Angiotensin II in liver transplantation (AngLT-1): protocol of a randomised, double-blind, placebo-controlled trial.

INTRODUCTION: Catecholamine vasopressors such as norepinephrine are the standard drugs used to maintain mean arterial pressure during liver transplantation. At high doses, catecholamines may impair organ perfusion. Angiotensin II is a peptide vasoconstrictor that may improve renal perfusion pressure and glomerular filtration rate, a haemodynamic profile that could reduce acute kidney injury. Angiotensin II is approved for vasodilatory shock but has not been rigorously evaluated for treatment of hypotension during liver transplantation. The objective is to assess the efficacy of angiotensin II as a second-line vasopressor infusion during liver transplantation. This trial will establish the efficacy of angiotensin II in decreasing the dose of norepinephrine to maintain adequate blood pressure. Completion of this study will allow design of a follow-up, multicentre trial powered to detect a reduction of organ injury in liver transplantation. METHODS AND ANALYSIS: This is a double-blind, randomised clinical trial. Eligible subjects are adults with a Model for End-Stage Liver Disease Sodium Score ≥25 undergoing deceased donor liver transplantation. Subjects are randomised 1:1 to receive angiotensin II or saline placebo as the second-line vasopressor infusion. The study drug infusion is initiated on reaching a norepinephrine dose of 0.05 µg kg-1 min-1 and titrated per protocol. The primary outcome is the dose of norepinephrine required to maintain a mean arterial pressure ≥65 mm Hg. Secondary outcomes include vasopressin or epinephrine requirement and duration of hypotension. Safety outcomes include incidence of thromboembolism within 48 hours of the end of surgery and severe hypertension. An intention-to-treat analysis will be performed for all randomised subjects receiving the study drug. The total dose of norepinephrine will be compared between the two arms by a one-tailed Mann-Whitney U test. ETHICS AND DISSEMINATION: The trial protocol was approved by the local Institutional Review Board (#20-30948). Results will be posted on ClinicalTrials.gov and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: ClinicalTrials.govNCT04901169.

Normothermic Machine Perfusion of Donor Livers for Transplantation in the United States: A Randomized Controlled Trial.

OBJECTIVE: To compare conventional low-temperature storage of transplant donor livers [static cold storage (SCS)] with storage of the organs at physiological body temperature [normothermic machine perfusion (NMP)]. BACKGROUND: The high success rate of liver transplantation is constrained by the shortage of transplantable organs (eg, waiting list mortality >20% in many centers). NMP maintains the liver in a functioning state to improve preservation quality and enable testing of the organ before transplantation. This is of greatest potential value with organs from brain-dead donor organs (DBD) with risk factors (age and comorbidities), and those from donors declared dead by cardiovascular criteria (donation after circulatory death). METHODS: Three hundred eighty-three donor organs were randomized by 15 US liver transplant centers to undergo NMP (n = 192) or SCS (n = 191). Two hundred sixty-six donor livers proceeded to transplantation (NMP: n = 136; SCS: n = 130). The primary endpoint of the study was "early allograft dysfunction" (EAD), a marker of early posttransplant liver injury and function. RESULTS: The difference in the incidence of EAD did not achieve significance, with 20.6% (NMP) versus 23.7% (SCS). Using exploratory, "as-treated" rather than "intent-to-treat," subgroup analyses, there was a greater effect size in donation after circulatory death donor livers (22.8% NMP vs 44.6% SCS) and in organs in the highest risk quartile by donor risk (19.2% NMP vs 33.3% SCS). The incidence of acute cardiovascular decompensation at organ reperfusion, "postreperfusion syndrome," as a secondary outcome was reduced in the NMP arm (5.9% vs 14.6%). CONCLUSIONS: NMP did not lower EAD, perhaps related to the inclusion of lower-risk liver donors, as higher-risk donor livers seemed to benefit more. The technology is safe in standard organ recovery and seems to have the greatest benefit for marginal donors.

Pulmonary Injury Causing a Massive Air Leak During Liver Transplantation: A Case Report and Discussion of Decision-Making.

