Showing papers in "Clinical Transplantation in 2021"

SARS-COV-2 vaccination with BNT162B2 in renal transplant patients: Risk factors for impaired response and immunological implications.

Abstract: Solid organ transplant patients are at a higher risk for poor CoronaVirus Disease-2019 (COVID-19)-related outcomes and have been included as a priority group in the vaccination strategy worldwide. We assessed the safety and efficacy of a two-dose vaccination cycle with mRNA-based COVID-19 vaccine (BNT162b2) among 82 kidney transplant outpatients followed in our center in Rome, Italy. After a median of 43 post-vaccine days, a SARS-CoV-2 anti-Spike seroprevalence of 52.4% (n = 43/82) was observed. No impact of the vaccination on antibody-mediated rejection or graft function was observed, and no significant safety concerns were reported. Moreover, no de novo HLA-donor-specific antibodies (DSA) were detected during the follow-up period. Only one patient with pre-vaccination HLA-DSA did not experience an increased intensity of the existing HLA-DSA. During the follow-up, only one infection (mild COVID-19) was observed in a patient after receiving the first vaccine dose. According to the multivariable logistic regression analysis, lack of seroconversion after two-dose vaccination independently associated with patient age ≥60 years (OR = 4.50; P = .02) and use of anti-metabolite as an immunosuppressant drug (OR = 5.26; P = .004). Among younger patients not taking anti-metabolites, the seroconversion rate was high (92.9%). Further larger studies are needed to assess the best COVID-19 vaccination strategy in transplanted patients.

Outcomes of COVID-19 in hospitalized solid organ transplant recipients compared to a matched cohort of non-transplant patients at a national healthcare system in the United States.

Abstract: Data describing outcomes of solid organ transplant (SOT) recipients with coronavirus disease 2019 (COVID-19) are variable, and the association between SOT status and mortality remains unclear. In this study, we compare clinical outcomes of SOT recipients hospitalized with COVID-19 between March 10, and September 1, 2020, to a matched cohort of non-SOT recipients at a national healthcare system in the United States (US). From a population of 43 461 hospitalized COVID-19-positive patients, we created a coarsened exact matched cohort of 4035 patients including 128 SOT recipients and 3907 weighted matched non-SOT controls. Multiple logistic regression was used to evaluate association between SOT status and clinical outcomes. Among the 4035 patients, median age was 60 years, 61.7% were male, 21.9% were Black/African American, and 50.8% identified as Hispanic/Latino ethnicity. Patients with a history of SOT were more likely to die within the study period when compared to matched non-SOT recipients (21.9% and 14.9%, respectively; odds ratio [OR] 1.93; 95% confidence interval [CI]: 1.18-3.15). Moreover, SOT status was associated with increased odds of receiving invasive mechanical ventilation (OR [95% CI]: 2.34 [1.51-3.65]), developing acute kidney injury (OR [95% CI]: 2.41 [1.59-3.65]), and receiving vasopressor support during hospitalization (OR [95% CI]: 2.14 [1.31-3.48]).

Pig kidney xenotransplantation: Progress toward clinical trials

Abstract: Pig organ xenotransplantation offers a solution to the shortage of deceased human organs for transplantation. The pathobiological response to a pig xenograft is complex, involving antibody, complement, coagulation, inflammatory, and cellular responses. To overcome these barriers, genetic manipulation of the organ-source pigs has largely been directed to two major aims-(a) deletion of expression of the known carbohydrate xenoantigens against which humans have natural (preformed) antibodies, and (b) transgenic expression of human protective proteins, for example, complement- and coagulation-regulatory proteins. Conventional (FDA-approved) immunosuppressive therapy is unsuccessful in preventing an adaptive immune response to pig cells, but blockade of the CD40:CD154 costimulation pathway is successful. Survival of genetically engineered pig kidneys in immunosuppressed nonhuman primates can now be measured in months. Non-immunological aspects, for example, pig renal function, a hypovolemia syndrome, and rapid growth of the pig kidney after transplantation, are briefly discussed. We suggest that patients on the wait-list for a deceased human kidney graft who are unlikely to receive one due to long waiting times are those for whom kidney xenotransplantation might first be considered. The potential risk of infection, public attitudes to xenotransplantation, and ethical, regulatory, and financial aspects are briefly addressed.

Kidney transplant recipients vaccinated before transplantation maintain superior humoral response to SARS-CoV-2 vaccine.

