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This review highlights the salient data of the psychosocial concerns that influence outcomes of bariatric surgery and organ transplantation.Bariatric surgery has emerged as an important intervention with data supporting substantial and sustained weight loss, enhanced quality of life, remission of obesity-related medical comorbidities, and improved long-term patient and graft survival in transplant patients. Depression, suicide, anxiety, posttraumatic stress disorder, alcohol use, adherence, and psychopharmacology considerations can influence outcomes of both these surgeries.Obesity is increasingly prevalent among patients pursuing transplantation surgery, and it is often a factor in why a patient needs a transplant. However, obesity can be a barrier to receiving a transplant, with many centers implementing BMI criteria for surgery. Furthermore, obesity and obesity-related comorbidities after transplant can cause poor outcomes. In this context, many transplant centers have created programs that incorporate interventions (such as bariatric surgery) that target obesity in transplant candidates. A presurgery psychosocial assessment is an integral (and required) part of the process towards receiving a bariatric surgery and/or a transplantation surgery. When conducting a dual (bariatric and transplantation surgery) psychosocial assessment, it is prudent to understand the overlap and differentiation of specific psychosocial components that influence outcomes in these procedures.

Burnout among surgeons has been attributed to increased workload and decreased autonomy. Although prior studies have examined burnout among transplant surgeons, no studies have evaluated burnout in abdominal transplant surgery fellows. The objective of our study was to identify predictors of burnout and understand its impact on personal and patient care during fellowship. A survey was sent to all abdominal transplant surgery fellows in an American Society of Transplant Surgeons-accredited fellowship. The response rate was 59.2% (n = 77) and 22.7% (n = 17) of fellows met criteria for burnout. Fellows with lower grit scores were more likely to exhibit burnout compared with fellows with higher scores (3.6 vs 4.0, P = .026). Those with burnout were more likely to work >100 hours per week (58.8% vs 27.6%, P = .023), have severe work-related stress (58.8% vs 22.4%, P = .010), consider quitting fellowship (94.1% vs 20.7%, P < .001), or make a medical error (35.3% vs 5.2%, P = .003). This national analysis of abdominal transplant fellows found that burnout rates are relatively low, but few fellows engage in self-care. Personal and program-related factors attribute to burnout and it has unacceptable effects on patient care. Transplant societies and fellowship programs should develop interventions to give fellows tools to prevent and combat burnout.

Because of underutilization of liver allografts, our center previously showed that hepatitis C virus (HCV) antibody-positive/nucleic acid test (NAT)-negative livers when transplanted into HCV nonviremic recipients were safe with a 10% risk of HCV transmission. Herein, we present our single-center prospective experience of using HCV NAT+ liver allografts transplanted into HCV NAT- recipients. An institutional review board-approved matched cohort study was conducted examining post- liver transplantation (LT) outcomes of HCV- patients who received HCV NAT+ organs (treatment group) compared with matched recipients with HCV NAT- organs (matched comparator group) between June 2018 to October 2019. The primary endpoint was success of HCV treatment and elimination of HCV infection. The secondary outcomes included the 30-day and 1-year graft and patient survival as well as perioperative complications. There were 32 recipients enrolled into each group. Because of 1 death in the index admission, 30/31 patients (97%) were given HCV treatment at a median starting time of 47 days (18-140 days) after LT. A total of 19 (63%) patients achieved sustained virological response at week 12 (SVR12). Another 6 patients achieved end-of-treatment response, while 5 remained on therapy and 1 is yet to start treatment. No HCV treatment failure has been noted. There were no differences in 30-day and 1-year graft and patient survival, length of hospital stay, biliary or vascular complications, or cytomegalovirus viremia between the 2 groups. In this interim analysis of a matched cohort study, which is the first and largest study to date, the patients who received the HCV NAT+ organs had similar outcomes regarding graft function, patient survival, and post-LT complications.

Simultaneous liver-kidney transplantation (SLKT) is indicated for patients with end-stage liver disease (ESLD) and concurrent renal insufficiency. En bloc SLKT is an alternative to traditional separate implantations, but studies comparing the two techniques are limited. The en bloc technique maintains renal outflow via donor infrahepatic vena cava and inflow via anastomosis of donor renal artery to donor splenic artery. Comparison of recipients of en bloc (n = 17) vs traditional (n = 17) SLKT between 2013 and 2017 was performed. Recipient demographics and comorbidities were similar. More recipients of traditional SLKT were dialysis dependent (82.4% vs 41.2%, P = .01) with lower baseline pretransplant eGFR (14 vs 18, P = .01). En bloc SLKT was associated with shorter kidney cold ischemia time (341 vs 533 minutes, P < .01) and operative time (374 vs 511 minutes, P < .01). Two en bloc patients underwent reoperation for kidney allograft inflow issues due to kinking and renal steal. Early kidney allograft dysfunction (23.5% in both groups), 1-year kidney graft survival (88.2% vs 82.4%, P = 1.0), and posttransplantation eGFR were similar between groups. In our experience, the en bloc SLKT technique is safe and feasible, with comparable outcomes to the traditional method.

