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Durability of variant neutralization in solid organ transplant recipients following Omicron-containing boosters is unknown. We report wane in XBB.1.5 neutralization by 3 months following a first bivalent booster, improved by a second booster; hybrid immunity improved peak, and duration of neutralization. Boosting at 3 to 6 months appears necessary to maintain neutralization.
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Obesity is a chronic, relapsing disease that increases the risks of living kidney donation; at the same time, transplant centers have liberalized body mass index constraints for donors. With the increasing number of antiobesity medications available, the treatment of obesity with antiobesity medications may increase the pool of potential donors and enhance donor safety. Antiobesity medications are intended for long-term use given the chronic nature of obesity. Cessation of treatment can be expected to lead to weight regain and increase the risk of comorbidity rebound/development. In addition, antiobesity medications are meant to be used in conjunction with-rather than in replacement of-diet and physical activity optimization. Antiobesity medication management includes selecting medications that may ameliorate any coexisting medical conditions, avoiding those that are contraindicated in such conditions, and being sensitive to any out-of-pocket expenses that may be incurred by the potential donor. A number of questions remain regarding who will and should shoulder the costs of long-term obesity treatment for donors. In addition, future studies are needed to quantify the degree of weight loss and duration of weight loss maintenance needed to normalize the risk of adverse kidney outcomes relative to comparable nondonors and lower-weight donors.
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Doadores de Tecidos , Coleta de Tecidos e Órgãos , Humanos , Rim , Obesidade/tratamento farmacológico , Redução de PesoRESUMO
The first 2 living recipients of pig hearts died unexpectedly within 2 months, despite both recipients receiving what over 30 years of nonhuman primate (NHP) research would suggest were the optimal gene edits and immunosuppression to ensure success. These results prompt us to question how faithfully data from the NHP model translate into human outcomes. Before attempting any further heart xenotransplants in living humans, it is highly advisable to gain a more comprehensive understanding of why the promising preclinical NHP data did not accurately predict outcomes in humans. It is also unlikely that additional NHP data will provide more information that would de-risk a xenoheart clinical trial because these cases were based on the best practices from the most successful NHP results to date. Although imperfect, the decedent model offers a complementary avenue to determine appropriate treatment regimens to control the human immune response to xenografts and better understand the biologic differences between humans and NHP that could lead to such starkly contrasting outcomes. Herein, we explore the potential benefits and drawbacks of the decedent model and contrast it to the advantages and disadvantages of the extensive body of data generated in the NHP xenoheart transplantation model.
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Terapia de Imunossupressão , Humanos , Animais , Suínos , Transplante Heterólogo , XenoenxertosRESUMO
Graft failure and recipient death with functioning graft are important competing outcomes after kidney transplantation. Risk prediction models typically censor for the competing outcome thereby overestimating the cumulative incidence. The magnitude of this overestimation is not well-described in real-world transplant data. This retrospective cohort study analyzed data from the European Collaborative Transplant Study (CTS; n = 125 250) and from the American Scientific Registry of Transplant Recipients (SRTR; n = 190 258). Separate cause-specific hazard models, using donor and recipient age as continuous predictors, were developed for graft failure and recipient death. The hazard of graft failure increased quadratically with increasing donor age and decreased decaying with increasing recipient age. The hazard of recipient death increased linearly with increasing donor and recipient age. The cumulative incidence overestimation due to competing risk-censoring was largest in high-risk populations for both outcomes (old donors/recipients), sometimes amounting to 8.4 and 18.8 percentage points for graft failure and recipient death, respectively. In our illustrative model for post-transplant risk prediction, the absolute risk of graft failure and death is overestimated when censoring for the competing event, mainly in older donors and recipients. Prediction models for absolute risks should treat graft failure and death as competing events.
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Body mass index is often used to determine kidney transplant (KT) candidacy. However, this measure of body composition (BC) has several limitations, including the inability to accurately capture dry weight. Objective computed tomography (CT)-based measures may improve pre-KT risk stratification and capture physiological aging more accurately. We quantified the association between CT-based BC measurements and waitlist mortality in a retrospective study of 828 KT candidates (2010-2022) with clinically obtained CT scans using adjusted competing risk regression. In total, 42.5% of candidates had myopenia, 11.4% had myopenic obesity (MO), 68.8% had myosteatosis, 24.8% had sarcopenia (probable = 11.2%, confirmed = 10.5%, and severe = 3.1%), and 8.6% had sarcopenic obesity. Myopenia, MO, and sarcopenic obesity were not associated with mortality. Patients with myosteatosis (adjusted subhazard ratio [aSHR] = 1.62, 95% confidence interval [CI]: 1.07-2.45; after confounder adjustment) or sarcopenia (probable: aSHR = 1.78, 95% CI: 1.10-2.88; confirmed: aSHR = 1.68, 95% CI: 1.01-2.82; and severe: aSHR = 2.51, 95% CI: 1.12-5.66; after full adjustment) were at increased risk of mortality. When stratified by age, MO (aSHR = 2.21, 95% CI: 1.28-3.83; P interaction = .005) and myosteatosis (aSHR = 1.95, 95% CI: 1.18-3.21; P interaction = .038) were associated with elevated risk only among candidates <65 years. MO was only associated with waitlist mortality among frail candidates (adjusted hazard ratio = 2.54, 95% CI: 1.28-5.05; P interaction = .021). Transplant centers should consider using BC metrics in addition to body mass index when a CT scan is available to improve pre-KT risk stratification at KT evaluation.
