Toward Deciphering the Code of Pediatric Donor Glomerulopathy No abstract available

Delayed Implantation of Pumped Kidneys Decreases Renal Allograft Futility in Combined Liver-Kidney Transplantation Background: Combined liver-kidney transplantation (CLKT) improves survival for liver transplant recipients with renal dysfunction; however, the tenuous perioperative hemodynamic and metabolic milieu in high acuity CLKT recipients increases delayed graft function and kidney allograft failure. We sought to analyze whether delayed KT through pumping would improve kidney outcomes following CLKT. Methods: A retrospective analysis (UCLA [n=145], TMH [n=79]) was performed of all adults receiving CLKT at 2 high-volume transplant centers from February 2004 through January 2017, and recipients were analyzed for patient and allograft survival as well as renal outcomes following CLKT. Results: 63 patients (28.1%) underwent delayed implantation of pumped kidneys (dCLKT) and 161 patients (71.9%) received early implantation of nonpumped kidneys (eCLKT). Most recipients were high-acuity with median biologic MELD 35 for dCLKT and 34 for eCLKT (p=ns). Pretransplant, dCLKT had longer ICU stay, were more often intubated, and had greater vasopressor use. Despite this, dCLKT exhibited improved 1-, 3-, and 5-yr patient and kidney survival (p=0.02) and decreased length of stay (p=0.001), kidney allograft failure (p=0.012), and dialysis duration (p=0.031). This reduced kidney allograft futility (death or continued need for hemodialysis within 3 months posttransplant) for dCLKT (6.3%) compared with eCLKT (19.9%) (p=0.013). Conclusions: Delayed implantation of pumped kidneys is associated with improved patient and renal allograft survival and decreased hospital length of stay despite longer kidney cold ischemia. These data should inform the ethical debate as to the futility of performing CLKT in high-acuity recipients. * Indicates corresponding author FUNDING: We would like to thank the Houston Methodist Institution of Academic Medicine for their generous funding contributions. DISCLOSURE: The authors of this manuscript have no conflicts of interests to disclose as described by Transplantation. CORRESPONDING AUTHOR:: A. Osama Gaber, MD, J.C. Walter Jr. Distinguished Endowed Chair, Director, Houston Methodist J.C. Walter Jr. Transplant Center, Professor of Surgery, Weill Cornell Medical College, Vice Chair Administration & Faculty Affairs, Department of Surgery, 6550 Fannin Street, Suite 1661, Houston, TX 77030, Email: AOGaber@houstonmethodist.org Office: 713-441-6174, Fax: 713-790-6839 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

OUTCOMES OF PATIENTS SUSPENDED FROM THE NATIONAL KIDNEY TRANSPLANT WAITING LIST IN THE UNITED KINGDOM BETWEEN 2000 AND 2010. Background: In the UK, 1 in 3 patients on the National Kidney Transplant Waiting List (NKTWL) are suspended from the list at least once during their wait. The mortality of this large cohort of patients remains underreported and poorly described. Methods: We linked patient records from the UK Transplant Registry to mortality data from the Office of National Statistics and evaluated the impact of a clinically induced suspension event by estimating hazard ratios (HR) that compared mortality and graft survival between those who had experienced a suspension event and those who had not. Results: Between Jan 1, 2000, and Dec 31, 2010, 16.7% (2221/13 322) of all patients registered on the NKTWL were suspended. 48.0% (588/1225) of those who were suspended and who were never transplanted died, most often from cardiothoracic causes. A suspension event was associated with increased mortality from the time of listing (aHR: 1·79, 1·64-1·95) and from the time of transplantation (aHR: 1·20, 1.06-1.37, p=0005). Graft survival was also poorer in those who had been suspended (aHR: 1·13, 1·01-1·28, p=0·04). Conclusions: Patients suspended on the NKTWL have a significantly higher rate of mortality both on the waiting list and following transplantation. Earlier prioritisation of patients at risk of experiencing a suspension event may improve their outcomes. * Joint first authors Declaration of interests: The authors declare no competing interests. All authors have given final approval for this manuscript to be submitted to Transplantation. Correspondence: Mr Roberto Cacciola, Organ Donation and Transplantation, NHS Blood Transplant, Fox Den Road, Stoke Gifford, Bristol, UK: Roberto.cacciola@nhs.net, Tel No: 07789 864155 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Liver retransplantation associated with kidney transplantation for end stage liver graft disease and renal insufficiency: a morbid procedure on a unique subgroup of patients. Background: Chronic renal disease (CKD) jeopardizes the long-term outcomes of liver transplant recipients. In patients with end-stage liver graft disease and CKD, liver retransplantation associated with kidney transplantation (ReLT-KT) might be necessary. Yet, this specific subset of patients remains poorly described. Methods: Indications, perioperative characteristics, and short and long-term outcomes of patients undergoing ReLT-KT at 2 transplantation units from 1994 to 2012, were analyzed. Risk factors for postoperative mortality and long-term survivals were evaluated. Results: Among 3060 patients undergoing liver transplantation (LT), 45 (1.5%) underwent ReLT-KT. The proportion of ReLT-KT among LT recipients continuously grew throughout the study period from 0.3% to 2.4% (p<0.001). Median time from primary LT to ReLT-KT was 151.3 (7.5-282.9) months. The most frequent indications for liver retransplantation were recurrence of the primary liver disease and cholangitis in 15 (33.3%) cases each. CKD was related to calcineurin inhibitors toxicity in 38 (84.4%) cases. Twelve (26.7%) patients died postoperatively. D-MELD (donor age*recipients’ MELD) was associated with postoperative mortality (HR: 8.027; 95% CI: 2.387-18.223; p=0.026) and optimal cut-off value was 1039 (AUC: 0.801; p=0.002). Overall 1, 3 and 5 years survivals were 68.8%, 65.9% and 59.5%, respectively. D-MELD > 1039 was the only factor associated with poor survival (p=0.021). Conclusions: ReLT-KT is a highly morbid increasingly performed procedure. Refinements in the selection of grafts and transplant candidates are required in order to limit the postoperative mortality of these patients. Disclosure: The authors declare no conflicts of interest Funding: None Corresponding author:François Cauchy, Department of HPB and liver transplantation surgery, Hôpital Beaujon, 100, Boulevard du Général Leclerc, 92110, Clichy, France. Tel: + 33 (1) 40.87.58.95, E-mail: fafatoubib@gmail.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

DSA are associated with more graft injury, more fibrosis and upregulation of rejection associated transcripts in subclinical rejection. Background: Subclinical T cell-mediated rejection (subTCMR) is commonly found after liver transplantation and has a good short-term prognosis, even when it is left untreated. Donor-specific antibodies (DSA) are putatively associated with a worse prognosis for recipient and graft after liver transplantation. Methods: To assess the immune regulation in subTCMR grafts, gene expression of 93 transcripts for graft injury, tolerance and immune regulation was analyzed in 77 biopsies with “no histological rejection” (NHR; n=25), “clinical TCMR” (cTMCR; n=16) and subTCMR (n=36). In addition, all available subTCMR biopsies (n=71) were tested for DSA with bead assays. Results: SubTCMR showed heterogeneous and intermediate expression profiles of transcripts that were upregulated in cTCMR. Graft gene expression suggested a lower activation of effector lymphocytes and a higher activation of regulatory T cells in grafts with subTCMR compared to cTCMR. DSA positivity in subTCMR was associated with histological evidence of more severe graft inflammation and fibrosis. This more severe DSA+ associated graft injury in subTCMR was converged with an upregulation of cTCMR associated transcripts. In nonsupervised analysis DSA positive subTCMR mostly clustered together with cTCMR, while DSA negative subTCMR clustered together with NHR. Conclusion: T cell-mediated rejection seem to form a continuum of alloimmune activation. Although subTCMR exhibited less expression of TCMR associated transcript, DSA positivity in subTCMR was associated with an upregulation of rejection associated transcripts. The identification of DSA positive subclinical rejection might help to define patients with more inflammation in the graft and development of fibrosis. * equal senior authors Disclosure: The authors declare no conflicts of interest. Financial support: The work was supported by grants from the German Research Foundation (SFB738 project B4 and Z2), the Integrated Research Center Transplantation (IFB-Tx projects ISI5, ISI6, CBT3) funded by the German Federal Ministry of Education and Research (reference nos. 01EO0802 and 01EO1302). R.T. was supported by the Young Faculty Program of Hannover Medical School. Corresponding author email: Dr. Richard Taubert (MD), Hannover Medical School, Dept. Gastroenterology, Hepatology and Endocrinology, OE 6810, Geb. K11 01-1360, Carl Neuberg Street 1, 30625 Hannover, Germany. Tel.: +49-511-532-6995; Fax: +49-511-532-6998, taubert.richard@mh-hannover.de Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Spinal cord ischemia in pancreas transplantation: the UK experience Background: Spinal cord ischemia (SCI) is a rare but devastating condition that can occur in the perioperative period resulting in paraplegia. Although diabetes mellitus is a risk factor for SCI in other types of major surgery, SCI is not widely recognized in transplantation. The aim of this study was to quantify the risk of spinal cord ischemia in pancreatic transplantation. Methods: All UK pancreas transplant units were surveyed between 2017-2018. The risk of SCI in pancreas transplantation was estimated using the number of radiologically-confirmed cases relative to the number of pancreatic transplants from UK registry data during the same time period. Results: There have been 6 cases of spinal cord ischemia during pancreas transplantation since 2002. No aortic clamping occurred in any recipient. During or after surgery, all patients experienced episodes of hypotension (systolic blood pressure ≤90mmHg) prior to the onset of neurological symptoms. Epoprostenol, epidural anesthesia and postoperative hemodialysis may have contributed to systemic hypotension. The mainstay of early treatment for SCI for all cases was blood pressure control. Discussion: Based on these findings, there is approximately a 1:440 risk of spinal cord ischemia in pancreas