Comparing glycaemic benefits of active versus passive lifestyle intervention in kidney allograft recipients (CAVIAR): a randomised controlled trial Background. New-onset diabetes is common after kidney transplantation but the benefit of lifestyle intervention to improve glucose metabolism post transplantation is unproven. Methods. We conducted a single-center, randomised controlled trial involving 130 nondiabetic kidney transplant recipients with stable function between 3-24 months post transplantation. Participants were randomly assigned in a 1:1 ratio to receive active intervention (lifestyle advice delivered by renal dietitians using behaviour change techniques) versus passive intervention (leaflet advice alone). Primary outcome was six-month change in insulin secretion, insulin sensitivity and disposition index. Secondary outcomes included patient-reported outcomes, cardio-metabolic parameters, clinical outcomes and safety endpoints. Results. Between August 17th 2015 and December 18th 2017, 130 individuals were recruited of whom 103 completed the study (drop-out rate 20.8%). Active versus passive intervention was not associated with any change in glucose metabolism; insulin secretion (mean difference -446 [95% CI -3184 to 2292], p=0.748), insulin sensitivity (mean difference -0.45 [95% CI -1.34 to 0.44], p=0.319) or disposition index (mean difference -940 [95% CI -5655 to 3775], p=0.693). Clinically, active versus passive lifestyle intervention resulted in reduced incidence of post transplantation diabetes (7.6% versus 15.6% respectively, p=0.123), reduction in fat mass (mean difference -1.537kg [-2.947 to -0.127], p=0.033) and improvement in weight (mean difference -2.47kg [-4.01 to -0.92], p=0.002). No serious adverse events were noted. Conclusions. Active lifestyle intervention led by renal dietitians did not improve surrogate markers of glucose metabolism. Further investigation is warranted to determine if clinical outcomes can be improved using this methodology. Trial Registration Registered with clinicaltrials.org registry (identifier; NCT02233491). Disclosure: The authors have no relevant disclosures to declare. Funding: This study was supported by grants from the European Foundation for the Study of Diabetes and the British Renal Society/Kidney Care UK. Corresponding author contact information. Dr. Adnan Sharif, Department of Nephrology and Transplantation, Queen Elizabeth Hospital, Edgbaston, Birmingham, B15 2GW, United Kingdom. Phone: (0121 371 5861), Fax: (0121 472 4942), Email: adnan.sharif@uhb.nhs.uk. Orchid ID: 0000-0002-7586-9136 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Multiple listings: Good for a few, but no solution for the organ shortage No abstract available

Optimizing allocation of older donors in liver transplantation: the objectives of allocation policies also matter No abstract available

Multiple regional listing increases liver transplant rates for those with MELD score less than 15 TPA-2019-0259R2 Clean Copy Background: Multiple listing (ML) at more than one transplant center is one mechanism to combat the geographic disparities in liver transplantation (LT) rates. The objective of our study was to determine the impact of multiple listing on LT rates. Patients & Methods: We examined the UNOS database from 2002 to 2016 after excluding those listed for multiple-organs, hepatocellular carcinoma or living donor LT. The waitlist mortality and LT rates for the ML groups and the single listed (SL) group were compared after stratifying patients by the MELD with a cut-off at 15 (<15 and ≤15). Results: Of the 83,935 listed during the study period, 80,351 were listed in a single center (SL group), and 3,584 were listed in more than one center (ML group). Of the ML groups, 2,028 (2.4%) were listed at multiple donor service areas but within the same region (ML-SR) and 1,556 (1.9%) listed in different regions (ML-DR). The median MELD at LT was 20, 21 and 24 for ML-DR, ML-SR and SL groups respectively (p=0.001). Although the probability of receiving LT was significantly higher for the ML groups relative to the SL group for both MELD groups (<15 and ≥15), the impact was highest for ML-DR group. At MELD score < 15, the