis and Kaplan Meier for actuarial survival, p ≤0,05 was considered statistically significant.
Results: All transplants were simultaneous: 12 (75%) with a 1st L and K, 3 (19%) 2nd or 3rd L + 1st K, and 1 (6%) 2nd K with a 1st L. Mean age was 53±14 yrs, 56% male, median follow up after SKLT was 1.7 (0.1-9.4) yrs. Main etiologies for ESLD were alcohol 25%, HCV 12.5% and ductopenic rejection 12.5%. Main etiologies for ESRD were indeterminate 37%, CNI associated 19%, and polycystic disease 12.5%. MELD at transplant was 26±5. PrTA were positive in 7 (44%) pts, (3 demonstrated DSA). PTA(+) group, was conformed by 7 (44%) pat: 4 developed de novo and 3 had preformed antibodies. Among the 9 pts (56%) in PTA(-) group: 5 (55%) negativized their previous positive status, and 4 never developed antibodies until the end of follow up. Pts, L and K survival in PTA (+) and (-) at 1, 3- and 5-years post-transplant was 83% / 89% (p=NS). Most frequent causes of mortality were infections 54% and cardiovascular 27%. Antibody mediated rejection (AMR) rate on L and K was 12% and 19% respectively, 1 pt in PTA (+) and 2 pts in PTA(-) (p=NS). No cellular rejection was reported.
Conclusions: 1) Although still not statistically significant, our results show that PTA have a negative impact on patient and graft survival. 2) AMR was similar in both groups; however, progressive idiopathic fibrosis of L was reported as a DSA related disease in 2 pts; that will lead to graft loss if undetected and untreated. 3) Follow-up protocols on DSA titers after SKLT have been seldomly reported; once technology becomes available, DSA screening should be routinely performed and considered standard of practice in the LT field.