Abstract: Majority of transplant recipients did not develop an appreciable humoral response following SARS-CoV-2 vaccine, in contrast to dialysis patients and healthy individuals. We analyzed the serologic response to BNT162b2 (Pfizer-BioNTech) vaccine in a cohort of 19 kidney transplant recipients, vaccinated prior to transplantation, compare to 109 recipients vaccinated after transplantation, and to 39 healthcare workers, by determining the level of anti-spike antibodies after transplantation. All controls and 17 of 19 (90%) of recipients vaccinated before transplant were seropositive, while only 49 of 109 (45%) recipients vaccinated post-transplant had positive serology (P < .001). Median anti-spike IgG in the group of kidney transplant recipients vaccinated after transplantation (10.7 AU/ml, [IQR 0-62.5]) was lower than the patients vaccinated before transplantation (66.2 AU/ml [21.6-138]), which was significantly lower than in the controls (156 AU/ml [99.7-215.5]). Negative humoral response was associated with vaccination post transplantation (odds ratio 22.4), older age (OR = 1.04), and longer time on dialysis (OR = 1.02), while higher lymphocyte count at time of vaccination was protective (OR = .52). Our findings of sustained superior humoral response to SARS-CoV-2 vaccine in kidney transplant recipients vaccinated prior to transplantation strongly support the recommendations of SARS-CoV-2 vaccination of transplant candidates, especially those younger than 60 years.

Excess mortality in solid organ transplant recipients hospitalized with COVID-19: A large-scale comparison of SOT recipients hospitalized with or without COVID-19.

Abstract: Background Solid-organ transplant (SOT) recipients with COVID-19 have higher risk of adverse outcomes compared to the general population. Whether hospitalized SOT recipients with COVID-19 are at higher risk of mortality than SOT recipients hospitalized for other causes, including non-COVID-19 pneumonia, remains unclear. Methods We used logistic regression to compare outcomes of SOT recipients hospitalized with COVID-19 to non-COVID-19 related admissions and with non-COVID-19 pneumonia. Results Of 17,012 hospitalized SOT recipients, 1,682 had COVID-19. Those with COVID-19 had higher odds of ICU admission (adjusted odds ratio [aOR] 2.12 [95%CI: 1.88-2.39]) and mechanical ventilation (aOR 3.75 [95%CI: 3.24-4.33]). COVID-19 was associated with higher odds of in-hospital death, which was more pronounced earlier in the pandemic (aOR 9.74 [95%CI: 7.08-13.39] for April/May versus aOR 7.08 [95%CI: 5.62-8.93] for June through November 2020; p-interaction = 0.03). Compared to SOT recipients hospitalized with non-COVID-19 pneumonia, odds of in-hospital death were higher in SOT recipients with COVID-19 (aOR 2.44 [95% CI: 1.90-3.13]), regardless of time of hospitalization (p-interaction >0.40). Conclusions In this large cohort of SOT recipients, hospitalization with COVID-19 was associated with higher odds of complications and in-hospital mortality than non-COVID-19 related admissions, and 2.5-fold higher odds of in-hospital mortality, compared to SOT recipients with non-COVID-19 pneumonia. This article is protected by copyright. All rights reserved.

Incidence, risk factors, treatment, and consequences of antibody-mediated kidney transplant rejection: A systematic review.

Abstract: Background Antibody-mediated rejection (AMR) is a leading cause of kidney allograft failure, but its incidence, risk factors, and outcomes are not well understood. Methods We searched Ovid MEDLINE, Cochrane, EMBASE, and Scopus from January 2000-January 2020 to identify published cohorts of ≥ 500 incident adult or 75 pediatric kidney transplant recipients followed for ≥ 1 year posttransplant. Results At least two reviewers screened 5061 articles and abstracts; 28 met inclusion criteria. Incidence of acute AMR was 1.1%-21.5%; most studies reported 3%-12% incidence, usually within the first year posttransplant. Few studies reported chronic AMR incidence, from 7.5%-20.1% up to 10 years. Almost all patients with acute or chronic AMR received corticosteroids and intravenous immunoglobulin; most received plasmapheresis, and approximately half with rituximab. Most studies examining death-censored graft failure identified AMR as an independent risk factor. Few reported refractory AMR rates or outcomes, and none examined costs. Most studies were single-center and varied greatly in design. Conclusions Cohort studies of kidney transplant recipients demonstrate that AMR is common and associated with increased risk of death-censored graft failure, but studies vary widely regarding populations, definitions, and reported incidence. Gaps remain in our understanding of refractory AMR, its costs, and resulting quality of life.

Influence of patient characteristics and immunosuppressant management on mortality in kidney transplant recipients hospitalized with coronavirus disease 2019 (COVID-19).

