Transplantation Direct最新文献

Background: A prior single-center, retrospective cohort study identified baseline lung allograft dysfunction (BLAD) as a risk factor for death in bilateral lung transplant recipients. In this multicenter prospective cohort study, we test the association of BLAD with death in bilateral lung transplant recipients, identify clinical risk factors for BLAD, and assess its association with allograft injury on the molecular level.

Methods: This multicenter, prospective cohort study included 173 bilateral lung transplant recipients that underwent serial pulmonary function testing and plasma collection for donor-derived cell-free DNA at prespecified time points. BLAD was defined as failure to achieve ≥80% predicted for both forced expiratory volume in 1 s and forced vital capacity after lung transplant, on 2 consecutive measurements at least 3 mo apart.

Results: BLAD was associated with increased risk of death (hazard ratio, 1.97; 95% confidence interval [CI], 1.05-3.69; P = 0.03) but not chronic lung allograft dysfunction alone (hazard ratio, 1.60; 95% CI, 0.87-2.95; P = 0.13). Recipient obesity (odds ratio, 1.69; 95% CI, 1.15-2.80; P = 0.04) and donor age (odds ratio, 1.03; 95% CI, 1.02-1.05; P = 0.004) increased the risk of developing BLAD. Patients with BLAD did not demonstrate higher log₁₀(donor-derived cell-free DNA) levels compared with no BLAD (slope [SE]: -0.0095 [0.0007] versus -0.0109 [0.0007]; P = 0.15).

Conclusions: BLAD is associated with an increased risk of death following lung transplantation, representing an important posttransplant outcome with valuable prognostic significance; however, early allograft specific injury on the molecular level does not increase the risk of BLAD, supporting further mechanistic insight into disease pathophysiology.

Background: The cause of liver disease is changing, but its impact on liver transplantation (LT) for hepatocellular carcinoma (HCC) in women and men is unclear. We performed a nationwide study to assess the prevalence and posttransplant survival outcomes of the various causes of liver disease in women and men with HCC.

Methods: Data were obtained from the United Network for Organ Sharing database from 2000 to 2022. Data related to the listing, transplant, waitlist mortality, and posttransplant mortality for HCC were extracted. The proportion of HCC related to the various causes of liver disease among LT candidates and recipients and posttransplant survival were compared between women and men.

Results: A total of 51 721 individuals (39 465 men, 12 256 women) with HCC were included. From 2000 to 2022, nonalcoholic steatohepatitis (NASH) was the fastest-growing cause of liver disease among female LT candidates with HCC (P < 0.01), followed by alcohol-associated liver disease. NASH overtook chronic hepatitis C as the leading cause of liver disease in 2020 and 2022 among waitlisted women and men with HCC, respectively. Female patients with HCC spent a significantly longer time on the LT waitlist compared with male patients (β: 8.73; 95% confidence interval [CI], 2.91-14.54). Female patients with HCC from alcohol-associated liver disease also have a lower probability of receiving LT (subdistribution hazard ratio: 0.90; 95% CI, 0.82-0.99). Among transplant recipients with NASH HCC, female sex was associated with lower posttransplant mortality compared with male sex (hazard ratio: 0.79; 95% CI, 0.70-0.89; P < 0.01).

Conclusions: Women have a significantly longer waitlist duration compared with men. NASH is now the leading cause of liver disease among both female and male LT candidates and recipients with HCC.

Background: Systemic barriers to posttransplant care, including access to immunosuppressant medications, contribute to higher rates of kidney transplant failure in racial minorities. Matching donor and recipient HLA alleles reduce allorecognition, easing reliance on immunosuppression. We hypothesize that 0-antigen mismatch transplants may provide stronger protection against graft loss in racial minorities.

Methods: We compared adult, single-organ, deceased-donor kidney transplants in the United States from 2007 to 2016 by degree of HLA mismatch (0- versus ≥1-antigen mismatch). We examined time-to-allograft failure, with death as a competing event, using multivariable Weibull models, stratified by recipient race (White versus non-White), and evaluated the interaction between mismatch and recipient race. We used Kaplan-Meier imputation to account for competing risk of death.

Results: We analyzed 102 114 transplants (median follow-up, 5.6 y; 16 862 graft losses, 18 994 deaths). Zero-antigen mismatch was associated with improved allograft survival (adjusted subdistribution hazard ratio [sHR] 0.80; 95% confidence interval [CI], 0.75-0.85). When stratified by recipient race, the effect of 0-antigen mismatch was more pronounced in White (unadjusted sHR 0.78; 95% CI, 0.72-0.83) versus non-White recipients (sHR 0.88; 95% CI, 0.79-0.99; interaction P = 0.04). The differential effect was attenuated after adjusting for covariates (sHR 0.78; 95% CI, 0.73-0.84 versus sHR 0.87; 95% CI, 0.77-0.98; interaction P = 0.10).