probability of LT was 72% for ML-DR, 38% for ML-SR and 32% for SL groups. At MELD score ≥15, the probability of LT was 79% for ML-DR, 67% for ML-SR and 61% for SL groups. Conclusion: Multiple listing appeared to considerably improve a patient's chance of receiving LT and survival with the highest benefit for those with low MELD scores (<15) listed at multiple regions. Contribution of authors: SB contributed to the study concept. PT and SB drafted the manuscript study design, analysis and interpretation of data. YS did the statistical analysis. RB and JL contributed to the critical revision of manuscript Funding: None Conflict of Interests: None Corresponding author: Paul J. Thuluvath, MD., FAASLD, FRCP., Institute of DigestivS2264e Health & Liver Diseases, Mercy Medical Center, Baltimore MD 21202 , Tel: 410 332 9308, Email: thuluvath@gmail.com Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Differential Influence of Donor Age Depending on the Indication for Liver Transplantation – A Collaborative Transplant Study Report Background. Despite steadily increasing donor age, there are no general guidelines for the use of organs from elderly donors in liver transplantation. This study focuses on identifying the recipients who are less affected from an old-donor organ graft and conversely in whom a rather unfavorable outcome is expected due to high donor age. Methods. 48,261 adult liver transplantations, performed between 2000 and 2017 and reported to the Collaborative Transplant Study, were analyzed. Results. The proportion of ≥ 65-year-old donors has risen to more than 33% in recent years. The donor age has an approximately linear influence on graft survival. On average, each year’s rise in the donor age was associated with a 0.9% increase in the risk of graft loss, hazard ratio (HR) 1.009, P < 0.001. The impact of donor age was “strong” in patients with hepatitis C-related cirrhosis (HR 1.013, P < 0.001), “substantial” in patients with alcoholic cirrhosis (HR 1.007, P < 0.001), and “rather weak” in patients with hepatocellular carcinoma (HCC) (HR 1.003, P = 0.038). The increase in the risk of graft loss per year rise in donor age was 1.4% for 18- to 49-year-olds, 1.0% for middle-aged, and only 0.4% for ≥ 60-year-old recipients (all P < 0.001). Conclusions. Consequently, older recipients and especially patients with HCC seem to be less affected by an increased donor age, whereas the donor age is an important factor in all other patient groups. Disclosure: The authors of this manuscript have no conflicts of interest to disclose. Funding: The study received no external funding. Corresponding author Philipp Houben, MD, Department of General, Visceral, and Transplant Surgery, Heidelberg University Hospital Im Neuenheimer Feld 11069120 Heidelberg, Germany. Telephone:+49 6221 56-6111, Fax:+49 6221 64215, Email:philipp.houben@med.uni-heidelberg.de Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Too Much, Too Little, or Just Right? The Importance of Allograft Portal Flow in Deceased Donor Liver Transplantation Background. While portal flow (PF) plays an important role in determining graft outcomes in living donor liver transplantation, its impact in deceased donor whole liver transplantation (DDLT) is unclear. The aim of this study was to investigate the correlations between graft PF and graft outcomes in DDLT. Methods. We retrospectively investigated 1,001 patients who underwent DDLT between January 2007 and June 2017 at our institution. The patients were divided into three groups according to hazard ratio for one-year graft loss at each PF value, which was standardized with graft weight. Graft and recipient outcomes were compared between the groups. Results. The low-PF group (PF < 65 mL/min/100g, n = 210, P = 0.011) and the high-PF group (PF > 155 mL/min/100g, n = 159, P = 0.018) showed significantly poorer one-year graft survival compared with the intermediate-PF group (PF > 65 mL/min/100g and < 155 mL/min/100g, n = 632). The patients in the low-PF group had severe reperfusion injury and were more frequently complicated with primary nonfunction (P = 0.013) and early allograft dysfunction (P < 0.001) compared with the other groups. In contrast, the