Morbid obesity is a barrier to kidney transplant in patients with end-stage renal disease (ESRD). Laparoscopic sleeve gastrectomy (SG) is an increasingly considered intervention, but the safety and long-term outcomes are uncertain. We reviewed prospectively collected data on patients with ESRD and chronic kidney disease (CKD) undergoing SG from 2011 to 2018. There were 198 patients with ESRD and 45 patients with CKD (stages 1-4) who met National Institutes of Health guidelines for bariatric surgery and underwent SG; 72% and 48% achieved a body mass index of ≤ 40 and ≤ 35 kg/m2 , respectively. The mean percentages of total weight loss and excess weight loss were 18.9 ± 10.8% and 38.2 ± 20.3%, respectively. SG reduced hypertension (85.8% vs 52.1%), decreased antihypertensive medication use (1.6 vs 1.0) (P < .01 each), and reduced incidence of diabetes (59.6% vs 32.5%, P < .01). Of the 71 patients with ESRD who achieved a body mass index of ≤ 40 kg/m2 , 45 were waitlisted and received a kidney transplant, whereas 10 remain on the waitlist. Mortality rate after SG was 1.8 per 100 patient-years, compared with 7.3 for non-SG. Patients with stage 3a or 3b CKD exhibited improved glomerular filtration rate (43.5 vs 58.4 mL/min, P = .01). In conclusion, SG safely improves transplant candidacy while providing significant, sustainable effects on weight loss, reducing medical comorbidities, and possibly improving renal function in stage 3 patients.

Morbid obesity serves as a barrier to kidney transplantation (KT) due to potential suboptimal posttransplant outcomes. Laparoscopic sleeve gastrectomy (LSG) has previously been shown to improve transplant eligibility through weight loss.We aimed to examine the role LSG plays in improving patient outcomes postrenal transplantation, including possible impact on new-onset diabetes after transplant (NODAT).University Hospital.A single-center analysis was performed identifying all patients who underwent KT after LSG from 2011 to 2017 (n = 41). Exclusion criteria included type I diabetes and previous pancreas transplantation. NODAT was defined as a new insulin requirement after KT. Delayed graft function was defined as need for dialysis within the first week after KT. Mean posttransplant follow-up period was 22 months.Forty-one patients underwent KT after LSG after median time of 16 months. Median age of postLSG patients undergoing KT was 56.0 years at time of KT. Average body mass index decreased by 9 from the time of LSG to KT, and no patients regained weight at 1-year follow-up. After LSG, the number of patients with hypertension (85.4% versus 48.5%) and the number of antihypertensive medications used decreased significantly (1.6 versus .6) at time of KT (P.001 each). At 1-year follow-up, the improvement in hypertension persisted (51.2% versus 48.5%, P = nonsignificant). The average insulin regimen decreased from 33.0 ± 51.6 to 11.7 ± 21.5 units at KT (P.001). This improvement also persisted at 1-year follow-up (11.9 versus 11.7 units, P = nonsignificant). Zero patients suffered NODAT over the follow-up period (versus institutional rate of NODAT at 15.8%). One patient developed delayed graft function (2.4%, versus institutional rate of 13.3%). After 1 year postKT, there was 1 graft loss (2.4%) and no mortality.This is the largest reported series of KT after planned LSG in morbidly obese patients. Our results confirm excellent posttransplant outcomes among patients who otherwise would have been denied KT eligibility.

Breakthroughs in Hepatitis C virus (HCV) treatment and rising rates of intravenous drug use have led to an increase in the number of organ donors that are HCV antibody positive but serum nucleic acid test (NAT) negative. The risk of HCV transmission from the liver grafts of these donors to recipients is unknown. To estimate the incidence of HCV transmission, we prospectively followed 26 consecutive HCV antibody (n=25) or NAT (n =1) negative transplant recipients who received a liver graft from donors that were HCV antibody positive but serum NAT negative between March 2016 and March 2017. HCV transmission was considered to have occurred if recipients exhibited a positive HCV-polymerase chain reaction test by 3 months following transplantation. Drug overdose was listed as the cause of death in 15 (60%) of the donors. One recipient died eighteen days after transplantation from primary graft non-function and was excluded. Of the remaining 25 recipients, HCV transmission occurred in 4 (16%), at a median follow up of 11 months, all from donors who died of drug overdose. Three of these patients were treated with direct acting antiviral therapy, with two achieving a sustained virologic response and one an end-of-treatment response. One patient with HCV transmission died after a complicated post-operative course and did not receive antiviral therapy. Conclusions: In this prospective cohort of non-HCV liver recipients receiving grafts from HCV antibody positive/NAT negative donors, the incidence of HCV transmission was 16%, with the highest risk conferred by donors who died of drug overdose. Given the availability of safe and highly effective antiviral therapies, use of such organs could be considered to expand the donor pool. This article is protected by copyright. All rights reserved.

