Inducing transient mixed chimerism for allograft survival without maintenance immunosuppression with combined kidney and bone marrow transplantation: Protocol Optimization Background. Tolerance induction is an important goal in the field of organ transplantation. We have sequentially modified our conditioning regimen for induction of donor-specific tolerance in recipients of major histocompatibility complex (MHC)-mismatched combined kidney and bone marrow transplantation (CKBMT). Methods. From December 2011 to May 2017, eight MHC-mismatched patients received CKBMT. The initial conditioning regimen (Protocol 1) consisted of cyclophosphamide (CP), rituximab, antithymocyte globulin (rATG), and thymic irradiation. Tacrolimus and steroids were used for the maintenance of immunosuppression (IS). Results. This regimen was complicated by transient acute kidney injury which has been the major clinical feature of engraftment syndrome and side effects of CP, although one of two subjects successfully discontinued his IS for 14 months. The conditioning regimen was modified by reducing the CP dose and adding fludarabine (Protocol 2). The final modification was reducing the fludarabine and rATG doses (Protocol 3). Mixed chimerism, detected by the short-tandem repeat method, was achieved transiently in all subjects for 3-20 weeks. Among the three subjects treated with Protocol 2, IS was successfully discontinued for >35 months in one subject, but the other two subjects suffered from severe BK virus associated nephritis (BKVAN). All three subjects treated with Protocol 3 tolerated the protocol well and have successfully discontinued IS for >4-41 months. Interestingly, de novo DSA was not detected in any subject during all the follow-up periods. Conclusions. Our clinical trial has shown that long-term renal allograft survival without maintenance IS can be achieved by induction of mixed chimerism following CKBMT. Disclosure of potential Conflict of interest: The authors indicated no potential conflicts of interest. Funding: This work was supported by a grant from the Korean Health Technology R&D project, Ministry of Health and Welfare, Republic of Korea (HI13C1263). This work also supported by Samsung Medical Center grant (GFO0170041). Correspondence: Jae Berm Park, MD, PhD Professor Department of Surgery, Samsung Medical Center, Sunkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul, 06351, Korea Tel: +82-2-3410-3647; Fax: +82-2-3410-0400; E-mail: jbparkmd@gmail.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Clinicopathologic Assessment of Monoclonal Immunoglobulin-Associated Renal Disease in the Kidney Allograft. A Retrospective Study and Review of the Literature. Background: Monoclonal immunoglobulin (MIg) associated renal disease (MIgARD) comprises a group of disorders caused by direct deposition of paraproteins in the kidney. Allograft MIgARD is infrequently encountered and poorly characterized. Methods: First, we assessed our allograft biopsies diagnosed with MIgARD between 2007-2018. The cohort included 26 patients: proliferative glomerulonephritis with MIg deposits (PGNMID) (n=13), AL amyloidosis (n=5), light chain deposition disease (n=5), light chain proximal tubulopathy (n=2), and light chain cast nephropathy (n=1). Second, we conducted a literature review to evaluate the rare non-PGNMID entities. We identified 20 studies describing 29 patients that were added to our cohort (total n=42). Results: Part-1: Patients’ median age was 55, 31% were women, and 19% were blacks. Twelve patients (46%) lost their grafts at a median of 8 months after diagnosis. Compared to non-PGNMID, PGNMID patients had lower frequency of detectable paraproteins (31% vs. 92%, P=0.004) and hematologic neoplasms (23% vs. 77%, P=0.02). Within PGNMID group, 6 patients changed their apparent immunofluorescence phenotype between monotypic and polytypic while all 3 patients with hematologic neoplasms had substructure on electron microscopy. Part-2: Whereas light chain cast nephropathy occurred the earliest and had the worst graft survival, AL amyloidosis occurred the latest and had the best graft survival. Conclusions: MIgARD in the kidney allograft is associated with poor prognosis. While posttransplant PGNMID can change its apparent clonality by immunofluorescence supporting oligoclonal immune responses, the presence of deposit substructure is an important indicator of underlying hematologic neoplasm. Non-PGNMID are often associated with hematologic neoplasms and varied prognosis. ACKNOWLEDGMENTS:This research was presented in part at the American Transplant Congress for which JK received the American Society of Transplantation Kidney Pancreas Community of Practice (KPCOP) Travel Grant. Financial disclosure IB is supported by AST Research Network/Astellas Faculty Development Research Grant. Disclaimer: The authors declare no conflicts of interest. Correspondence: Jeanne Kamal, Columbia University Medical Center, PH4-124, 622 West 168th Street, New York, NY, 10032, kamaljeanne@gmail.com, 1 (347)622-0729 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