patients in the high-PF group had milder reperfusion injury, but had lower intraoperative hepatic artery flow with higher incidence of hepatic artery thrombosis (P = 0.043) and biliary complication (P = 0.041) compared with the other groups. Conclusions. These results suggest that intraoperative PF plays an important role in determining early graft outcomes after DDLT. Disclosure: The authors declare no conflicts of interest. Study findings were presented in 2019 at the Rising Star Plenary Session of the ILTS 25th Annual Congress, Toronto, Canada, and in 2019 at the American Transplant Congress, Boston, MA Reprints and Corresponding to: Koji Hashimoto, M.D., Ph.D. Department of General Surgery, Digestive Disease & Surgery Institute, Cleveland Clinic, 9500 Euclid Ave, A100, Cleveland, OH, 44195 , Telephone: 216-445-0753, Fax: 216-444-9357, E-mail: hashimk@ccf.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Renal Protection Against Ischemia Perfusion Injury: Hemoglobin Based Oxygen Carrier-201 vs. Blood as an Oxygen Carrier in Ex vivo Subnormothermic Machine Perfusion Background: The optimal method of oxygen delivery to donor kidneys during ex vivo machine perfusion has not been established. We have recently reported the beneficial effects of subnormothermic (22°C) blood perfusion in the preservation of porcine DCD kidneys. Since using blood as a clinical perfusate has limitations including matching availability and potential presence of pathogen, we sought to assess hemoglobin-based oxygen carrier, HBOC-201 in oxygen delivery to the kidney for renal protection. Methods: Pig kidneys (n=5) were procured following 30 min of warm in situ ischemia by cross-clamping the renal arteries. Organs were flushed with HTK solution and subjected to static cold storage or pulsatile perfusion with an RM3 pump at 22°C for 4h with HBOC-201 and blood. Thereafter, kidneys were re-perfused with normothermic (37°C) oxygenated blood for 4h. Blood and urine were subjected to biochemical analysis. Total urine output, urinary protein, albumin/creatinine ratio, flow rate, resistance were measured. Acute tubular necrosis, apoptosis, urinary kidney damage markers (KIM-1, NGAL) and IL6 were also assessed. Results: HBOC-201 achieved tissues oxygen saturation equivalent to blood. Furthermore, upon reperfusion, HBOC-201 treated kidneys had similar renal blood flow and function compared with blood-treated kidneys. Histologically, HBOC-201 and blood perfused kidneys had vastly reduced ATN scores and degrees of TUNEL staining vs. kidneys treated with cold storage. Urinary damage markers and IL6 levels were similarly reduced by both blood and HBOC-201. Conclusion: HBOC-201 is an excellent alternative to blood as an oxygen carrying molecule in an ex vivo subnormothermic machine perfusion platform in kidneys. Conflicts of Interest. The authors declared no funding or conflicts interests. R.N.B. participated in the performance of the research, data analysis, construction of figures and article writing. M.R.M. and A.R. participated in kidney perfusion and preparation of perfusion circuit. S.V.P, S.A, and R.A.O. participated in surgical procedures. Q. S., S. J., and L.J. participated in sample collection, data analysis. A.S. participated in article editing. P.P.L participated in the intellectual conception of project, extensive literature review, partial article writing, editing and final approval of the article. DISCLOSURE: The authors declare that they have no competing interest or funding. Correspondence: Patrick P.W. Luke, Department of Surgery, Division of Urology, Western University, London Health Sciences Centre, 339 Windermere Road, London, Ontario, Canada N6A 5A5. Tel: 519-685-8500 x 33180; Email: Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Offspring vs. Non Offspring to Parent Living Donor Liver Transplantation: Does Donor Relationship Matter? INTRODUCTION: Offspring (donor) to parent (recipient) transplant is the most common form of living donor liver transplant in the United States. In kidney transplantation, it has been suggested that female recipients of offspring living donor kidney allografts have inferior outcomes. It is unknown whether such a phenomenon