Abstract: The influence of patient characteristics and immunosuppression management on COVID-19 outcomes in kidney transplant recipients (KTRs) remains uncertain. We performed a single-center, retrospective review of all adult KTRs admitted to the hospital with confirmed COVID-19 between 03/15/2020 and 05/15/2020. Patients were followed from the date of admission up to 1 month following hospital discharge or study conclusion (06/15/2020). Baseline characteristics, laboratory parameters, and immunosuppression were compared between survivors and patients who died to identify predictors of mortality. 38 KTRs with a mean baseline eGFR of 52.5 ml/min/1.73 m2 were hospitalized during the review period. Maintenance immunosuppression included tacrolimus (84.2%), mycophenolate (89.5%), and corticosteroids (81.6%) in the majority of patients. Eleven patients (28.9%) died during the hospitalization. Older age (OR = 2.05; 1.04-4.04), peak D-dimer (OR = 1.20; 1.04-1.39), and peak white blood cell count (OR = 1.11; 1.02-1.21) were all associated with mortality among KTRs hospitalized for COVID-19. Increased mortality was also observed among KTRs with concomitant HIV infection (87.5% vs. 36.1%; p < .01). Conversely, immunosuppression intensity and degree of reduction following COVID-19 diagnosis were not associated with either survival or acute allograft rejection. Our findings potentially support a strategy of individualization of immunosuppression targets based on patient-specific risk factors, rather than universal immunosuppression reduction for KTRs at risk from COVID-19.

State-of-the-art machine learning algorithms for the prediction of outcomes after contemporary heart transplantation: Results from the UNOS database.

Abstract: Purpose We sought to develop and validate machine learning (ML) models to increase the predictive accuracy of mortality after heart transplantation (HT). Methods and results We included adult HT recipients from the United Network for Organ Sharing (UNOS) database between 2010 and 2018 using solely pre-transplant variables. The study cohort comprised 18 625 patients (53 ± 13 years, 73% males) and was randomly split into a derivation and a validation cohort with a 3:1 ratio. At 1-year after HT, there were 2334 (12.5%) deaths. Out of a total of 134 pre-transplant variables, 39 were selected as highly predictive of 1-year mortality via feature selection algorithm and were used to train five ML models. AUC for the prediction of 1-year survival was .689, .642, .649, .637, .526 for the Adaboost, Logistic Regression, Decision Tree, Support Vector Machine, and K-nearest neighbor models, respectively, whereas the Index for Mortality Prediction after Cardiac Transplantation (IMPACT) score had an AUC of .569. Local interpretable model-agnostic explanations (LIME) analysis was used in the best performing model to identify the relative impact of key predictors. ML models for 3- and 5-year survival as well as acute rejection were also developed in a secondary analysis and yielded AUCs of .629, .609, and .610 using 27, 31, and 91 selected variables respectively. Conclusion Machine learning models showed good predictive accuracy of outcomes after heart transplantation.

Impact of heart transplant allocation change on competing waitlist outcomes among listing strategies.

Abstract: In 2018, the United Network for Organ Sharing (UNOS) adopted a 6-tier system for heart allocation which shifted patterns in listing strategies. The effects of the change on waitlist survival and transplantation rates have yet to be substantiated by analysis of competing outcomes among various listing strategies. This study included all adult patients listed for first-time heart transplantation in UNOS between 10/17/15 and 6/12/20. Clinical characteristics were compared before and after allocation change among various listing strategies: no support, inotropes, intra-aortic balloon pump, durable left ventricular assist device (LVAD), temporary VAD, and extracorporeal membrane oxygenation. Fine-Gray proportional subhazard models were used to estimate the effect of allocation change on competing waitlist outcomes-transplantation, death, or removal from waitlist-among each strategy. During the study period, there were 17 422 patients listed for heart transplantation. Among each listing strategy, clinical characteristics were similar before and after allocation change. Subhazard models demonstrated reduced risk for waitlist mortality (p < .001) among each strategy except temporary VAD and increased transplantation rates (p < .001) among each strategy except for durable LVAD. These results validate the association of the new allocation system on waitlist outcomes across listing strategies.

eHealth literacy and web-based patient portal usage among kidney and liver transplant recipients.

Abstract: Patient portals promote self-management, but require skills with electronic health information which can be measured by a patient's eHealth literacy. We aimed to describe eHealth literacy among a population of kidney transplant (KT) and liver transplant (LT) recipients and to investigate the relationship between eHealth literacy and Web-based patient portal utilization. We conducted phone surveys (August 2016-March 2017) among 178 KT and 110 LT recipients at two large transplant centers, including the eHealth Literacy Scale (eHEALS) and items assessing routine portal usage. Portal users were defined as routine if usage was every day, weekly, or monthly. The mean eHEALS score was 30.9 (SD: 5.4), and 45.4% routinely used the patient portal more than a few times per month. Routine users had higher eHealth literacy than non-routine users and non-users (31.97 vs. 29.97 vs. 28.20, p < .001). Routine users had higher eHealth literacy scores compared with non-users after adjusting for transplant organ type, age, educational level, employment status, mobile Internet access, and transplant center (OR: 1.10, 95% CI: 1.03-1.17). KT and LT recipients who routinely use patient portals have high eHealth literacy compared with other diseased populations, which should be leveraged by encouraging routine usage to improve post-transplant health and medication adherence.

Renal transplantation during the SARS-CoV-2 pandemic in the UK: Experience from a large-volume center.