The CD44 gene encodes several protein isoforms due to alternative splicing and post translational modifications. Given that CD44 variant isoform 9 (CD44v9) is expressed within Spasmolytic Polypeptide/TFF2-Expressing Metaplasia (SPEM) glands during repair, CD44v9 may be play a funcitonal role during the process of regeneration of the gastric epithelium. Here we hypothesize that CD44v9 marks a regenerative cell lineage responsive to infiltrating macrophages during regeneration of the gastric epithelium. Ulcers were induced in CD44-deficient (CD44KO) and C57BL/6 (BL6) mice by a localized application of acetic acid to the serosal surface of the stomach. Gastric organoids expressing CD44v9 were derived from mouse stomachs and transplanted at the ulcer site of CD44KO mice. Ulcers, CD44v9 expression, proliferation and histology were measured 1, 3, 5 and 7-days post-injury. Human-derived gastric organoids were generated from stomach tissue collected from elderly (>55 years) or young (14-20 years) patients. Organoids were transplanted into the stomachs of NOD scid gamma (NSG) mice at the site of injury. Gastric injury was induced in NRG-SGM3 (NRGS) mice harboring human-derived immune cells (hnNRGS) and the immune profile anlayzed by CyTOF. CD44v9 expression emerged within regenerating glands the ulcer margin in response to injury. While ulcers in BL6 mice healed within 7-days post-injury, CD44KO mice exhibited loss of repair and epithelial regeneration. Ulcer healing was promoted in CD44KO mice by transplanted CD55v9-expressing gastric organoids. NSG mice exhibited loss of CD44v9 expression and gastric repair. Transplantation of human-derived gastric organoids from young, but not aged stomachs promoted repair in NSG mouse stomachs in response to injury. Finally, compared to NRGS mice, huNRGS animals exhibited reduced ulcer sizes, an infiltration of human CD162+ macrophages and an emergence of CD44v9 expression in SPEM. Thus, during repair of the gastic epithelium CD44v9 emerges within a regenerative cell lineage that coincides with macrophage inflitration within the injured mucosa. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Reduction in donor-specific antibody (DSA) has been associated with improved renal allograft survival after antibody-mediated rejection (AMR). These observations have not been separately analyzed for early and late AMR and mixed acute rejection (MAR). The purpose of this study was to evaluate long-term responses to proteasome inhibitor-based therapy for 4 rejection phenotypes and to determine factors that predict allograft survival.Retrospective cohort study evaluating renal transplant recipients with first AMR episodes treated with proteasome inhibitor-based therapy from January 2005 to July 2015.A total of 108 patients were included in the analysis. Immunodominant DSA reduction at 14 days differed significantly (early AMR 79.6%, early MAR 54.7%, late AMR 23.4%, late MAR 21.1%, P0.001). Death-censored graft survival (DCGS) differed at 3 years postrejection (early AMR 88.3% versus early MAR 77.8% versus late AMR 56.7% versus late MAR 54.9%, P = 0.02). Multivariate analysis revealed that immunodominant DSA reduction50% at 14 days was associated with improved DCGS (odds ratio, 0.12, 95% CI, 0.02-0.52, P = 0.01).In summary, significant differences exist across rejection phenotypes with respect to histological and DSA responses. The data suggest that DSA reduction may be associated with improved DCGS in both early and late AMR.

The increasing obesity epidemic has major implications in the realm of transplantation. Patients with obesity face barriers in access to transplant and unique challenges in perioperative and postoperative outcomes. Because of comorbidities associated with obesity, along with the underlying end-stage organ disease leading to transplant candidacy, these patients may not even be referred for transplant evaluation, much less be waitlisted or actually undergo transplant. However, the use of bariatric surgery in this population can help optimize the transplant candidacy of patients with obesity and end-stage organ disease and improve perioperative and postoperative outcomes. We review the impact of obesity on kidney, liver, and cardiothoracic transplant candidates and recipients and explore potential interventions to address obesity in these populations.

Obesity has become an epidemic in the United States over the past decade, and recent studies have shown this trend in the liver transplantation (LT) population. These patients may be candidates for laparoscopic sleeve gastrectomy (LSG) to promote significant and sustained weight loss to prevent recurrence of nonalcoholic steatohepatitis. However, safety remains a concern, and efficacy in this setting is uncertain. A single-institution database from 2014 to 2018 was queried for patients undergoing LSG following LT. The selection criteria for surgery were consistent with National Institutes of Health guidelines, and patients were at least 6 months after LT. A total of 15 patients (median age, 59.0 years; Caucasian, 86.7%; and female, 60%) underwent LSG following LT. Median time from LT to LSG was 2.2 years with a median follow-up period of 2.6 years. The median hospital length of stay (LOS) was 2 days after LSG. Mortality and rate of liver allograft rejection was 0, and there was 1 postoperative complication (a surgical site infection). Following LSG, body mass index (BMI) decreased from 42.7 to 35.9 kg/m2 (P < 0.01), and in 12 patients with at least 1 year of follow-up, the total body weight loss was 20.6%. Following LSG in patients with diabetes, the median daily insulin requirements decreased from 98 (49-118) to 0 (0-29) units/day (P = 0.02), and 60% discontinued insulin. Post-LT patients had a similar decrease in BMI and reduction in comorbidities at 1 year compared with a matched non-LT patient cohort. In the largest patient series to date, we show that LSG following LT is safe, effective, and does not increase the incidence of liver allograft rejection. Larger longer-term studies are needed to confirm underlying metabolic changes following LSG.