Pulmonary injury can occur during liver transplantation in patients with prior liver surgery, infection, or hepatocellular carcinoma treatments. Compromise of gas exchange during liver transplantation mandates rapid, multidisciplinary decision-making. We present a case of lung parenchymal injury causing a massive air leak during the dissection phase of a liver transplant. An endobronchial blocker was used for emergency lung isolation. Since oxygenation and pH were stable, we proceeded with liver transplantation to minimize graft ischemic time, followed by thoracic repair. The postoperative course was notable for adequate early liver function and discharge after prolonged postoperative ventilation and tube thoracostomy drainage.

Real-world implementation of normothermic machine perfusion: A detailed analysis of intraoperative and early postoperative impact.

BACKGROUND: Outcome data for the great majority of liver normothermic machine perfusion (NMP) cases derive from the strict confines of clinical trials. Detailed specifics regarding the intraoperative and early postoperative impact of NMP on reperfusion injury and its sequelae during real-world use of this emerging technology remain largely unavailable. METHODS: We analyzed transplants performed in a 3-month pilot period during which surgeons invoked commercial NMP at their discretion. Living donor, multi-organ, and hypothermic machine perfusion transplants were excluded. RESULTS: Intraoperatively, NMP (n = 24) compared to static cold storage (n = 25) recipients required less peri-reperfusion bolus epinephrine (0 vs. 60 µg; p < .001) and post-reperfusion fresh frozen plasma (2.5 vs. 7.0 units; p = .0069), platelets (.0 vs. 2.0 units; p = .042), and hemostatic agents (0% vs. 24%; p = .010). Time from incision to venous reperfusion did not differ (3.6 vs. 3.1; p = .095) but time from venous reperfusion to surgery end was shorter for NMP recipients (2.3 vs. 2.8 h; p = .0045). Postoperatively, NMP recipients required fewer red blood cell (1.0 vs. 4.0 units; p = .0083) and fresh frozen plasma (4.0 vs. 7.0 units; p = .046) transfusions, had shorter intensive care unit stays (33.5 vs. 58.4 h; p = .012), and experienced less early allograft dysfunction according to both the Model for Early Allograft Function Score (3.4 vs. 5.0; p = .0047) and peak AST within 10 days of transplant (619 vs. 1,181 U/L; p = .036). Liver acceptance for the corresponding recipient was conditional on NMP use for 63% (15/24) of cases. CONCLUSION: Real-world NMP use was associated with significantly lower intensity of reperfusion injury and intraoperative and postoperative care that may translate into patient benefit.

A Multi-Modal Approach to Islet and Pancreas Transplantation With Calcineurin-Sparing Immunosuppression Maintains Long-Term Insulin Independence in Patients With Type I Diabetes.

Long-term success in beta-cell replacement remains limited by the toxic effects of calcineurin inhibitors (CNI) on beta-cells and renal function. We report a multi-modal approach including islet and pancreas-after-islet (PAI) transplant utilizing calcineurin-sparing immunosuppression. Ten consecutive non-uremic patients with Type 1 diabetes underwent islet transplant with immunosuppression based on belatacept (BELA; n = 5) or efalizumab (EFA; n = 5). Following islet failure, patients were considered for repeat islet infusion and/or PAI transplant. 70% of patients (four EFA, three BELA) maintained insulin independence at 10 years post-islet transplant, including four patients receiving a single islet infusion and three patients undergoing PAI transplant. 60% remain insulin independent at mean follow-up of 13.3 ± 1.1 years, including one patient 9 years after discontinuing all immunosuppression for adverse events, suggesting operational tolerance. All patients who underwent repeat islet transplant experienced graft failure. Overall, patients demonstrated preserved renal function, with a mild decrease in GFR from 76.5 ± 23.1 mL/min to 50.2 ± 27.1 mL/min (p = 0.192). Patients undergoing PAI showed the greatest degree of renal impairment following initiation of CNI (56% ± 18.7% decrease in GFR). In our series, repeat islet transplant is ineffective at maintaining long-term insulin independence. PAI results in durable insulin independence but is associated with impaired renal function secondary to CNI dependence.