Abstract: There is uncertainty about the safety of kidney transplantation during the SARS-CoV-2 pandemic due to the risk of donor transmission, nosocomial infection and immunosuppression use. We describe organ donation and transplant practice in the UK and assess whether kidney transplantation conferred a substantial risk of harm. Data from the UK transplant registry were used to describe kidney donation and transplant activity in the UK, and a detailed analysis of short-term, single-center, patient results in two periods: during the pre-pandemic era from 30th December 2019 to 8th March 2020 ("Pre-COVID era") and the 9th March 2020 to 19th May 2020 ("COVID era"). Donor and recipient numbers fell by more than half in the COVID compared to the pre-COVID era in the UK, but there were more kidney transplants performed in our center (42 vs. 29 COVID vs. pre-COVID respectively). Overall outcomes, including re-operation, delayed graft function, primary non-function, acute rejection, length of stay and graft survival were similar between COVID and pre-COVID era. 6/71 patients became infected with SARS-CoV-2 but all were discharged without critical care requirement. Transplant outcomes have remained similar within the COVID period and no serious sequelae of SARS-CoV-2 infection were observed in the peri-transplant period.

Enhanced recovery after surgery programs improve short-term outcomes after liver transplantation-A systematic review and meta-analysis.

Abstract: This systematic review aimed to investigate the available quality of evidence (QOE) of enhanced recovery after surgery (ERAS) for liver transplantation (LT) on short-term outcomes, grade recommendations, and identify relevant components for ERAS protocols. A systematic review and meta-analysis were conducted on short-term outcomes after LT when applying comprehensive ERAS protocols (> 1 ERAS component) versus control groups (CRD42021210374), following the GRADE approach for grading QOE and strength of recommendations. Endpoints were morbidity, mortality, length of stay, and readmission rates after ERAS for LT. Of 858 screened articles, two randomized controlled trials, two prospective, and one retrospective cohort studies were included (2002-2020). Frequent ERAS components were early extubation and postoperative antibiotic, fluid, and nutrition management. Overall complications were reduced in ERAS versus control cohorts (OR .4 (CI .2, .7), with no significant differences in mortality and hospital readmission rates. Intensive care unit and hospital length of stay were shorter in ERAS groups (percentage decrease, 55% and 29%, respectively). QOE for individual outcomes was rated moderate to low. ERAS protocols in LT are related to improved short-term outcomes after LT (QOE; Moderate to low | Grade of Recommendation; Strong), but currently lack standardization.

Using race to estimate glomerular filtration and its impact in kidney transplantation.

Abstract: Since direct measurement of glomerular filtration rate (GFR) is time-consuming and more expensive, estimated GFR (eGFR) based on measured laboratory values is widely used to determine kidney function. Commonly used formulae to calculate eGFR are dependent on variables, which include filtration markers like serum creatinine and patient characteristics including race. Medical algorithms which utilize race are increasingly being scrutinized, as race is recognized to be a social construct rather than a biologic one. eGFR calculations have important implications for kidney transplantation, both in the listing of candidates as well as in the evaluation of potential kidney donors. This review considers the specific implications of race-based eGFR calculations on recipient evaluation and on decisions related to living kidney donation. We suggest a potential policy solution to ensure that racial and ethnic minority patients are not disadvantaged by eGFR as a result of current calculation methods.

The impact of the SARS-CoV-2 pandemic and COVID-19 on lung transplantation in the UK: Lessons learned from the first wave.

Abstract: Background Lung transplantation is particularly susceptible to the impact of the Severe Acute Respiratory Syndrome Coronavirus-type 2 (SARS-CoV-2) pandemic, and evaluation of changes to practice is required to inform future decision making. Methods A retrospective review of the UK Transplant Registry (UKTR) and national survey of UK lung transplant centres has been performed. Results There was geographic variation in the prevalence of COVID-19 infection across the UK. The number of donors fell by 48% during the early pandemic period. Lung utilisation fell to 10% (compared to 24% for the same period of 2019). The number of lung transplants performed fell by 77% from 53, March to May 2019, to 12. Seven (58%) of these were performed in a single centre, designated 'COVID-light'. The number of patients who died on the lung transplant waiting list increased, compared to the same period of 2019 (p=0.0118). Twenty-six lung transplant recipients with confirmed COVID-19 infection were reported during the study period. Conclusion As the pandemic continues, reviewing practice and implementing the lessons learned during this period, including the use of robust donor testing strategies and the provision of 'COVID-light' hospitals, is vital in ensuring the safe continuation of our lung transplant programme.

Impact of the United Network for organ sharing 2018 donor heart allocation system on transplant morbidity and mortality.