A growing number of renal transplant recipients have a body mass index ≥40. While previous studies have shown that patient and graft survival are significantly decreased in renal transplant recipients with body mass indexes ≥40, less is known about perioperative outcomes and resource utilization in morbidly obese patients. We aimed to analyze the effects of morbid obesity on these parameters in renal transplant.Using a linkage between the Scientific Registry of Transplant Recipients and the databases of the University HealthSystem Consortium, we identified 29,728 adult renal transplant recipients and divided them into 2 cohorts based on body mass index (40 vs ≥40 kg/mBody mass index ≥40 recipients incurred greater direct costs ($84,075 vs $79,580, P .01), index admission costs ($91,169 vs $86,141, P .01), readmission costs ($5,306 vs $4,596, P = .01), and combined costs ($99,590 vs $93,939, P .001). Thirty-day readmission rates were also greater among body mass index ≥40 recipients (33.92% vs 26.9%, P .01). Morbid obesity was not predictive of stay (odds ratio 1.01, P = .75).Morbidly obese renal transplant recipients incur greater costs and readmission rates compared with nonobese patients. Recognition of increased resource utilization should be accompanied by appropriate, risk-adjustment reimbursement.

Context: Obesity has been reported as risk factor for reduced posttransplant graft and patient survival and increased delayed graft function (DGF). Objective: The purpose of this work is to analyze the effect of body mass index (BMI) on defined transplant outcomes in patients transplanted under defined guidelines in a kidney transplant program. Design: Review of a prospectively collected database in renal transplant recipients receiving rabbit antithymocyte globulin induction, mycophenolate mofetil, tacrolimus, and early corticosteroid withdrawal between 2001 and 2011. Setting: This review was conducted in a single abdominal transplant program in the United States. Main Outcome Measures: Primary outcome was death-censored graft survival categorized by posttransplant body mass groups. Secondary outcomes included DGF as well as patient survival. Results: Four hundred sixty seven patients were identified. No difference was observed in graft survival or DGF between BMI groups. One-year, death-censored graft survival and patient survival rates ranged from 97.5% to 100% and 96.6% to 100%, respectively. Delayed graft function was uncommon across all BMI groups, ranging from 5.3% to 9.1%, with the lowest incidence in patients with a BMI ≥ 35 kg/m2. Biopsy-proven acute rejection rates at 1 year were similar across all groups (10.1%-14%) as were estimated glomerular filtration rates were at 1, 3, and 5 years. Conclusion: Our results do not show an effect of BMI on posttransplant outcomes, suggesting that relaxation of BMI criteria may be warranted for recipient selection.

Most transplant centers decline morbidly obese people for living kidney donation. Their inclusion in the living donor pool after weight loss and reversal of comorbidities by bariatric surgery could reverse the downward living donation trend. We investigated whether bariatric surgery in the morbidly obese altered their candidacy for donation, complicated their subsequent donor nephrectomy, and impacted their early postoperative outcomes in a series of 22 donors who had bariatric surgery 0.7-22 years prior to laparoscopic living donor nephrectomy. Eighteen would have been excluded from donation prior to bariatric surgery based on a body mass index (BMI) > 40. Seventeen reached a BMI < 35 after bariatric surgery. One had hypertension that resolved after bariatric surgery. Prior bariatric surgery did not influence port placement and laterality of donor nephrectomy. None required open conversion or blood transfusion. In an exploratory comparison with 37 donors with a BMI 35-40, length of stay and warm ischemic time were shorter, blood loss and postoperative complications were similar, and operative time was longer. We therefore advocate the consideration of bariatric surgery in preparation for donation in morbidly obese people since it positively alters their candidacy without major impact on the subsequent living donor nephrectomy and early outcomes.