Steroid Avoidance After Adult Living Donor Liver Transplant: A Cohort Analysis.

Although steroid avoidance (SA) has been studied in deceased donor liver transplant, little is known about SA in living donor liver transplant (LDLT). We report the characteristics and outcomes, including the incidence of early acute rejection (AR) and complications of steroid use, in 2 cohorts of LDLT recipients. Methods: Routine steroid maintenance (SM) after LDLT was stopped in December 2017. Our single-center retrospective cohort study spans 2 eras. Two hundred forty-two adult recipients underwent LDLT with SM (January 2000-December 2017), and 83 adult recipients (December 2017-August 2021) underwent LDLT with SA. Early AR was defined as a biopsy showing pathologic characteristics within 6 mo after LDLT. Univariate and multivariate logistic regressions were performed to evaluate the effects of relevant recipient and donor characteristics on the incidence of early AR in our cohort. Results: Neither the difference in early AR rate between cohorts (SA 19/83 [22.9%] versus SM 41/242 [17%]; P = 0.46) nor a subset analysis of patients with autoimmune disease (SA 5/17 [29.4%] versus SM 19/58 [22.4%]; P = 0.71) reached statistical significance. Univariate and multivariate logistic regressions for early AR identified recipient age to be a statistically significant risk factor (P < 0.001). Of the patients without diabetes before LDLT, 3 of 56 (5.4%) on SA versus 26 of 200 (13%) on SM needed medications prescribed for glucose control at the time of discharge (P = 0.11). Patient survival was similar between SA and SM cohorts (SA 94% versus SM 91%, P = 0.34) 3 y after transplant. Conclusions: LDLT recipients treated with SA do not exhibit significantly higher rates of rejection or increased mortality than patients treated with SM. Notably, this result is similar for recipients with autoimmune disease.

Advances and innovations in living donor liver transplant techniques, matching and surgical training: Meeting report from the living donor liver transplant consensus conference.

The practice of LDLT currently delivers limited impact in western transplant centers. The American Society of Transplantation organized a virtual consensus conference in October 2021 to identify barriers and gaps to LDLT growth, and to provide evidence-based recommendations to foster safe expansion of LDLT in the United States. This article reports the findings and recommendations regarding innovations and advances in approaches to donor-recipient matching challenges, the technical aspects of the donor and recipient operations, and surgical training. Among these themes, the barriers deemed most influential/detrimental to LDLT expansion in the United States included: (1) prohibitive issues related to donor age, graft size, insufficient donor remnant, and ABO incompatibility; (2) lack of acknowledgment and awareness of the excellent outcomes and benefits of LDLT; (3) ambiguous messaging regarding LDLT to patients and hospital leadership; and (4) a limited number of proficient LDLT surgeons across the United States. Donor-recipient mismatching may be circumvented by way of liver paired exchange. The creation of a national registry to generate granular data on donor-recipient matching will guide the practice of liver paired exchange. The surgical challenges to LDLT are addressed herein and focuses on the development of robust training pathways resulting in proficiency in donor and recipient surgery. Utilizing strong mentorship/collaboration programs with novel training practices under the auspices of established training and certification bodies will add to the breadth and depth of training.

Number of Local Regional Therapies for Hepatocellular Carcinoma and Peri-Operative Outcomes after Liver Transplantation.

The wait times for patients with hepatocellular carcinoma (HCC) listed for liver transplant are longer than ever, which has led to an increased reliance on the use of pre-operative LRTs. The impact that multiple rounds of LRTs have on peri-operative outcomes following transplant is unknown. This was a retrospective single center analysis of 298 consecutive patients with HCC who underwent liver transplant (January 2017 to May 2021). The data was obtained from two institution-specific databases and the TransQIP database. Of the 298 patients, 27 (9.1%) underwent no LRTs, 156 (52.4%) underwent 1-2 LRTs, and 115 (38.6%) underwent ≥3 LRTs prior to LT. The patients with ≥3 LRTs had a significantly higher rate of bile leak compared to patients who received 1-2 LRTs (7.0 vs. 1.3%, p = 0.014). Unadjusted and adjusted regression analyses demonstrated a significant association between the total number of LRTs administered and bile leak, but not rates of overall biliary complications. The total number of LRTs was not significantly associated with any other peri-operative or post-operative outcome measure. These findings support the aggressive use of LRTs to control HCC in patients awaiting liver transplant, with further evaluation needed to confirm the biliary leak findings.