transplantation. Hypotension appears to be a prominent risk factor. Strategies for mitigating the risk of spinal cord ischemia are discussed, drawing on evidence from thoraco-abdominal aortic aneurysm surgery. The risk of long-term neurological deficit should be discussed with prospective pancreas recipients given the potential impact on posttransplant quality of life. Funding: No funding was required for this study. Disclosure: The authors of this manuscript have no conflicts of interest in relation to this paper to disclose as described by the Transplantation. Correspondence information: Benedict Lyle Phillips, Department of Nephrology and Transplantation, Guy’s Hospital, Great Maze Pond, London, SE1 9RT, Email" benedict.phillips@nhs.net, Phone: 020 7188 1543 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Fluid intake post Renal Transplant; drink to thirst or drink to target: does it matter? No abstract available

Center-Related Bias in MELD Scores Within a Liver Transplant UNOS Region: A Call for Standardization Background: MELD score-based liver transplant allocation was implemented as a fair and objective measure to prioritize patients based upon disease severity. Accuracy and reproducibility of MELD is an essential assumption to ensure fairness in organ access. We hypothesized that variability or bias in laboratory methodology between centers could alter allocation scores for individuals on the transplant waiting list. Methods: Aliquots of 30 patient serum samples were analyzed for creatinine, bilirubin, and sodium in all transplant centers within United Network for Organ Sharing (UNOS) region 9. Descriptive statistics, intraclass correlation coefficients (ICC), and linear mixed effects regression were used to determine the relationship between center, bilirubin and calculated MELD-Na. Results: The mean MELD-Na score per sample ranged from 14 to 38. The mean range in MELD-Na per sample was 3 points, but 30% of samples had a range of 4-6 points. Correlation plots and intraclass correlation coefficient analysis confirmed bilirubin interfered with creatinine, with worsening agreement in creatinine at high bilirubin levels. Center and bilirubin were independently associated with creatinine reported in mixed effects models. Unbiased hierarchical clustering suggested samples from specific centers have consistently higher creatinine and MELD-Na values. Conclusions: Despite implementation of creatinine standardization, centers within one UNOS region report clinically significant differences in MELD-Na on an identical sample, with differences of up to 6 points in high MELD-Na patients. The bias in MELD-Na scores based upon center choice within a region should be addressed in the current efforts to eliminate disparities in liver transplant access. Disclosures:Joshua Hayden: honoraria and research support from Roche Diagnostics Funding:None Corresponding Author:Elizabeth Verna, MD, MSc, Assistant Professor of Medicine, Director of Clinical Research, Transplant Clinical Research Center, Center for Liver Disease and Transplantation, Division of Digestive and Liver Diseases, Columbia University College of Physicians and Surgeons, email: ev77@columbia.edu, office: 212-305-0914, fax: 212-305-0914 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Nanotechnology Applications in Transplantation Medicine A recent technological advance that shows promise for applications in healthcare, including transplantation medicine, is the implementation of nanoparticles. Nanoparticles can be composed of a variety of organic or inorganic materials and confer many advantages over conventional treatments available, such as low toxicity, low effective dosage required, and a high degree of manipulability. Though also used for imaging and diagnostics, nanoparticles’ utility as a drug or genetic delivery system is of particular interest in transplantation medicine. Currently, researchers are exploring options to integrate nanoparticles into both diagnostics or therapy for both grafts ex-situ prior to transplantation and for patients following transplantation. These studies have demonstrated that nanoparticles can mitigate damage to organs and patients through a large variety of mechanisms - ranging from the induction of cellular genetic changes to the enhancement of immunosuppressive drug delivery. Specifically, with the advent of machine perfusion preservation ex-vivo, treatment of the graft became a very attractive approach and nanoparticles have great potential. However, before nanoparticles can be translated into clinical use, their short-term and long-term toxicity must be thoroughly characterized, especially with regards to their interactions with other biological molecules present in the human body. Financial Disclosure: The authors declare no funding was received for this study. Disclosure: The authors declare no conflict of interest. Corresponding author: Paulo N. Martins MD, PhD, FAST, FEBS, FACS, Associate Prof. of Surgery, Dept of Surgery, Transplant Division, University of Massachusetts, University Campus, 6th Floor, Rm: S6-743, 55 Lake Ave, Worcester-MA 01655, Tel: 508-334-2023 Fax 508-856-1102, Email: paulo.martins@umassmemorial.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Avoiding dual graft loss in simultaneous liver retransplantation and primary kidney transplantation No abstract available