Hepatitis C (HCV) disease transmission from the use of HCV antibody-positive and HCV nucleic acid test-negative (HCV Ab+/NAT-) kidneys have been anecdotally reported to be absent. We prospectively analyzed kidney transplant (KT) outcomes from HCV Ab+/NAT- donors to HCV naive recipients under T-cell depleting early steroid withdrawal immunosuppression. Allografts from 40 HCV Ab+/NAT- donors were transplanted to 52 HCV Ab- recipients between July 2016 and February 2018. Thirty-three (82.5%) of donors met Public Health Service (PHS) increased risk criteria. De novo HCV infection was detected at 3 months post-KT in one recipient (1.9%). This was a case of transmission from a HCV Ab+ NAT+ donor with an initial false-negative NAT completed using sample collected on donor hospital admission (day 2). At the time of HCV diagnosis, a stored donor sample collected during procurement (day 4) was tested and resulted NAT-positive. Subsequently, sustained virologic response (SVR) was achieved with 12 weeks of glecaprevir/pibrentasvir. One death with functioning graft at 261 days post-KT was determined not related to HCV or donor factors. This experience provides evidence of a low transmission rate of HCV from HCV Ab+/ NAT- kidney donors, thereby arguing for increasing utilization.

The use of donation after circulatory death (DCD) liver allografts has been constrained by limitations in the duration of donor warm ischemia time (DWIT), donor agonal time (DAT), and cold ischemia time (CIT). The purpose of this study is to assess the impact of longer DWIT, DAT, and CIT on graft survival and other outcomes in DCD liver transplants. The Scientific Registry of Transplant Recipients was queried for adult liver transplants from DCD donors between 2009 and 2015. Donor, recipient, and center variables were included in the analysis. During the study period, 2107 patients underwent liver transplant with DCD allografts. In most patients, DWIT and DAT were30 minutes. DWIT was30 minutes in 1804 donors, between 30 and 40 minutes in 248, and40 minutes in 37. There was no difference in graft survival, duration of posttransplant hospital length of stay, and readmission rate between DCD liver transplants from donors with DWIT30 minutes and DWIT between 30 and 40 minutes. Similar outcomes were noted for DAT. In the multivariate analysis, DAT and DWIT were not associated with graft loss. The predictors associated with graft loss were donor age, donor sharing, CIT, recipient admission to the intensive care unit, recipient ventilator dependence, Model for End-Stage Liver Disease score, and low-volume transplant centers. Any CIT cutoff4 hours was associated with increased risk for graft loss. Longer CIT was also associated with a longer posttransplant hospital stay, higher rate of primary nonfunction, and hyperbilirubinemia. In conclusion, slightly longer DAT and DWIT (up to 40 minutes) were not associated with graft loss, longer posttransplant hospitalization, or hospital readmissions, whereas longer CIT was associated with worse outcomes after DCD liver transplants.

Background Given the shortage of available liver grafts, transplantation (LTx) of hepatitis C virus antibody-positive, nucleic acid test-negative (HCV Ab+/NAT-) livers into nonviremic HCV recipients can expand the donor pool. Having previously described the sentinel experience of HCV Ab+/NAT- allografts in nonviremic recipients, we report the growth and extended follow-up of this program for 55 patients compared with recipients of Public Health Services (PHS) increased-risk donor HCV Ab-/NAT- allografts. Study Design A prospective review of all HCV nonviremic LTx patients receiving HCV Ab+/NAT- organs between March 2016 and August 2018 was performed. All HCV Ab+/NAT- organ recipients underwent HCV testing at 3 months and 1-year post-LTx to determine HCV transmission. Results Fifty-five HCV nonviremic candidates received HCV Ab+/NAT- organs; 64% male, median age 59 years (range 36 to 69 years) and median Model for End-Stage Liver Disease score of 22.5. Two recipients were excluded due to death before HCV testing. The HCV disease transmission occurred in 5 recipients (9%). Of these, 4 (80%) underwent anti-HCV treatment with eradication of virus. No patient found to be negative at 3 months seroconverted at 1-year follow-up. No patients who received PHS increased-risk donor HCV Ab-/NAT- organs had viremia develop (0 of 57) and there was no difference in graft and renal function, complications, or survival between HCV Ab+/NAT- recipients and PHS increased-risk donor HCV Ab-/NAT- recipients. Conclusions We report the largest experience with LTx from HCV Ab+/NAT- donors into 55 seronegative recipients with a HCV transmission rate of 9% with no late conversions at 1 year and no difference in function or graft loss compared with PHS increased-risk donor HCV Ab-/NAT- recipients. Due to availability of safe and effective HCV therapies, the use of such organs should be strongly considered to increase the donor organ pool.

