Association between post‐transplant donor‐specific antibodies and recipient outcomes in simultaneous liver–kidney transplant recipients: single‐center, cohort study

Abstract

There is a dearth of published data regarding the presence of post-transplant donor-specific antibodies (DSA), especially C1q-binding DSA (C1q+DSA), and patient and kidney allograft outcomes in simultaneous liver-kidney transplant (SLKT) recipients. We conducted a retrospective cohort study consisted of 85 consecutive SLKT patients between 2009 and 2018 in our center. Associations between presence of post-transplant DSA, including persistent and/or newly developed DSA and C1q+DSA, and all-cause mortality and the composite outcome of mortality, allograft kidney loss, and antibody-mediated rejection were examined using unadjusted and age and sex-adjusted Cox proportional hazards and time-dependent regression models. The mean age at SLKT was 56 years and 60% of the patients were male. Twelve patients (14%) had post-transplant DSA and seven patients (8%) had C1q+DSA. The presence of post-transplant DSA was significantly associated with increased risk of mortality (unadjusted model: Hazard Ratio (HR) = 2.72, 95% confidence interval (CI): 1.06-6.98 and adjusted model: HR = 3.20, 95% CI: 1.11-9.22) and the composite outcome (unadjusted model: HR = 3.18, 95% CI: 1.31-7.68 and adjusted model: HR = 3.93, 95% CI: 1.39-11.10). There was also higher risk for outcomes in recipients with C1q+DSA compared the ones without C1q+DSA. Post-transplant DSA is significantly associated with worse patient and kidney allograft outcomes in SLKT. Further prospective and large cohort studies are warranted to better assess these associations.

Kidney Graft Outcomes in High Immunological Risk Simultaneous Liver‐Kidney Transplants

“…(3) Our recent study (n = 85, 14% with posttransplant DSAs) showed that the presence of posttransplant DSAs was significantly associated with an increased risk of mortality (hazard ratio [HR], 5.15; 95% confidence interval [CI], 1.92-13.77) and composite outcomes that consisted of mortality, kidney allograft loss, and antibody-mediated rejection (HR, 5.95; 95% CI, 2.30-15.39). (4) Supporting our observation, the article by Piñeiro et al also indicated a higher kidney allograft rejection rate in the high sensitization group, (1) which might be a consequence of persistent posttransplant DSAs. This was supported by the findings of this article, a previous article by O'Leary et al, and our work ( Fig.…”

“…In particular, class 2 DSAs were more likely found in recipients with longer hospital stay and were associated with worse kidney graft outcomes. (4,5) Because liver transplantation is a life-saving procedure, we support the current practice to perform SLKT regardless of the pretransplant immunological risk. However, posttransplant DSAs should be handled as a potentially modifiable risk factor of kidney allograft outcome after SLKT.…”

“…However, posttransplant DSAs should be handled as a potentially modifiable risk factor of kidney allograft outcome after SLKT. (4) We strongly recommend routine measurement of DSAs after SLKT especially in the patients with class 2 DSAs before SLKT and unexplained kidney dysfunction after SLKT.…”

“…1), which showed that class 2 DSAs would not be sufficiently absorbed by the liver allograft in contrast with class 1 DSAs. (2)(3)(4) One of seven SLKT recipients had posttransplant DSAs. In particular, class 2 DSAs were more likely found in recipients with longer hospital stay and were associated with worse kidney graft outcomes.…”

Reply

“…(1,2) However, the persistence of class 2 DSA after SLKT or the development of de novo DSA has been associated with worse outcomes. (3)(4)(5) It has been proposed that class 2 DSAs may not be absorbed by the liver, but this is not the only immunomodulatory mechanism driven by the liver. (6,7) In our study, 4 patients were determined to have posttransplant class 2 DSAs out of 10 patients who had class 2 DSAs before transplant.…”