Change in Body Mass Index and Attributable Risk of New-Onset Hypertension Among Obese Living Kidney Donors.

OBJECTIVE: To examine whether body mass index (BMI) changes modify the association between kidney donation and incident hypertension. BACKGROUND: Obesity increases hypertension risk in both general and living kidney donor (LKD) populations. Donation-attributable risk in the context of obesity, and whether weight change modifies that risk, is unknown. METHODS: Nested case-control study among 1558 adult LKDs (1976-2020) with obesity (median follow-up: 3.6 years; interquartile range: 2.0-9.4) and 3783 adults with obesity in the Coronary Artery Risk Development in Young Adults (CARDIA) and Atherosclerosis Risk in Communities (ARIC) studies (9.2 y; interquartile range: 5.3-15.8). Hypertension incidence was compared by donor status using conditional logistic regression, with BMI change investigated for effect modification. RESULTS: Overall, LKDs and nondonors had similar hypertension incidence [incidence rate ratio (IRR): 1.16, 95% confidence interval (95% CI): 0.94-1.43, P =0.16], even after adjusting for BMI change (IRR: 1.25, 95% CI: 0.99-1.58, P =0.05). Although LKDs and nondonors who lost >5% BMI had comparable hypertension incidence (IRR: 0.78, 95% CI: 0.46-1.34, P =0.36), there was a significant interaction between donor and >5% BMI gain (multiplicative interaction IRR: 1.62, 95% CI: 1.15-2.29, P =0.006; relative excess risk due to interaction: 0.90, 95% CI: 0.24-1.56, P =0.007), such that LKDs who gained weight had higher hypertension incidence than similar nondonors (IRR: 1.83, 95% CI: 1.32-2.53, P <0.001). CONCLUSIONS: Overall, LKDs and nondonors with obesity had similar hypertension incidence. Weight stability and loss were associated with similar hypertension incidence by donor status. However, LKDs who gained >5% saw increased hypertension incidence versus similar nondonors, providing support for counseling potential LKDs with obesity on weight management postdonation.

Diabetes-free survival among living kidney donors and non-donors with obesity: A longitudinal cohort study.

BACKGROUND: Approval of living kidney donors (LKD) with end-stage kidney disease (ESKD) risk factors, such as obesity, has increased. While lifetime ESKD development data are lacking, the study of intermediate outcomes such as diabetes is critical for LKD safety. Donation-attributable diabetes risk among persons with obesity remains unknown. The purpose of this study was to evaluate 10-year diabetes-free survival among LKDs and non-donors with obesity. METHODS: This longitudinal cohort study identified adult, LKDs (1976-2020) from 42 US transplant centers and non-donors from the Coronary Artery Risk Development in Young Adults (1985-1986) and the Atherosclerosis Risk in Communities (1987-1989) studies with body mass index ≥30 kg/m2. LKDs were matched to non-donors on baseline characteristics (age, sex, race, body mass index, systolic and diastolic blood pressure) plus diabetes-specific risk factors (family history of diabetes, impaired fasting glucose, smoking history). Accelerated failure time models were utilized to evaluate 10-year diabetes-free survival. FINDINGS: Among 3464 participants, 1119 (32%) were LKDs and 2345 (68%) were non-donors. After matching on baseline characteristics plus diabetes-specific risk factors, 4% (7/165) LKDs and 9% (15/165) non-donors developed diabetes (median follow-up time 8.5 (IQR: 5.6-10.0) and 9.1 (IQR: 5.9-10.0) years, respectively). While not significant, LKDs were estimated to live diabetes-free 2 times longer than non-donors (estimate 1.91; 95% CI: 0.79-4.64, p = 0.15). CONCLUSIONS: LKDs with obesity trended toward living longer diabetes-free than non-donors with obesity, suggesting within the decade following donation there was no increased diabetes risk among LKDs. Further work is needed to evaluate donation-attributable diabetes risk long-term.

