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Background Calcineurin inhibitor (CNI) based immunosuppression in liver transplantation (LTx) is associated with acute and chronic deterioration of kidney function. Delaying CNI initiation by using induction rabbit anti-thymocyte globulin (rATG) may provide kidneys with adequate time to recover from a perioperative insult reducing the risk of early post-LTx renal deterioration. Methods This was an open-label, multicenter, randomized controlled clinical trial comparing use of induction rATG with delayed CNI initiation (day-10) against upfront CNI commencement (SOC; standard of care) in those patients deemed at standard risk of postoperative renal dysfunction following LTx. The primary end point was change in (delta) creatinine from baseline to month-12. Results Fifty-five patients were enrolled in each study arm. Mean Tacrolimus levels remained comparable in both groups from day-10 throughout the study period. A significant difference in delta creatinine was observed between rATG and SOC groups at 9-months (p=0.03) but not at month-12 (p=0.05). eGFR levels remained comparable between cohorts at all time points. Rates of biopsy-proven acute rejection at 1-year were similar between groups (16.3 vs 12.7%, p= 0.58). rATG showed no significant adverse effects. Survival at 12-months was comparable between groups (p= 0.48). Conclusions Although the use of induction rATG and concurrent CNI deferral in this study did not demonstrate a significant difference in delta creatinine at 1 year, these results indicate a potential role for rATG in preserving early kidney function, especially when considered with CNI deferral beyond 10 days and/or lower target Tacrolimus levels, with acceptable safety and treatment efficacy.

Background Although antibody-mediated rejection (AMR) is described in other solid organ transplant populations, the literature describing the management following lung transplantation is limited. Objective The purpose of this study is to evaluate the management strategies of AMR in lung transplant recipients. Methods This single-center, retrospective study described the management of AMR in adult lung transplant recipients who received treatment with rabbit antithymocyte globulin, bortezomib, rituximab, intravenous immune globulin (IVIG), and/or plasmapheresis between September 2015 and June 2019. Results A total of 270 medication orders for 55 patient admissions were included in the primary outcome analysis. The most commonly used regimen consisted of IVIG, plasmapheresis, and rituximab (49.1%; n = 27), followed by IVIG and plasmapheresis alone (27.3%, n = 15). A total of 51 patients (93%) received plasmapheresis as part of their AMR treatment, with a median of 4 [3, 5] sessions per encounter; 86% of patients with positive donor-specific antibodies (DSAs) had a reduction in DSAs following AMR treatment. Overall, 23.5% of patients had noted allograft failure or need for retransplantation. A total of 10 patients died during the AMR treatment hospital admission, and an additional 11 patients died within 1 year of the initial encounter. Conclusion and Relevance This represents the largest report describing management strategies of AMR in lung transplant recipients. Although practice varied, the most commonly used regimen consisted of plasmapheresis, IVIG, and rituximab.

Objective: To review the use of rabbit antithymocyte globulin (rATG) induction therapy in liver transplant recipients. Data Sources: A MEDLINE literature search (inception to March 2016) was conducted using the search terms rabbit antithymocyte globulin, liver transplantation, and induction. References from extracted sources were further searched for any relevant, missed data sources. Study Selection and Data Extraction: All English-language randomized and observational studies were included. Data Synthesis: A total of 9 studies were included in this review evaluating rATG’s use for induction therapy. All studies were single-center analyses. rATG induction is utilized to delay calcineurin inhibitor initiation and to minimize or avoid steroids. Patients receiving rATG induction tended to have improved renal function compared with patients not receiving induction. Overall, rejection rates tended to be lower in recipients administered rATG. Regimens varied in each study, with most recipients receiving 2 to 3 doses of induction therapy. Conclusions: rATG induction therapy may lead to improved renal function and lower rejection rates following liver transplant. The use of this medication can help avoid unwanted adverse effects from other immunosuppression agents. Because of the potential benefits with this induction agent, rATG may have a larger role in induction therapy for liver transplant recipients.

Aim Mortality of Acute Graft vs. Host Diseases (aGvHD) after Liver Transplantation (LT) can be as high as 70–100%, due to delays in diagnosis and severity of complications. Based on a large LT cohort with long term follow up, we investigated the role of donor chimerism (D%) in supporting expeditious aGvHD diagnosis and monitoring disease control. Methods 145 of 1478 recipients with LT during 9/2007-12/2017 were clinically suspected to have aGvHD and tested for D% with peripheral blood (PB), CD3 + (T), CD8 + T, NK, and B lymphocytes by short tandem repeat (sensitivity 5%). D% at initial testing and peak stage, POD of aGvHD resolution, and aGvHD related mortality were retrospectively analyzed. Clinical suspicions with CD8 + T D% >25% were initially treated with methylprednisolone and/or reduced immunosuppression. Thymoglobulin was added to cases with no improvement after initial therapy. Results The D% in PB was uninformative. The highest D% was seen in CD8 + T cells followed by T cells and NK cells. Of 145 recipients with D% test, 27 had D% > 5, these patients were then graded into clinical severity as C0-3. Nine patients in C0 had no clinical evidence of aGvHD, whereas 18 patients were graded as C1-3. C2 and C3 (n = 9) had average CD8 + T D% ⩾ 75±23% at initial testing and ⩾ 86±24% at peak D% stages, which were significantly higher than that of C1 (n = 9) with p Conclusions The D% of CD8 + T cell is a sensitive and correlative indicator for timely diagnosis and effective monitoring of aGvHD after LT. High D% of CD8 + T from initial testing and peak phase was associated with aGvHD related mortality or prolonged resolution of this disease. Early detection of D% of CD8 + T before the donor immune system fully engrafted is critical for recovering from the damage of aGvHD following LT.

Key Points 1. Our increasing understanding of signaling pathways and cellular interactions in transplant immunobiology and the availability of novel immunosuppressive agents have facilitated targeted strategies. 2. The driving forces behind the development of new immunosuppressive regimens are the long-term complications of current immunosuppressive regimens (particularly renal dysfunction and metabolic disturbances). 3. By regulatory mandate, the requirement for the primary endpoint to be a composite of death, graft loss, and rejection remains intact; however, current and future clinical trials could incorporate key secondary endpoints that address renal and metabolic derangements. Liver Transpl, 2011. © 2011 AASLD.