Faculty Bibliography

RATIONALE AND OBJECTIVE/OBJECTIVE:Compared to recipients of ABO-compatible (ABOc) living donor kidney transplants (LDKT), recipients of ABO-incompatible (ABOi) LDKT have a higher risk of graft loss, particularly in the first few weeks after transplantation. However, the decision to proceed with ABOi LDKT should be based on a comparison of the alternative: waiting for future ABOc LDKT (e.g, through kidney paired exchange) or for a deceased donor kidney transplant (DDKT). We sought to evaluate the patient survival difference between ABOi LDKT and waiting for an ABOc LDKT or an ABOc DDKT. STUDY DESIGN/METHODS:Retrospective cohort study of adults in the Scientific Registry of Transplant Recipients (SRTR) SETTING AND PARTICIPANTS: 808 ABOi LDKT recipients and 2423 matched controls from among 245,158 adult, first-time kidney-only waitlist registrants who did not receive an ABOi LDKT and who remained on the waitlist or received either an ABOc LDKT or an ABOc DDKT, 2002-2017 EXPOSURE: Receipt of ABOi LDKT OUTCOME: Death ANALYTICAL APPROACH: We compared mortality among ABOi LDKT recipients versus a weighted matched comparison population using Cox proportional hazards regression as well as Cox models that accommodated for changing hazards ratios over time. RESULTS:Compared to matched controls, ABOi LDKT was associated with lower survival risk in the first 30 days post-transplant (99.0% vs 99.6%, respectively), but higher survival risk beyond 180 days post-transplant. Patients who received ABOi LDKT had higher survival at 5 and 10 years (90.0% and 75.4% respectively) than similar patients who remained on the waitlist or received ABOc LDKT or ABOc DDKT (81.9% and 68.4% respectively). LIMITATIONS/CONCLUSIONS:No measurement of ABO antibody titers in recipients; eligibility of participants for kidney paired donation is unknown. CONCLUSIONS:Transplant candidates who receive an ABOi LDKT and survive more than 180 days post-transplant experience a long-term survival benefit compared to remaining on the waitlist to potentially receive an ABO compatible kidney transplant.

Purpose: In heart transplantation (HT), antibodies directed against Angiotensin II type 1 receptor (AT1RAb) have been associated with antibody-mediated rejection (AMR), acute cellular rejection (ACR), and microvasculopathy. The effect of AT1RAb detected pre-HT on immediate post-HT allograft injury remains poorly defined. In this study, we leverage a validated and sensitive blood based biomarker for allograft injury, donor-derived cell-free DNA (ddcfDNA), to examine the association of pre-HT AT1RAb to post-HT allograft injury.
Method(s): AT1RAb testing was performed on pretransplant plasma from HT recipients in the Genomic Research Alliance for Transplantation (GRAfT) multicenter, prospective cohort study, using a quantitative ELISA (One Lambda, ThermoFisher). After HT, serial plasma samples were collected and used to quantitate %ddcfDNA by shotgun sequencing. AT1RAb concentration (units/ml) was used to categorize patients as AT1RAb<30 (n=32) or AT1RA>30 (n=17). A mixed linear model was used to examine post-HT %ddcfDNA trajectories across AT1RAb groups. Histopathology slides were read by a consensus of pathologists to define AMR using ISHLT criteria.
Result(s): Age, gender and clinical features were similar between AT1RAb<30 and AT1RA>30 groups. AT1RAb>30 had a greater proportion of White recipients compared to AT1RAb<30 (59% versus 38%; p = 0.003). While %ddcfDNA on posttransplant Day 1 were similar between AT1RAb<30 vs AT1RAb>30 (p=0.6), in the first year post-HT, ddcfDNA declined by 87% (95% CI 79%-92%) among patients with AT1RAb<30 vs 67% (CI=34%-84%) among patients with AT1RAb>30 (p = 0.04) (Figure). AMR in the first year post-HT was more common among AT1RAb>30 than AT1RAb<30 patients (18% vs 3%, p=0.07); CMR was comparable in each group (41% vs 24%, p=0.2).
Conclusion(s): Preliminary analysis of this heart transplant cohort suggest that high pre-HT AT1RAb is associated with increased early post-HT allograft injury.
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