Abstract: BACKGROUND While the revised UNOS HTx donor allocation system aimed to minimize waitlist mortality by prioritizing more critically ill transplant candidates, there is concern for increased post-transplant morbidity and mortality. We examined the impact of the revised allocation system on waitlist and post-transplant outcomes at a high-volume transplant center. METHODS One hundred and sixty nine adult patients underwent first-time single-organ HTx one year before (Era 1:79 patients) and after (Era 2:90 patients) implementation of the new allocation system (10/18/2018). Clinical characteristics, waitlist outcomes, and post-transplant morbidity and mortality were compared. RESULTS Era 2 patients were twice as likely to be transplanted on temporary mechanical circulatory support (43% vs. 19%, p < .0001). While Era 2 waitlist time was shorter (10 vs. 43 days, p < .001), exception status requests (21.1% vs. 17.9%) and waitlist mortality (3.3% vs. 2.2%) were similar. There was no difference in primary graft dysfunction, intensive care unit or hospital length of stay, readmissions, rejection, allograft vasculopathy, or 1-year survival (91.1% vs. 93.7%). CONCLUSIONS In a high-volume center, the revised HTx allocation system shortened waitlist time with no significant change in waitlist mortality or observed impact on post-transplant outcomes. With careful patient selection, the revised allocation system may optimize waitlist and post-transplant outcomes.

Donor-derived cell-free DNA is associated with cardiac allograft vasculopathy.

Abstract: BACKGROUND The role of donor-derived cell-free DNA (dd-cfDNA) in screening for cardiac allograft vasculopathy (CAV) is unknown. We hypothesized that dd-cfDNA correlates with CAV, markers of inflammation, and angiogenesis in stable heart transplant (HT) recipients. METHODS Sixty-five HT recipients ≥2 years post-transplant, without recent rejection, were stratified by high (≥0.12%) versus low levels (<0.12%) of dd-cfDNA. A targeted amplification, next-generation sequencing assay (AlloSure® ; CareDx, Inc.) was used to detect dd-cfDNA. Peripheral blood inflammatory and angiogenesis markers were assessed using a multiplex immunoassay system (Bioplex® ). RESULTS Of 65 patients, 58 patients had a known CAV status and were included. Thirty had high levels of dd-cfDNA (≥0.12%), and 28 had low levels (<0.12%). CAV was present in 63% of patients with high dd-cfDNA vs. 35% with low dd-cfDNA (p = .047). Donor-specific antibodies were present in 25% of patients with high dd-cfDNA vs. 3.8% in those with low dd-cfDNA (p = .03). There were no differences in rejection episodes, inflammatory, or angiogenesis markers. Importantly, dd-cfDNA levels were not different when stratified by time post-transplant. CONCLUSIONS Higher dd-cfDNA levels were associated with CAV in stable chronic HT recipients. Further studies are warranted to investigate a possible association between dd-cfDNA levels and CAV severity and whether dd-cfDNA can predict CAV progression.

Pediatric lung transplantation as standard of care

Abstract: For infants, children, and adolescents with progressive advanced lung disease, lung transplantation represents the ultimate therapy option. Fortunately, outcomes after pediatric lung transplantation have improved in recent years now producing good long-term outcomes, no less than comparable to adult lung transplantation. The field of pediatric lung transplantation has rapidly advanced; thus, this review aims to update on important issues such as transplant referral and assessment, and extra-corporal life support as "bridge to transplantation". In view of the ongoing lack of donor organs limiting the success of pediatric lung transplantation, donor acceptability criteria and surgical options of lung allograft size reduction are discussed. Post-transplant, immunosuppression is vital for prevention of allograft rejection; however, evidence-based data on immunosuppression are scarce. Drug-related side effects are frequent, close therapeutic drug monitoring is highly advised with an individually tailored patient approach. Chronic lung allograft dysfunction (CLAD) remains the Achilles' heel of pediatric lung transplant limiting its long-term success. Unfortunately, therapy options for CLAD are still restricted. The last option for progressive CLAD would be consideration for lung re-transplant; however, numbers of pediatric patients undergoing lung re-transplantation are very small and its success depends highly on the optimal selection of the most suitable candidate.

Extracorporeal photopheresis and its role in heart transplant rejection: prophylaxis and treatment

Abstract: Heart transplantation is the gold standard therapeutic option for select patients with end-stage heart failure. Unfortunately, successful long-term outcomes of heart transplantation can be hindered by immune-mediated rejection of the cardiac allograft, specifically acute cellular rejection, antibody-mediated rejection, and cardiac allograft vasculopathy. Extracorporeal photopheresis is a cellular immunotherapy that involves the collection and treatment of white blood cells contained in the buffy coat with a photoactive psoralen compound, 8-methoxy psoralen, and subsequent irradiation with ultraviolet A light. This process is thought to cause DNA and RNA crosslinking, ultimately leading to cell destruction. The true mechanism of therapeutic action remains unknown. In the last three decades, extracorporeal photopheresis has shown promising results and is indicated for a variety of conditions. The American Society for Apheresis currently recommends the use of extracorporeal photopheresis for the treatment of cutaneous T-cell lymphoma, scleroderma, psoriasis, pemphigus vulgaris, atopic dermatitis, graft-versus-host disease, Crohn's disease, nephrogenic systemic fibrosis, and solid organ rejection in heart, lung, and liver transplantation. In this review, we aim to explore the proposed effects of extracorporeal photopheresis and to summarize published data on its use as a prophylactic and therapy in heart transplant rejection.