A strategy for suppressing macrophage-mediated rejection in xenotransplantation Although xenografts are one of most attractive strategies for overcoming the shortage of organ donors, cellular rejection by macrophages is a substantial impediment to this procedure. It is well known that macrophages mediate robust immune responses in xenografts. Macrophages also express various inhibitory receptors that regulate their immunological function. Recent studies have shown that the overexpression of inhibitory ligands on porcine target cells results in the phosphorylation of tyrosine residues on intracellular immune receptor tyrosine-based inhibitory motifs (ITIMs) on macrophages, leading to the suppression of xenogenic rejection by macrophages. It has also been reported that myeloid derived suppressor cells (MDSC), a heterogeneous population of immature myeloid cells suppress not only NK and cytotoxic T lymphocyte (CTL) cytotoxicity but macrophage-mediated cytotoxicity as well. This review is focused on recent findings regarding strategies for inhibiting xenogenic rejection by macrophages. Disclosure: The authors have no conflicts of interest directly relevant to the content of this article. Funding: This work was supported by Grants-in Aid for Scientific Research, and Health and Labor Sciences Research Grants, Japan. Correspondence: Akira Maeda Division of Organ Transplantation, Department of Surgery, Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita, Osaka 565-0871, Phone: +81-6-6879-3755, email: ZUL06720@nifty.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Can mammalian target of rapamycin inhibitors replace mycophenolate in hypersensitized kidney transplant recipients? No abstract available

The causes of kidney allograft failure: more than allo-immunity. A viewpoint paper. Kidney allograft failure is a serious condition as it implies the need for re-initiation of dialysis with associated morbidity and mortality, reduced quality of life and higher economic cost. Despite improvements in short-term survival of kidney allografts, this progress was not matched in long-term graft survival. In this viewpoint paper, we summarize the available literature on the causes of kidney allograft failure, both early and late, both nonimmune and allo-immune, to gain better insight in the causes of graft failure. Such insight is necessary to better target therapies or take preventative measures, that improve long-term outcome after kidney transplantation. * These authors contributed equally The authors declare no conflicts of interest. Funding: MN is supported by the Seventh Framework Programme (FP7) of the European Commission, in the HEALTH.2012.1.4-1 theme (grant number 305499); The Research Foundation Flanders (F.W.O.) and Flanders Innovation and Entrepreneurship (Agentschap Innoveren en Ondernemen) of the Flemish Government (grant numbers IWT.2015.0199 and T004417N) and KU Leuven (grant number C32/17/049). EVL holds a fellowship grant (1143919N) from The Research Foundation Flanders (F.W.O.) and MN is senior clinical investigator of The Research Foundation Flanders (F.W.O.) (1844019N). Corresponding author: Maarten Naesens, MD, PhD, Department of Nephrology and Renal Transplantation, University Hospitals Leuven, Herestraat 49, 3000 Leuven, Belgium. Tel: +32 16 34 45 80; Fax: +32 16 34 45 99, Email: maarten.naesens@uzleuven.be Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Liver and Kidney Recipient Selection of HCV-Viremic Donors – Meeting Consensus Report from the 2019 Controversies in Transplantation The development of multiple highly effective and safe direct-acting antivirals to treat hepatitis C virus (HCV) has resulted in greater ease and confidence in managing HCV infection in transplant recipients that in turn, has impacted the solid organ transplant community as well. In the United States, the opioid epidemic has increased the number of overdose deaths with a concomitant increase in younger HCV viremic donors after brain death being identified. At the same time, a decrease in HCV viremic transplant candidates has led to a growing interest in exploring the use of HCV viremic liver and kidney donor allografts in HCV-negative recipients. To date, experience with the use of HCV viremic liver and kidney allografts in HCV-negative recipients is limited to a few small prospective research trials, case series, and case reports. There are also limited data on recipient and donor selection for HCV viremic liver and kidney allografts. In response to this rapidly changing landscape in the United States, experts in the field of viral hepatitis and liver and kidney transplantation convened a meeting to review current data on liver and kidney recipient selection and developed consensus opinions related specifically to recipient and donor selection of HCV viremic liver and kidney allografts. Dr. Burton and Pomfret were critically involved in the scientific organization of the meeting. All of the authors, except Drs. Burton and Pomfret participated in literature review and presentation of their findings at the meeting. All of the authors participated in the writing of the paper. Funding: No funding was received by any of the authors for this work. Corresponding author: James. R. Burton, Jr., MD, Associate Professor of Medicine, Department of Medicine, Division of Gastroenterology and Hepatology, Section Head, Hepatology, Medical Director of Liver Transplantation, University of Colorado Hospital, Anschutz Outpatient Pavilion, 7th Floor, B-154, 1635 Aurora Court, Aurora, CO, Phone: 720-848-2245, Fax: 720-848-2246, james.burton@cuanschutz.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Calcineurin inhibitor-free maintenance immunosuppression after heart transplantation – are we there yet? No abstract available