INTRODUCTION The use of liver allografts from elderly donors (≥70 years) has increased because of organ shortage and increased life expectancy. The aim of this study is to evaluate the current utilization of elderly donors in United States, recipient selection, and their posttransplant outcomes. METHODS A linkage between Scientific Registry of Transplant Recipients and University HealthSystem Consortium databases was performed. Between January 2007 and December 2011, 12,445 liver transplant (LT) recipients were identified and divided into 2 cohorts based on donor age: 70 years or older (n = 540) and younger than 60 years (n = 10,473). RESULTS Elderly donors accounted for 4.3% of all donors used in the 5-year period. When compared to younger donors, elderly donors were more likely to be women, shared regionally or nationally, and used at higher volume centers. Elderly donor allografts were less likely to be used in recipients with model of end-stage liver disease score higher than 27 (13.2% vs. 23.0%, P < 0.001), hospitalized (16.8% vs. 21.7%, P = 0.03), or on hemodialysis at time of transplant (2.6% vs. 8.2%, P < 0.001). Both recipient groups had similar perioperative mortality, 30-day readmission rates, and short-term patient survival. In the multivariate analysis, including recipient, donor, center and regional factors, donor age 70 years or older was associated with slightly increased risk of graft loss (hazard ratio, 1.3; 95% confidence interval, 1.08-1.56; P = 0.005). CONCLUSIONS The current trend toward the use of elderly donors in liver transplant recipients with low model of end-stage liver disease scores (

Background Classification of acute rejection (AR) based on etiology and timing may provide a means for enhancing therapeutic results and allograft survival. This study evaluated graft and patient survival after the first AR episodes among kidney transplant recipients with an early or late antibody-mediated rejection (AMR), acute cellular rejection (ACR) or mixed AR (MAR). Methods A prospective institutional review board-approved database was queried to identify biopsy-proven first AR episodes occurring from January 2005 to October 2012. The ACR was defined by Banff criteria; borderline AR was excluded. The AMR was defined as 3 of 4 criteria: renal dysfunction, donor specific antibody, C4d positivity on biopsy, and histological changes. The MAR met criteria for both ACR and AMR. Early AR occurred within six months post-transplant. AR episodes were then assigned to 1 of the 6 categories--early AMR, early ACR, early MAR, late AMR, late ACR, and late MAR. Results One hundred eighty-two kidney transplant recipients identified with a first AR episode. Mean follow-up was 773 days (± 715 days). No difference was observed in patient survival. Death-censored graft survival was 84%. Death-censored graft loss was higher with late versus early AMR (P = 0.01) and late versus early ACR (P = 0.03), but not late versus early MAR (P = 0.3). Conclusions The AR type demonstrated a hierarchy for graft survival with ACR better than MAR better than AMR, which persisted for both early and late AR. Improvement in long-term results of AR may require development of specific treatment for individual AR types.

Morbid obesity is a barrier to kidney transplantation due to inferior outcomes, including higher rates of new-onset diabetes after transplantation (NODAT), delayed graft function (DGF), and graft failure. Laparoscopic sleeve gastrectomy (LSG) increases transplant eligibility by reducing BMI in kidney transplant candidates, but the effect of surgical weight loss on posttransplantation outcomes is unknown. Reviewing single-center medical records, we identified all patients who underwent LSG before kidney transplantation from 2011-2016 (n = 20). Post-LSG kidney recipients were compared with similar-BMI recipients who did not undergo LSG, using 2:1 direct matching for patient factors. McNemar's test and signed-rank test were used to compare groups. Among post-LSG patients, mean BMI ± standard deviation (SD) was 41.5 ± 4.4 kg/m2 at initial encounter, which decreased to 32.3 ± 2.9 kg/m2 prior to transplantation (P

The acceptance criteria used for living kidney donors are largely theoretical, as they are not clearly linked to outcomes. The goal of this study was to use implantation biopsies as a surrogate outcome marker to evaluate our living kidney donor selection criteria.One thousand six hundred sequential living kidney donor biopsies were performed between 2001 and 2011. Implantation biopsies were assessed by dedicated renal pathologists according to the Banff criteria. Biopsies with any chronic score of 2 or higher were deemed to have moderate to severe changes (MSC).MSC was present in 4% (n=65) of implantation biopsies and occurred across a wide range of age and other demographics. By multivariate analysis, donor age (odds ratio [95% confidence interval], 1.060 [1.035-1.086]; P0.0001) and donor systolic blood pressure (SBP) (odds ratio [95% confidence interval], 1.022 [1.006-1.037]; P=0.0060) were associated with MSC. Donor gender, body mass index, diastolic blood pressure, glomerular filtration rate, and urinary microalbuminuria were not. MSC was further increased in donors older than 60 years with SBP140 (30% [7 of 23]) and donors older than 60 years with SBP140 and glomerular filtration rate above the 25th percentile (42.8% [3 of 7]). In donors younger than 60 years, combining factors did not show an increased prevalence of MSC. At follow-up, renal function was similar in donors with and without MSC.MSC occurred sporadically in donors with varied characteristics. Although we did not detect patterns to support specific changes in our acceptance criteria, certain subgroups of donors might benefit from close follow-up.