COVID-19 in hospitalized liver transplant recipients: An early systematic review and meta-analysis.

Abstract: Adverse clinical outcomes related to SARS-CoV-2 infection among liver transplant (LTx) recipients remain undefined We performed a meta-analysis to determine the pooled prevalence of outcomes among hospitalized LTx recipients with COVID-19 A database search of literature published between December 1, 2019, and November 20, 2020, was performed per PRISMA guidelines Twelve studies comprising 517 hospitalized LTx recipients with COVID-19 were analyzed Common presenting symptoms were fever (71%), cough (62%), dyspnea (48%), and diarrhea (28%) Approximately 77% (95% CI, 61%-93%) of LTx recipients had a history of liver cirrhosis The most prevalent comorbidities were hypertension (55%), diabetes (45%), and cardiac disease (21%) In-hospital mortality was 20% (95% CI, 13%-28%) and rose to 41% (95% CI, 19%-63%) (P 60-65 years) (OR 426; 95% CI, 214-849) There was no correlation in respect to sex or time since transplant In summary, LTx recipients with COVID-19 had a high prevalence of dyspnea and gastrointestinal symptoms In-hospital mortality was comparable to non-transplant populations with similar comorbidities but appeared to be less than what is reported elsewhere for cirrhotic patients (26%-40%) Importantly, the observed high case fatality in the elderly could be due to age-associated comorbidities

Lung transplantation for the treatment of irreversible acute respiratory distress syndrome

Abstract: Background Despite advances in critical care for acute respiratory distress syndrome (ARDS), some survivors in the acute phase are unable to wean from extracorporeal membrane oxygenation (ECMO) or mechanical ventilation. To date, little is known regarding whether lung transplantation confers a survival benefit for irreversible ARDS. Methods This retrospective study was conducted using the United Network for Organ Sharing database (May 2005-December 2018). Patients with restrictive lung disease were divided into two groups: patients with and without ARDS. Propensity score matching identified recipients without ARDS for the control group. Results A total of 63 patients with ARDS were waitlisted for lung transplantation, while 39 received a lung transplant after a median waitlist duration of 8 days. Seventy-eight patients were matched as controls. In the ARDS group, the median age was 30 years, and the median lung allocation score was 88.4. Among the 39 recipients, 30 (76.9%) received ECMO support prior to transplantation. Lung transplantation for ARDS and restrictive lung disease showed similar 90-day (87.2% vs. 88.5%, p = .80), 1-year (82.1% vs. 85.9%, p = .52), and 3-year (69.2% vs. 65.4%, p = .94) survival rates. Conclusions Lung transplantation provides acceptable outcomes in selected patients with irreversible ARDS.

Gut microbiota profiles and fecal beta-glucuronidase activity in kidney transplant recipients with and without post-transplant diarrhea

Abstract: Post-transplant diarrhea is a common complication after solid organ transplantation and is frequently attributed to the widely prescribed immunosuppressant mycophenolate mofetil (MMF). Given recent work identifying the relationship between MMF toxicity and gut bacterial β-glucuronidase activity, we evaluated the relationship between gut microbiota composition, fecal β-glucuronidase activity, and post-transplant diarrhea. We recruited 97 kidney transplant recipients and profiled the gut microbiota in 273 fecal specimens using 16S rRNA gene sequencing. We further characterized fecal β-glucuronidase activity in a subset of this cohort. Kidney transplant recipients with post-transplant diarrhea had decreased gut microbial diversity and decreased relative gut abundances of 12 genera when compared to those without post-transplant diarrhea (adjusted p value < .15, Wilcoxon rank sum test). Among the kidney transplant recipients with post-transplant diarrhea, those with higher fecal β-glucuronidase activity had a more prolonged course of diarrhea (≥7 days) compared to patients with lower fecal β-glucuronidase activity (91% vs 40%, p = .02, Fisher's exact test). Our data reveal post-transplant diarrhea as a complex phenomenon with decreased gut microbial diversity and commensal gut organisms. This study further links commensal bacterial metabolism with an important clinical outcome measure, suggesting fecal β-glucuronidase activity could be a novel biomarker for gastrointestinal-related MMF toxicity.

Histopathologic findings on indication renal allograft biopsies after recovery from acute COVID-19.