Commentary: Improving Patient Access to Liver Allografts Through a Mathematically Optimized Continuous Organ Distribution Model No abstract available

Cardiac Ventilation During Apnea Test No abstract available

TNFAIP8 deficiency exacerbates acute graft versus host disease in a murine model of allogeneic hematopoietic cell transplantation Background: Gastrointestinal acute graft-versus-host disease (aGVHD) occurring after allogeneic hematopoietic cell transplant (allo-HCT) is an alloreactive T cell- and inflammatory cytokine driven organ injury with epithelial apoptosis as one of its hallmark findings, and is associated with significant mortality. Tumor necrosis factor (TNF)-alpha-induced protein 8 (TNFAIP8 or TIPE) acts as a negative mediator of apoptosis via inhibition of caspase-3 activation, promotes cell proliferation and Tipe-/- deficiency is associated with increased inflammation. Methods: To evaluate the role of TIPE in acute GVHD, naive C57BL/6 and Tipe-/- C57BL/6 mice were conditioned with 1000cGy single dose total-body irradiation, followed by transplantation of 10 million bone marrow (BM) cells and 20 million splenocytes from either syngeneic C57BL/6 or allogeneic BALB/c donors. Results: Allo TIPE-deficient mice developed exacerbated gut GVHD compared to allo controls and had significantly decreased survival (6 weeks OS: 85% vs 37%; p<0.05), higher clinical GVHD scores, more profound weight loss, increased serum proinflammatory cytokines (IL-17A, TNF, IL-6, IFN-y). T cell infiltration into the ileum was increased; epithelial proliferation was decreased along with significantly higher levels of chemokines KC and MIG. Using BM chimeric experiments, TIPE was found to have a role in both hematopoietic and nonhematopoietic cells. Conclusions: Absence of TIPE results in excessive inflammation and tissue injury after allo HCT, supporting that TIPE confers immune homeostasis and has tissue-protective function during the development of gut GVHD, and may be a potential future target to prevent or treat this complication after allogeneic HCT. Disclosure: GCH and SP have received project-unrelated research funding from Takeda, Pharmacyclics and JAZZ Pharmaceuticals. GCH has advisory roles in the field of GVHD with Incyte and JAZZ Pharmaceuticals. Other authors declare no conflict of interest. Funding: This work has been funded by University of Kentucky, Lexington, Kentucky, USA. Corresponding author: Gerhard C. Hildebrandt, MD, FACP, Professor of Medicine, Division of Hematology & Blood and Marrow Transplantation, University of Kentucky, 800 Rose Street, CC404, Lexington, KY 40536-0093, 859 218- 4966 phone, 859 257-3531 fax, Email: gerhard.hildebrandt@uky.edu Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.