Nodular Regenerative Hyperplasia After Liver Transplant; It's All in the Presentation.

There is a paucity of data on nodular regenerative hyperplasia after liver transplant. We aim to define the clinical disease trajectory and identify predictors of outcome for this rare diagnosis. This is a retrospective review of postulated risk factors and outcome in patients with nodular regenerative hyperplasia. Patients were classified as having a late presentation if nodular regenerative hyperplasia was diagnosed > 48 months from transplant, and symptomatic if portal hypertensive symptoms were present. Forty-nine of 3,711 (1.3%) adult recipients developed nodular regenerative hyperplasia, and mortality was 32.7% with an average follow up of 84.6 months. The MELD-Na 6 months after diagnosis did not change significantly. Patients with symptomatic portal hypertension at the time of diagnosis had a significantly higher risk of mortality (51.8%) compared to patients with liver test abnormalities alone (10.5%). 44.9% of patients had no previously postulated risk factor. Anastomotic vascular complications do not appear to be the etiology in most patients. The results suggest the vast majority of patients presenting with liver test abnormalities alone have stable disease and excellent long term survival, in contrast to the 56.3% mortality seen in patients that present more than 48 months after LT with symptomatic portal hypertension at diagnosis.

Therapeutic Living Donor Nephrectomy for Proximal Ureteral Pathology: A Longitudinal Case Series.

OBJECTIVE: To raise awareness that patients with proximal ureteral stricture who elect for nephrectomy can consider donating the kidney. We present a series of patients undergoing therapeutic living donor nephrectomy (TLDN), a scenario in which a patient undergoing nephrectomy for an underlying medical problem donates the kidney to a person with end-stage renal disease. This practice is underutilized, and only a single TLDN with proximal ureteral stricture has been previously described. We aim to help define the indications, risks, and benefits for patients. METHODS: This is a retrospective case series of seven therapeutic donors with proximal ureteral pathology and stone disease. Patient characteristics, donor work up, operative details, and donor and recipient outcome were collected. RESULTS: All seven donors had proximal ureteral pathology, and six of the seven had nephrolithiasis or ureterolithiasis. After electing for nephrectomy, the mean time to TLDN was 57.9 days. No recipients experienced delayed graft function . Mean follow up was 40.1 months (range 8-131), and the most recent follow-up mean creatinine was 1.08 (mg/dL). Graft and recipient survival is 100%. No recipients developed recurrence of ureteral stricture or stones. CONCLUSION: This is the first series demonstrating patients with proximal ureteral stricture, even with concomitant stone disease, may donate kidneys for transplantation. Recipient outcomes suggest this practice is safe, and appropriately selected patients that have already elected for nephrectomy should receive counseling about this opportunity. Importantly, patients who donate a kidney receive waiting list priority if they ever need a kidney transplant in the future.

Which recipient pretransplant factors, such as MELD, renal function, sarcopenia, and recent sepsis influence suitability for and outcome after living donor liver transplantation? A systematic review of the literature and expert panel recommendations.