Abstract: Current knowledge on histopathological changes occurring after COVID-19 in transplanted kidneys is limited. Herein, we present renal allograft pathology findings in patients recovered from COVID-19. Six patients underwent indication biopsy, and one required allograft nephrectomy after acute COVID-19. Demographic data, clinical characteristics, and laboratory findings were recorded. The histopathological analysis included light microscopy, immunostaining, and electron microscopy. Five patients were hospitalized for acute COVID-19, and all were diagnosed with imaging-confirmed pneumonia, one requiring mechanical ventilation, and two requiring dialysis. Two patients had mild form. Histopathologic examination of renal allograft specimens revealed collapsing, perihilar, tip-lesion and secondary FSGS in one patient each. One patient had borderline acute cellular rejection, and two had chronic antibody-mediated rejection. Histopathologic changes of glomerular tufts were accompanied by acute tubular injury in four patients. None of our patients had signs of viral inclusions in kidney cells. One patient died and one remained dialysis-dependent after the good initial response to treatment. Patients with collapsing and perihilar FSGS had further progression of their chronic allograft nephropathy still without need for dialysis. In conclusion, diverse kidney pathology may be found in SARS-CoV-2-infected renal transplant patients. It seems that viral infection may affect the immune system with triggering of glomerular diseases, while the acute tubular injury is of multifactorial etiology. Direct viral effect is less likely.

Removal of the Black race coefficient from the estimated glomerular filtration equation improves transplant eligibility for Black patients at a single center.

Abstract: Race is a social construct that cannot be measured, can be used imprecisely and may contribute to disparities in kidney transplant access for Black patients. At Beth Israel Deaconess Medical Center, we dropped the Black race coefficient in the estimated glomerular filtration rate (eGFR) report in 2017. We conducted a quality improvement project to examine the impact of this change. Before the change, only 26% of our Black patients were listed for preemptive transplant compared to 70% of White patients. Since the change, we found a steady increase in the percentage of Black patients listed before starting dialysis. The average eGFR at listing prior to 2017 was significantly lower in Black patients but after, there was no longer a significant difference. 9 patients "gained" an average of 457 days of wait time directly related to discarding the Black race coefficient. Increased time on the list prior to dialysis initiation allows for evaluation of potential live donors and improves the possibility of a pre-emptive live or deceased donor transplant and allows for a shorter period on dialysis before transplant. In this single center initiative, we demonstrate the benefit of discarding race from the eGFR report for Black patients awaiting kidney transplantation. This article is protected by copyright. All rights reserved.

The incidence, clinical outcome, and protective factors of mixed chimerism following hematopoietic stem cell transplantation for severe aplastic anemia.

Abstract: OBJECTIVES The aim of our study was to determine possible predictors and clinical course of mixed chimerism (MC) in aplastic anemia after transplantation. METHODS A total of 207 transplants were obtained from haploidentical donors (HID) using busulfan (Bu), cyclophosphamide (Cy), and anti-thymocyte globulin (ATG) regimens, and 69 transplants from matched related donors (MRD) and 29 transplants from unrelated donors (URD) using Cy/ATG regimens were obtained. RESULTS Incidences of MC were 1.93 ± 0.01%, 20.29 ± 0.01%, and 35.71 ± 0.01% in HID, MRD, and URD transplantation (p < .001). In multivariate analysis, incidence of MC was significantly higher in patients without adding Bu in conditioning (p < .001) and receiving a lower number of CD3 + cells in graft (p = .042). MC was associated with significantly lower II-IV aGvHD (3.70% vs. 27.7%, p = .007), but higher secondary graft rejection rates (14.8% vs. 0.4%, p < .001) and poorer overall survival (72.7 ± 8.9% vs. 89.6 ± 2.0%, p = .011) than those of donor chimerism cohort. CONCLUSIONS Mixed chimerism was an unsettling status even in non-malignancy. Haploidentical transplantation with more intense regimen by adding Bu to Cy and ATG was associated with reduced MC following HSCT for SAA. An intensified regimen should be explored in matched related or unrelated donors.

Immunosuppression practices during the COVID-19 pandemic: a multinational survey study of transplant programs

Abstract: During the COVID-19 pandemic, there has been wide heterogeneity in the medical management of transplant recipients. We aimed to pragmatically capture immunosuppression practices globally following the early months of the pandemic. From June to September 2020, we surveyed 1267 physicians; 40.5% from 71 countries participated. Management decisions were made on a case-by-case basis by the majority (69.6%) of the programs. Overall, 76.8% performed ≥1 transplantation and many commented on avoiding high-risk transplantations. For induction, 26.5% were less likely to give T-cell depletion and 14.8% were more likely to give non-depleting agents. These practices varied by program-level factors more so than the COVID-19 burden. In patients with mild, moderate and severe COVID-19 symptoms 59.7%, 76.0%, and 79.5% decreased/stopped anti-metabolites, 23.2%, 45.4%, and 68.2% decreased/stopped calcineurin inhibitors, and 25.7%, 43.9%, and 57.7% decreased/stopped mTOR inhibitors, respectively. Also, 2.1%, 30.6%, and 46.0% increased steroids in patients with mild, moderate, and severe COVID-19 symptoms. For prevalent transplant recipients, some programs also reported decreasing/stopping steroids (1.8%), anti-metabolites (10.3%), calcineurin inhibitors (4.1%), and mTOR inhibitors (5.5%). Transplant programs changed immunosuppression practices but also avoided high-risk transplants and increased maintenance steroids. The long-term ramifications of these practices remain to be seen as programs face the aftermath of the pandemic.