While previous studies have demonstrated short-term efficacy of laparoscopic sleeve gastrectomy in candidates awaiting renal transplantation, the combination of morbid obesity and end-stage renal disease presents unique challenges to perioperative care. We demonstrate how increasing experience and the development of postoperative care guidelines can improve outcomes in this high-risk population.Single-center medical records were reviewed for renal transplantation candidates undergoing laparoscopic sleeve gastrectomy between 2011 and 2015 by a single surgeon. Postoperative care protocols were established and continually refined throughout the study period, including a multidisciplinary approach to inpatient management and hospital discharge planning. The first 100 laparoscopic sleeve gastrectomy patients were included and divided into 4 equal cohorts based on case sequence.Compared with the first 25 patients undergoing laparoscopic sleeve gastrectomy, the last 25 patients had shorter operative times (97.8 ± 27.9 min vs 124.2 ± 33.6 min), lower estimated blood loss (6.6 ± 20.8 mL vs 34.0 ± 38.1 mL), and shorter hospital duration of stay (1.7 ± 2.1 days vs 2.9 ± 0.7 days) (P .01 each). Readmission rates, complications, and 1-year mortality did not differ significantly.Increasing experience and the development of clinical care guidelines in this high-risk population is associated with reduced health care resource utilization and improved perioperative outcomes.

Sensitized renal transplant recipients with high levels of donor-specific alloantibody (DSA) commonly develop antibody-mediated rejection (AMR), which may cause acute graft loss or shorten allograft survival. We examined the efficacy of terminal complement inhibition with the humanized anti-C5 antibody, eculizumab, in the prevention AMR in renal transplant recipients with a positive crossmatch against their living donor. The incidence of biopsy-proven AMR in the first 3 months posttransplant in 26 highly sensitized recipients of living donor renal transplants who received eculizumab posttransplant was compared to a historical control group of 51 sensitized patients treated with a similar plasma exchange (PE)-based protocol without eculizumab. The incidence of AMR was 7.7% (2/26) in the eculizumab group compared to 41.2% (21/51) in the control group (p = 0.0031). Eculizumab also decreased AMR in patients who developed high levels of DSA early after transplantation that caused proximal complement activation. With eculizumab, AMR episodes were easily treated with PE reducing the need for splenectomy. On 1-year protocol biopsy, transplant glomerulopathy was found to be present in 6.7% (1/15) eculizumab-treated recipients and in 35.7% (15/42) of control patients (p = 0.044). Inhibition of terminal complement activation with eculizumab decreases the incidence of early AMR in sensitized renal transplant recipients (ClincalTrials.gov number NCT006707).

BACKGROUND Donor specific alloantibody producing plasma cells (DSA-PCs) appear resistant to conventional immunosuppressive agents. This study aimed to determine the impact of pretransplant monotherapy with the proteasome inhibitor bortezomib on DSA-PCs in sensitized renal allograft candidates and to assess if DSA-PC depletion would enhance the efficacy of DSA removal using plasma exchange (PE). METHODS Only patients with DSA levels considered too high to successfully undergo transplantation with PE alone were included in this study: i.e. those with a baseline B flow cytometric crossmatch (BFXM) >450 against a potential living donor.Four sensitized patients received 4 doses (1.3 mg/m/dose) of bortezomib and 4 received 16 doses. The number of DSA-PCs was determined pre and post-treatment using an ELISPOT assay. Five of these patients underwent post-treatment PE and their response was compared to 8 highly-sensitized patients (BFXM >450) who underwent PE alone. RESULTS When considering all 8 patients as one group, bortezomib treatment decreased DSA-PCs in the marrow (mean±SD=16.7±14.5 DSA-PCs/ml pre-treatment vs. 6.2±3.6 DSA-PCs/ml after treatment, P=0.048). In the time frame of the study, bortezomib alone did not decrease serum DSA levels. However, five bortezomib treated patients underwent PE and showed a greater decease in DSA compared to the historical control group of 8 sensitized patients who underwent PE alone (mean decrease in BFXM channel shift=272.6±92.1 with bortezomib vs 95.4±72.2 in PE alone P=0.008). CONCLUSIONS Bortezomib depletes DSA-PCs and appears to potentiate DSA removal by PE in sensitized renal transplant recipients.

Reflective of the gross national shortage of organs available for transplantation, utilization of extended criteria donor livers has gained momentum, arguing the merits of transplantation with higher risk organs outweighs the risks associated with staying on the waiting list. As a result, high-risk extended criteria allografts, previously referred to as marginal or compromised organs, have become an important part of the donor organ supply. Unfortunately, the use of “expanded” criteria liver allografts remains undefined. Therefore, due to regional heterogeneity in the landscape of national scarcity, allocation policies for extended criteria allografts have largely been transplant center specific and calibrated based on predicted recipient benefit, projected reduction in waitlist mortality, and parity. The utility, selection, and performance of “extended criteria” donor allograft livers are examined in this review.