BACKGROUND: Varied access to deceased donors across the globe has resulted in differential living donor liver transplant (LDLT) practices and lack of consensus over the influence of models for end stage liver disease (MELD), renal function, sarcopenia, or recent infection on short-term outcomes. OBJECTIVES: Consider these risk factors in relation to patient selection and provide recommendations. DATA SOURCES: Ovid MEDLINE, Embase, Scopus, Google Scholar, Cochrane Central. METHODS: PRIMSA systematic review and GRADE. PROSPERO ID: RD42021260809 RESULTS: MELD >25-30 alone is not a contraindication to LDLT, and multiple studies found no increase in short term mortality in high MELD patients. Contributing factors such as muscle mass, acute physiologic assessment and chronic health evaluation score, donor age, graft weight/recipient weight ratio, and inclusion of the middle hepatic vein in a right lobe graft influence morbidity and mortality in high MELD patients. Higher mortality is observed with pretransplant renal dysfunction, but short-term mortality is rare. Sarcopenia and recent infection are not contraindications to LDLT. Morbidity and prolonged LOS are common, and more frequent in patients with renal dysfunction, nutritional deficiency or recent infection. CONCLUSIONS: When individual risk factors are studied mortality is low and graft loss is infrequent, but morbidity is common. MELD, especially with concomitant risk factors, had the greatest influence on short term outcome, and recent infection had the least. A multidisciplinary team of experts should carefully assess patients with multiple risk factors, and an optimal graft is recommended.

Kidney transplant candidacy evaluation and waitlisting practices in the United States and their association with access to transplantation.

There are limited data on the degree of variability in practices surrounding prioritization of referrals for transplant evaluation and criteria for transplant candidacy and their association with transplantation rates. We surveyed transplant programs across the United States between January 2020 and May 2020 to determine current pre-transplantation practices. We examined the relation between these reported practices and the outcomes of waitlisted patients at responding programs between January 2015 and March 2021 using Scientific Registry of Transplant Recipients data. We used adjusted Cox models with random effects to accommodate clustering by program. Primary outcomes included living or deceased donor transplantation. Of 172 surveyed programs, 90 participated. Substantial variations were noted in when the candidacy evaluation began (13% reported when eGFR was <30 mL/min/1.73 m2 and 17% reported no set policy) and the approach to pre-transplantation cardiac workup (multi-modality [58%], stress echocardiogram [20%]). Using adjusted models, a program policy of using other measures of body habitus to determine transplant candidacy rather than requiring patients to meet a body mass index (BMI) threshold of ≤35 kg/m2 (reference group) for candidacy was associated with a higher hazard of living donor transplantation (HR 1.83 [95% CI 1.10-3.03]). Pre-transplant practices vary substantially across the United States, and select practices were associated with transplantation rates.

Impact of Portable Normothermic Blood-Based Machine Perfusion on Outcomes of Liver Transplant: The OCS Liver PROTECT Randomized Clinical Trial.

IMPORTANCE: Ischemic cold storage (ICS) of livers for transplant is associated with serious posttransplant complications and underuse of liver allografts. OBJECTIVE: To determine whether portable normothermic machine perfusion preservation of livers obtained from deceased donors using the Organ Care System (OCS) Liver ameliorates early allograft dysfunction (EAD) and ischemic biliary complications (IBCs). DESIGN, SETTING, AND PARTICIPANTS: This multicenter randomized clinical trial (International Randomized Trial to Evaluate the Effectiveness of the Portable Organ Care System Liver for Preserving and Assessing Donor Livers for Transplantation) was conducted between November 2016 and October 2019 at 20 US liver transplant programs. The trial compared outcomes for 300 recipients of livers preserved using either OCS (n = 153) or ICS (n = 147). Participants were actively listed for liver transplant on the United Network of Organ Sharing national waiting list. INTERVENTIONS: Transplants were performed for recipients randomly assigned to receive donor livers preserved by either conventional ICS or the OCS Liver initiated at the donor hospital. MAIN OUTCOMES AND MEASURES: The primary effectiveness end point was incidence of EAD. Secondary end points included OCS Liver ex vivo assessment capability of donor allografts, extent of reperfusion syndrome, incidence of IBC at 6 and 12 months, and overall recipient survival after transplant. The primary safety end point was the number of liver graft-related severe adverse events within 30 days after transplant. RESULTS: Of 293 patients in the per-protocol population, the primary analysis population for effectiveness, 151 were in the OCS Liver group (mean [SD] age, 57.1 [10.3] years; 102 [67%] men), and 142 were in the ICS group (mean SD age, 58.6 [10.0] years; 100 [68%] men). The primary effectiveness end point was met by a significant decrease in EAD (27 of 150 [18%] vs 44 of 141 [31%]; P = .01). The OCS Liver preserved livers had significant reduction in histopathologic evidence of ischemia-reperfusion injury after reperfusion (eg, less moderate to severe lobular inflammation: 9 of 150 [6%] for OCS Liver vs 18 of 141 [13%] for ICS; P = .004). The OCS Liver resulted in significantly higher use of livers from donors after cardiac death (28 of 55 [51%] for the OCS Liver vs 13 of 51 [26%] for ICS; P = .007). The OCS Liver was also associated with significant reduction in incidence of IBC 6 months (1.3% vs 8.5%; P = .02) and 12 months (2.6% vs 9.9%; P = .02) after transplant. CONCLUSIONS AND RELEVANCE: This multicenter randomized clinical trial provides the first indication, to our knowledge, that normothermic machine perfusion preservation of deceased donor livers reduces both posttransplant EAD and IBC. Use of the OCS Liver also resulted in increased use of livers from donors after cardiac death. Together these findings indicate that OCS Liver preservation is associated with superior posttransplant outcomes and increased donor liver use. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02522871.