Evolving utilization of donation after circulatory death livers in liver transplantation: The day of DCD has come

Abstract: Compared to donation after brain death (DBD), livers procured for transplantation from donation after circulatory death (DCD) donors experience more ischemia-reperfusion injury and higher rates of ischemic cholangiopathy due to the period of warm ischemic time (WIT) following withdrawal of life support. As a result, utilization of DCD livers for liver transplant (LT) has generally been limited to short WITs and younger aged donor grafts, causing many recovered DCD organs to be discarded without consideration for transplant. This study assesses how DCD liver utilization and outcomes have changed over time, using OPTN data from adult, first-time, deceased donor, whole-organ LTs between January 1995 and December 2019. Results show that increased clinical experience with DCD LT has translated into increased use of livers from DCD donors, shorter ischemic times, shorter lengths of hospitalization after transplant, and lower rates of retransplantation. The data also reveal that over the past decade, the rate of increase in DCD LTs conducted in the United States has outpaced that of DBD. Together, these trends signal an opportunity for the field of liver transplantation to mitigate the organ shortage by capitalizing on DCD liver allografts that are currently not being utilized.

Impact of pre-transplant carbapenem-resistant Enterobacterales colonization and/or infection on solid organ transplant outcomes.

Abstract: The impact of pre-transplant (SOT) carbapenem-resistant Enterobacterales (CRE) colonization or infection on post-SOT outcomes is unclear. We conducted a multi-center, international, cohort study of SOT recipients, with microbiologically diagnosed CRE colonization and/or infection pre-SOT. Sixty adult SOT recipients were included (liver n = 30, hearts n = 17). Klebsiella pneumoniae (n = 47, 78%) was the most common pre-SOT CRE species. Median time from CRE detection to SOT was 2.32 months (IQR 0.33-10.13). Post-SOT CRE infection occurred in 40% (n = 24/60), at a median of 9 days (IQR 7-17), and most commonly due to K pneumoniae (n = 20/24, 83%). Of those infected, 62% had a surgical site infection, and 46% had bloodstream infection. Patients with post-SOT CRE infection more commonly had a liver transplant (16, 67% vs. 14, 39%; p =.0350) or pre-SOT CRE BSI (11, 46% vs. 7, 19%; p =.03). One-year post-SOT survival was 77%, and those with post-SOT CRE infection had a 50% less chance of survival vs. uninfected (0.86, 95% CI, 0.76-0.97 vs. 0.34, 95% CI 0.08-1.0, p =.0204). Pre-SOT CRE infection or colonization is not an absolute contraindication to SOT and is more common among abdominal SOT recipients, those with pre-SOT CRE BSI, and those with early post-SOT medical and surgical complications.

Operational challenges in the COVID era: Asymptomatic infections and vaccination timing.

Abstract: The coronavirus disease 2019 (COVID-19) pandemic has created unprecedented challenges for solid organ transplant programs. While transplant activity has largely recovered, appropriate management of deceased donor candidates who are asymptomatic but have positive nucleic acid test (NAT) for COVID-19 is unclear as this may reflect active infection or prolonged viral shedding. Furthermore, candidates who are unvaccinated or partially vaccinated continue to receive donor offers. In the absence of prospective data, transplant professionals at U.S. adult kidney transplant centers were surveyed to determine community practice (N: 92 centers, capturing 40.8% of centers and 56.6% of transplants performed). The majority (96.8%) of responding centers declined organs for asymptomatic NAT+ patients without documented prior infection. However, 31.6% of centers proceeded with kidney transplant in NAT+ patients who were at least 30 days from initial diagnosis with negative chest imaging. Less than 7% of programs reported inactivating patients who were unvaccinated or partially vaccinated. In conclusion, despite national recommendations to wait for negative testing, many centers are proceeding with transplant in patients with positive tests due to presumed viral shedding. Furthermore, very few centers are requiring COVID-19 vaccination prior to transplantation despite early evidence suggesting reduced immunogenicity in transplant patients on immunosuppression. This article is protected by copyright. All rights reserved.

SARS-CoV-2 infection increases tacrolimus concentrations in solid-organ transplant recipients.

Abstract: Calcineurin inhibitors (CNI) are narrow therapeutic index medications, with drug concentrations altered by factors such as drug-drug interactions, clinical symptoms including diarrhea, and hepatic dysfunction. Supratherapeutic CNI concentrations can produce a myriad of toxicities, the most worrisome of which are renal injury and seizures.