Background Severe obesity has been shown to limit access to renal transplantation in patients with end stage renal disease (ESRD). Laparoscopic sleeve gastrectomy (LSG) has been performed in the ESRD population to assist in achieving waitlist and transplant eligibility. Little is known about how LSG impacts the bioequivalence tacrolimus products and immunosuppression pharmacokinetics. Methods This was a prospective, open-label, single-dose, crossover, two-period pharmacokinetic (PK) study. The purpose of this study was to assess single-dose PK of immediate-release tacrolimus (IR-TAC), extended-release tacrolimus (ER-TAC), and mycophenolic acid (MPA) in adult ESRD patients post-LSG. Results Twenty-three subjects were included in the 24-hour PK assessments. The ratio of geometric means between ER-TAC and IR-TAC was 103.5% (90% CI 89.6 – 119.6%) for AUC0-24 and 92.5% (90% CI 80.4 – 106.4%) for Cmax. PK parameters were similar between ER-TAC and IR-TAC, except for Cmin (p=0.004) and Cmax (p=0.04). MPA AUC0-24 was similar when given with either ER-TAC or IR-TAC (p=0.32). Patients expressing CYP3A5*1 genotypes had lower tacrolimus AUC0-24 values versus those with CYP3A5*3/*3 (IR-TAC p

Summary The aim of this study was to analyze the impact of morbid obesity in recipients on peritransplant resource utilization and survival outcomes. Using a linkage between the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases, we identified 12 445 patients who underwent liver transplantation (LT) between 2007 and 2011 and divided them into two cohorts based on recipient body mass index (BMI

In Ohio, the obesity rate has increased from 21.5% in 2000 to 30.1% in 2012. Nonalcoholic steatohepatitis is believed to be increasing as an indication for orthotopic liver transplantation.We evaluated the diagnosis of nonalcoholic steatohepatitis as an indication for orthotopic liver transplantation and ensuing outcomes relative to other common hepatic diseases requiring orthotopic liver transplantation in Ohio. We queried 2,356 patients with nonalcoholic steatohepatitis, alcoholic cirrhosis (ETOH), and hepatitis C cirrhosis from the Ohio Solid Organ Transplantation Consortium who were listed for and/or received an orthotopic liver transplant from 2000 to 2012.The proportion of listed patients with nonalcoholic steatohepatitis increased from 0% to 26% and the proportion of transplanted patients increased from 0% to 23.4%. Compared with patients with hepatitis C and ETOH, patients with nonalcoholic steatohepatitis were older, and more likely to be white, and have private insurance (P .05 for each). There was no difference in median waiting time among patients with nonalcoholic steatohepatitis, hepatitis C, and ETOH (P = .18) and Model for End-Stage Liver Disease scores at orthotopic liver transplantation among patients with nonalcoholic steatohepatitis, hepatitis C (P = .48), and ETOH (P = .27). Patient and graft survival after orthotopic liver transplantation was comparable between patients with nonalcoholic steatohepatitis and ETOH (P = .79 and P = .86, respectively); however, patients with nonalcoholic steatohepatitis had better patient and graft survival compared with patients with hepatitis C after orthotopic liver transplantation (P .01 and P = .02, respectively). Additionally, body mass index had no influence on overall or graft survival for patients with nonalcoholic steatohepatitis undergoing orthotopic liver transplantation.This study reflects the growing potential for transplantation in patients with fatty liver disease and suggests the outcomes are equivalent or superior to other common indications for orthotopic liver transplantation.

The results of simultaneous liver-kidney transplants in highly sensitized recipients have been controversial in terms of antibody-mediated rejection and kidney allograft outcomes. This case report provides a detailed and sophisticated documentation of histocompatibility and pathologic data in a simultaneous liver-kidney transplant performed in a recipient with multiple high-titered class I and II antidonor HLA antibodies and a strongly positive cytotoxic crossmatch. Patient received induction with steroids, rituximab, and eculizumab without lymphocyte depleting agents. The kidney transplant was delayed by 6 hours after the liver transplant to allow more time to the liver allograft to “absorb” donor-specific antibodies (DSA). Interestingly, the liver allograft did not prevent immediate antibody-mediated injury to the kidney allograft in this highly sensitized recipient. Anti-HLA single antigen bead analysis of liver and kidney allograft biopsy eluates revealed deposition of both class I and II DSA in both liver and kidney transplants during the first 2 weeks after transplant. Afterward, both liver and kidney allograft functions improved and remained normal after a year with progressive reduction in serum DSA values.

Morbid obesity is a barrier to renal transplantation and is inadequately addressed by medical therapy. We present results of a prospective evaluation of laparoscopic sleeve gastrectomy (LSG) for patients failing to achieve significant weight loss with medical therapy. Over a 25-month period, 52 obese renal transplant candidates meeting NIH guidelines for metabolic surgery underwent LSG. Mean age was 50.0 ± 10.0 years with an average preoperative BMI of 43.0 ± 5.4 kg/m(2) (range 35.8-67.7 kg/m(2)). Follow-up after LSG was 220 ± 152 days (range 26-733 days) with last BMI of 36.3 ± 5.3 kg/m(2) (range 29.2-49.8 kg/m(2)) with 29 (55.8%) patients achieving goal BMI of