Motivations and outcomes of compatible living donor-recipient pairs in paired exchange.

Increasing numbers of compatible pairs are choosing to enter paired exchange programs, but motivations, outcomes, and system-level effects of participation are not well described. Using a linkage of the Scientific Registry of Transplant Recipients and National Kidney Registry, we compared outcomes of traditional (originally incompatible) recipients to originally compatible recipients using the Kaplan-Meier method. We identified 154 compatible pairs. Most pairs sought to improve HLA matching. Compared to the original donor, actual donors were younger (39 vs. 50 years, p < .001), less often female (52% vs. 68%, p < .01), higher BMI (27 vs. 25 kg/m², p = .03), less frequently blood type O (36% vs. 80%, p < .001), and had higher eGFR (99 vs. 94 ml/min/1.73 m², p = .02), with a better LKDPI (median 7 vs. 22, p < .001). We observed no differences in graft failure or mortality. Compatible pairs made 280 additional transplants possible, many in highly sensitized recipients with long wait times. Compatible pair recipients derived several benefits from paired exchange, including better donor quality. Living donor pairs should receive counseling regarding all options available, including kidney paired donation. As more compatible pairs choose to enter exchange programs, consideration should be given to optimizing compatible pair and hard-to-transplant recipient outcomes.

Bariatric surgery prior to transplantation and risk of early hospital re-admission, graft failure, or death following kidney transplantation.

Bariatric surgery has been shown to be safe in the dialysis population. Whether bariatric surgery before kidney transplantation influences posttransplant outcomes has not been examined nationally. We included severely obese (BMI >35) dialysis patients between 18 and 70 years who received a kidney transplant according to the US Renal Data System. We determined the association between history of bariatric surgery and risk of 30-day readmission, graft failure, or death after transplantation using multivariable logistic, Fine-Gray, and Cox models. We included 12 573 patients, of whom 503 (4%) received bariatric surgery before transplantation. Median age at transplant was 53 years; 42% were women. Overall, history of bariatric surgery was not statistically significantly associated with graft failure (HR 1.02; 95% CI 0.77-1.35) or death (HR 1.10; 95% CI 0.84-1.45). However, sleeve gastrectomy (vs. no bariatric surgery) was associated with lower risk of graft failure (HR 0.39; 95% CI 0.16-0.95). In conclusion, history of bariatric surgery prior to kidney transplantation was not associated with allograft or patient survival, but findings varied by surgery type. Sleeve gastrectomy was associated with better graft survival and should be considered in severely obese transplant candidates receiving dialysis.

A case report: anaphylaxis to cefazolin during renal transplant surgery.