Conclusions: Zero-antigen mismatch transplants conferred a 20% risk reduction in allograft loss, which was similar between non-White and White recipients. This may reflect an increased degree of mismatch at other HLA alleles and non-HLA alleles in non-White recipients or because of the extent of systemic barriers to healthcare borne by minority recipients.

Background: Uncontrolled donation after circulatory death (uDCD) increases organ availability for kidney transplantation (KT) at the expense of a higher risk of primary graft nonfunction (PNF). At least half of the cases of PNF are secondary to graft venous thrombosis. The potential benefit from prophylactic anticoagulation in this scenario remains unclear.

Methods: In this single-center retrospective study we compared 2 consecutive cohorts of KT from uDCD with increased (≥0.8) renal resistive index (RRI) in the Doppler ultrasound examination performed within the first 24-72 h after transplantation: 36 patients did not receive anticoagulation ("nonanticoagulation group") and 71 patients underwent prophylactic anticoagulation until normalization of RRI in follow-up Doppler examinations ("anticoagulation group").

Results: Anticoagulation was initiated at a median of 2 d (interquartile range, 2-3) after transplantation and maintained for a median of 12 d (interquartile range, 7-18). In 4 patients (5.6%), anticoagulation had to be prematurely stopped because of the development of a hemorrhagic complication. In comparison with the nonanticoagulation group, recipients in the anticoagulation group had a lower 2-wk cumulative incidence of graft venous thrombosis (19.4% versus 0.0%; P < 0.001) and PNF (19.4% versus 2.8%; P = 0.006). The competing risk analysis with nonthrombotic causes of PNF as the competitive event confirmed the higher risk of graft thrombosis in the nonanticoagulation group (P = 0.0001). The anticoagulation group had a higher incidence of macroscopic hematuria (21.1% versus 5.6%; P = 0.049) and blood transfusion requirements (39.4% versus 19.4%; P = 0.050) compared with the nonanticoagulation group. No graft losses or deaths were attributable to complications potentially associated with anticoagulation.

Conclusions: Early initiation of prophylactic anticoagulation in selected KT recipients from uDCD with an early Doppler ultrasound RRI of ≥0.8 within the first 24-72 h may reduce the incidence of graft venous thrombosis as a cause of PNF.

Background: There is no consensus on the ideal strategy to treat posttransplant focal segmental glomerulosclerosis. The multiple-target therapy, which consisted of high-dose intravenous cyclosporine, prednisone, and plasmapheresis, showed favorable results.

Methods: This single-center, prospective study sought to evaluate the multiple-target therapy in an independent cohort of patients.

Results: Thirteen patients with posttransplant focal segmental glomerulosclerosis received multiple-target therapy. Complete remission was achieved in 2 patients (15.4%), and partial remission in another 2 patients (15.4%). Four patients (30.7%) did not show remission, and 5 patients (38%) lost the graft because of posttransplant focal segmental glomerulosclerosis during the 12-mo follow-up. Premature discontinuation of treatment occurred in 10 patients (77%), all associated with infectious adverse events. Cytomegalovirus was the most common complication, and preemptive therapy was used instead of prophylaxis.

Conclusions: In this cohort of patients, the efficacy of the multiple-target therapy was poor and limited by the high incidence of infectious adverse events.

Background: Variation in donation after circulatory death (DCD) organ recovery and liver transplant practices exist among transplant centers. This study aimed to evaluate these practices among centers in the United States.

Methods: Scientific Registry of Transplant Recipients data were accessed to identify centers that performed liver transplantation in 2021 and 2022. Surveys were sent to transplant centers that consistently performed ≥5 DCD liver transplants per year.

Results: DCD liver transplants were performed by 95 centers (65.1%) of the 146 liver transplant centers in the United States. Survey results were recorded from 42 centers that consistently performed ≥5 DCD liver transplants per year, with a 59.5% response rate. Withdrawal-to-asystole and agonal time were used to define donor warm ischemia time (WIT) in 16% and 84% centers, respectively. Fifty-six percent of the centers did not use oxygen saturation to define donor WIT. Systolic blood pressure cutoffs used to define agonal time varied between 50 and 80 mm Hg, donor age cutoffs ranged between 55 and 75 y, and cold ischemia times varied between 4 and 10 h. Seventy-six percent of centers used normothermic machine perfusion for DCD liver transplantation.

Conclusions: This study highlights the wide variation in use, recovery, and definition of donor WIT. Using national data to rigorously define best practices will encourage greater utilization of this important donor resource.

Background: The HIV Organ Policy Equity Act legalizes organ procurement from donors with HIV (HIV D+). A prior survey of Organ Procurement Organizations (OPOs) estimated >2000 HIV D+ referrals/year; however, only 30-35 HIV D+/year have had organs procured. Given this gap, we sought to understand HIV D+ referrals and procurements in practice.