also occurs following living donor liver transplantation. METHODS: A retrospective analysis was completed of recipients of a living donor liver transplant from January 1998 to January 2018 in the OPTN/UNOS database. Patients were grouped as having received a living donor liver allograft from either an offspring or a nonoffspring, with exactly three HLA matches, as would be expected between an offspring and parent. Graft and patient survival were analyzed using Cox proportional hazards modeling. RESULTS: 279 offspring to parent and 241 nonoffspring donor liver transplants were included in the analysis. Female recipients of offspring liver allografts had both inferior 10-year graft (52% vs 72%, P<0.001) and patient survival (52% vs 81%, P<0.001) compared with female recipients of nonoffspring allografts. No such difference in outcomes was discovered amongst male recipients. A stratified analysis of sex of offspring donors to female recipients demonstrated that donor male gender was associated with graft failure (HR=2.87, P=0.04) and mortality (HR=3.89, P=0.03). Again, this association was not seen with male recipients. CONCLUSIONS: Among female recipients, offspring to parent living donor liver transplantation yields inferior long-term graft and patient survival. Furthermore, among offspring donors, male sex was strongly associated with inferior outcomes. These findings have significant implications for donor selection. Conflict of Interest: The authors declare no conflicts of interest. Financial Disclosures: The authors declare no financial disclosures Corresponding Author Name: Rashikh A Choudhury, Address: 2749 Walnut St, Unit 424, Denver, CO, 80205, Email: Rashikh.choudhury@ucdenver.edu, Phone: 513.375.2611 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

Outcomes of Conversion from Calcineurin Inhibitor to Belatacept-Based Immunosuppression in HLA Sensitized Kidney Transplant Recipients Background: The efficacy and safety of belatacept when converted from calcineurin inhibitors (CNI) in HLA-sensitized kidney transplant recipients has not been established. Methods: The study included 108 kidney transplant recipients converted from CNI to belatacept between 7/1/12 to 9/30/17. Rejection-free, patient, and graft survival over 5 years follow-up were compared between HLA-sensitized (HS) and non-HLA sensitized (non-HS) recipients using the Kaplan-Meier product-limit method. The eGFR slope post conversion was compared using linear mixed effects models. Results: There were 29 HS and 79 non-HS recipients included. Rejections after conversion were mostly cell-mediated. There was no difference in rejection-free survival (log-rank p=0.30; at 5 years, HS: 82%; non-HS: 84.6%); however, rejection-free survival was lower among HS recipients converted within the first year post transplant compared to non-HS recipients (log-rank p=0.03; at 5 years, HS: 55.6%; non-HS: 75.0%) . There was no difference in patient survival (log-rank p=0.75; at 5 years, HS: 85.7%, non-HS: 83.7%;) or graft survival (log-rank p=0.17; at 5 years, HS: 78.5%, non-HS: 89.8%) in the two groups. On average, eGFR slope improved post conversion in non-HS [0.28 ml/min/1.73 m2/year (0.03 to 0.53)] but declined in HS recipients [-0.44ml/min/1.73 m2/year (-0.85 to -0.03)]. Conclusions: There was no difference in rejection-free, patient, or graft survival after conversion to belatacept over 5 years among HS and non-HS recipients. However, rejection-free survival was lower in HS recipients converted to belatacept within the first year post transplant. Conversion from CNI to belatacept should be done cautiously in high immunologic risk patients. Disclosure: The authors declare no conflicts of interest. Funding source: None Corresponding author: Supreet Sethi, M.D., Comprehensive Transplant Center, Cedars Sinai Medical Center, 8900 Beverly Boulevard, 2nd Floor Room 232, West Hollywood, CA 90048, Email address: supreet.sethi@cshs.org Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.

A Cautionary Tale: Declining Renal Function Following Acute Rejection Post Conversion From Calcineurin Inhibitor to Belatacept in HLA Sensitized Individuals in the First Post Transplant Year No abstract available