BACKGROUND: While there exist case reports of anaphylaxis occurring during renal transplant surgery, descriptions of continuing transplant surgery post-anaphylaxis have been scarce. Anaphylactic reactions that present solely with hypotension without pulmonary or mucocutaneous signs have yet to be described during renal transplant surgery. CASE PRESENTATION: Here we report a case of a 33-year-old female with end-stage renal disease who underwent cadaveric renal transplant. She developed anaphylaxis following the administration of cefazolin. Despite this reaction, the surgery was ultimately completed after patient stabilization, and the patient had excellent graft function postoperatively. The patient had an elevated tryptase at the time of the reaction and postoperative allergy testing revealed a positive intradermal test to cefazolin. Written informed consent was obtained from the patient for all procedures, studies, and publication of this case report. CONCLUSIONS: This is the first case of a successful zero-mismatch cadaveric renal transplant following an anaphylactic reaction to cefazolin. Although anaphylaxis during transplant surgery typically warrants cancellation due to the hemodynamic effects that may lead to graft dysfunction, here we describe a case where surgery was continued following patient stabilization. The decision to proceed with surgery despite an intraoperative emergency along with the management and workup of intraoperative anaphylaxis are described, which can be beneficial for others who are presented with similar scenarios in the future.

Retransplantation After Living Donor Liver Transplantation: Data from the Adult to Adult Living Donor Liver Transplantation Study.

BACKGROUND: The use of living donor liver transplantation (LDLT) for primary liver transplantation (LT) may quell concerns about allocating deceased donor organs if the need for retransplantation (re-LT) arises because the primary LT did not draw from the limited organ pool. However, outcomes of re-LT after LDLT are poorly studied. The purpose of this study was to analyze the Adult to Adult Living Donor Liver Transplantation Study (A2ALL) data to report outcomes of re-LT after LDLT, with a focus on long-term survival after re-LT. METHODS: A retrospective review of A2ALL data collected between 1998 and 2014 was performed. Patients were excluded if they received a deceased donor LT. Demographic data, postoperative outcomes and complications, graft and patient survival, and predictors of re-LT and patient survival were assessed. RESULTS: Of the 1065 patients who underwent LDLT during the study time period, 110 recipients (10.3%) required re-LT. In multivariable analyses, hepatitis C virus, longer length of stay at LDLT, hepatic artery thrombosis, biliary stricture, infection, and disease recurrence were associated with an increased risk of re-LT. Patient survival among re-LT patients was significantly inferior to those who underwent primary transplant only at 1 (86% versus 92%), 5 (64% versus 82%), and 10 years (44% versus 68%). CONCLUSIONS: Approximately 10% of A2ALL patients who underwent primary LDLT required re-LT. Compared with patients who underwent primary LT, survival among re-LT recipients was worse at 1, 5, and 10 years after LT, and re-LT was associated with a significantly increased risk of death in multivariable modeling (hazard ratios, 2.29; P < 0.001).

Understanding the Final Disposition of Livers Declined After the Start of Procurement: A Nationwide Organ Procurement Organization Effort.

Declining a liver offer during organ procurement likely increases the risk of discard, but the specifics around late reallocation remain obscure. This voluntarily submitted, prospectively collected data describe late declines and the ultimate disposition of 893 livers. Once a liver suffered an intraoperative decline, only 49% of recovered livers were transplanted. Livers declined ≥80 minutes prior to cross-clamp were transplanted 80% of the time versus livers declined ≥80 minutes after cross-clamp, which were transplanted 45% of the time. The final disposition of these livers was into a predetermined backup patient (51%) or required an out-of-sequence expedited allocation (42%). Prerecovery imaging and prerecovery biopsy did not influence the ability to reallocate a liver, and livers from donors after circulatory death are rarely successfully reallocated. In conclusion, this study begins to shed light on this seemingly common practice. A total of 85% of centers had an intraoperative decline, but 4% of centers accounted for 25% of the declines. Organ procurement organizations often enter expedited liver allocation, and instituting a cross-clamp delay to allow for reallocation may influence the disposition of these liver grafts. Expedited allocation was more time consuming than allocation into a predetermined backup. Although a certain number of intraoperative declines probably suggests a healthy amount of donor selection aggressiveness at the time of the initial organ offer, the 47% risk of discard of livers declined intraoperatively suggests that United Network for Organ Sharing should consider systematically collecting data about intraoperative declines so we can learn more about this event that influences organ utilization.