Methods: We prospectively collected data on all OPO-reported HIV D+ referrals, including reasons for nonprocurement. We evaluated trends and compared HIV D+ characteristics by procurement status using regression, chi-squared tests, and Wilcoxon rank-sum tests.

Results: From December 23, 2015 to May 31, 2021, there were 710 HIV D+ referrals from 49 OPOs, of which 171 (24%) had organs procured. HIV D+ referrals increased from 7 to 15 per month (P < 0.001), and the procurement rate increased from 10% to 39% (P < 0.001). Compared with HIV D+ without procurement, HIV D+ with procurement were younger (median age 36 versus 50 y), more commonly White (46% versus 36%), and more often had trauma-related deaths (29% versus 8%) (all P < 0.001). Nonprocurement was attributed to medical reasons in 63% of cases, of which 36% were AIDS-defining infections and 64% were HIV-unrelated, commonly due to organ failure (36%), high neurologic function (31%), and cancer (14%). Nonprocurement was attributed to nonmedical reasons in 26% of cases, commonly due to no authorization (42%), no waitlist candidates (21%), or no transplant center interest (20%).

Conclusions: In the early years of the HIV Organ Policy Equity Act, actual HIV D+ referrals were much lower than prior estimates; however, the numbers and procurement rates increased over time. Nonprocurement was attributed to both medical and nonmedical issues, and addressing these issues could increase organ availability.

Background: MELD 3.0 introduces changes to address waitlist disparities for liver transplant (LT) candidates. Ascites and hepatic encephalopathy (HE) are important milestones in the natural history of cirrhosis regardless of the Model for End-Stage Liver Disease (MELD) score. We aim to assess the impact of ascites and HE and its interaction with MELD 3.0 on waitlist mortality.

Methods: This is a retrospective study of patients listed for LT in the Organ Procurement and Transplantation Network database from 2016 to 2021. The primary outcome was waitlist mortality (death/delisting for too sick to LT). Ascites/HE were classified as moderate ascites without moderate HE (mAscites), moderate HE without moderate ascites (mHE), both moderate ascites/HE (mBoth), and neither. MELD 3.0 scores were categorized as <20, 20-29, 30-39, and ≥40.

Results: Of 39 025 candidates, 29% had mAscites, 3% mHE, and 8% mBoth. One-year waitlist mortality was 30%, 38%, and 47%, respectively, compared with 17% (all P < 0.001) for those with neither. In multivariable Cox regression, the adjusted risk of waitlist mortality associated with mAscites (versus neither) was a hazard ratio (HR) of 1.76 (95% confidence interval [CI], 1.55-2.00) when the MELD 3.0 score was <20, significantly higher than when the MELD 3.0 score was 20-29 (HR 1.40; 95% CI, 1.27-1.54), 30-39 (HR 1.19; 95% CI, 1.04-1.35), and ≥40 (HR 1.14; 95% CI, 0.91-1.43, interaction P < 0.05 for all). A similar pattern was observed by MELD 3.0 for both moderate ascites/HE.

Conclusions: The presence of moderate ascites alone, or combined with moderate HE, not only increases the risk of waitlist mortality but also has a differential effect by MELD 3.0, especially at lower MELD scores. Earlier strategies addressing this group and improving treatment plans or access to LT regardless of MELD remain needed.

Background: Kidney transplant centers lack consistent diagnostic malnutrition tools. The Academy of Nutrition and Dietetics and American Society of Parenteral Nutrition Adult Malnutrition Criteria (AMC) is the widely accepted and utilized tool by Registered Dietitian Nutritionists (RDNs) to diagnose malnutrition.

Methods: In this single-center, retrospective observational study, we evaluated the outcomes of prekidney transplant malnutrition based on Academy of Nutrition and Dietetics and American Society of Parenteral Nutrition AMC, as well as the individual components of the AMC, on posttransplant outcomes including length of stay, delayed graft function (DGF), early readmission, cardiovascular events, acute rejection, death-censored graft failure, and death. Bivariable and multivariable logistic regression models were used to assess the association of malnutrition or its components with outcomes of interest.

Results: A total of 367 recipients were included, of whom 36 (10%) were malnourished (23 moderately and 13 severely) at pretransplant evaluation. In adjusted models, pretransplant malnutrition was significantly associated with increased risk for early readmission (adjusted odds ratio 2.86; 95% confidence interval: 1.14-7.21; P = 0.03) and with DGF (adjusted odds ratio 8.33; 95% confidence interval: 1.07-64.6; P = 0.04). Muscle depletion was also associated with an increased risk for readmission and with DGF. Fat depletion and reduced functionality in the adjusted model were only associated with increased risk for readmission.

Conclusions: Malnutrition could be an important consideration for selecting kidney transplant recipients because it was associated with poor clinical outcomes. A multidisciplinary approach with the involvement of RDNs to outline a nutrition intervention plan may help mitigate some of the poor outcomes.