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Transplante de Rim , Sarcopenia , Humanos , Sarcopenia/diagnóstico por imagem , Sarcopenia/etiologia , Medição de Risco/métodos , Estudos Retrospectivos , Obesidade , Atrofia Muscular , Tomografia Computadorizada por Raios X , Composição CorporalRESUMO
This chapter updates the COVID-19 chapter from the 2021 Annual Data Report with trends through November 12, 2022, and introduces trends in recovery and use of organs from donors with a positive COVID-19 test. Posttransplant mortality and graft failure, which remained a concern in all organs at the last report due to the Omicron variant wave, have returned to lower levels in the most recent available data through November 2022. Use of organs from donors with a positive COVID-19 test has grown, particularly after the first year of the pandemic. Mortality due to COVID-19 should continue to be monitored, but most other measures have sustained their recovery and may now be responding more to changes in policy than to ongoing concerns with COVID-19.
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COVID-19 , Obtenção de Tecidos e Órgãos , Humanos , Estados Unidos/epidemiologia , Sobrevivência de Enxerto , Listas de Espera , SARS-CoV-2 , Doadores de TecidosRESUMO
Kidney transplantation from blood type A2/A2B donors to type B recipients (A2âB) has increased dramatically under the current Kidney Allocation System (KAS). Among living donor transplant recipients, A2-incompatible transplants are associated with an increased risk of all-cause and death-censored graft failure. In light of this, we used data from the Scientific Registry of Transplant Recipients from December 2014 until June 2022 to evaluate the association between A2âB listing and time to deceased donor kidney transplantation (DDKT) and post-DDKT outcomes for A2âB recipients. Among 53 409 type B waitlist registrants, only 12.6% were listed as eligible to accept A2âB offers ("A2-eligible"). The rates of DDKT at 1-, 3-, and 5-years were 32.1%, 61.4%, and 72.1% among A2-eligible candidates and 14.1%, 29.9%, and 44.1% among A2-ineligible candidates, with the former experiencing a 133% higher rate of DDKT (Cox weighted hazard ratio (wHR) = 2.192.332.47; P < .001). The 7-year adjusted mortality was comparable between A2âB and B-ABOc (type B/O donors to B recipients) recipients (wHR 0.780.941.13, P = .5). Moreover, there was no difference between A2âB vs B-ABOc DDKT recipients with regards to death-censored graft failure (wHR 0.771.001.29, P > .9) or all-cause graft loss (wHR 0.820.961.12, P = .6). Following its broader adoption since the implementation of the kidney allocation system, A2âB DDKT appears to be a safe and effective transplant modality for eligible candidates. As such, A2âB listing for eligible type B candidates should be expanded.
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Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Doadores de Tecidos , Doadores Vivos , Transplantados , Sistema de Registros , Rim , Sobrevivência de EnxertoRESUMO
RATIONALE & OBJECTIVE: Because of the high risk of waitlist mortality and posttransplant complications, kidney transplant (KT) patients may benefit from advance care planning (ACP) and palliative care consultation (PCC). We quantified the prevalence and racial disparities in ACP and PCC among KT candidates and recipients. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 2,575 adult KT candidates and 1,233 adult recipients (2008-2020). EXPOSURE: Race and ethnicity. OUTCOMES: All reports of ACP and PCC were abstracted from chart review. ACP was defined as patient self-report of an advance directive, presence of an advance directive in the medical record, or a documented goals-of-care conversation with a provider. PCC was defined as an ordered referral or a documented palliative care note in the medical record. ANALYTICAL APPROACH: Racial/ethnic disparities in ACP/PCC were estimated using adjusted logistic regression. RESULTS: 21.4% of KT candidates and 34.9% of recipients engaged in ACP. There were racial/ethnic disparities in ACP among KT candidates (White, 24.4%; Black, 19.1%; Hispanic, 15%; other race and ethnicity, 21.1%; P=0.008) and recipients (White, 39.5%; Black, 31.2%; Hispanic, 26.3%; other race and ethnicity, 26.6%; P=0.007). After adjustment, Black KT recipients had a 29% lower likelihood of engaging in ACP (OR, 0.71; 95% CI, 0.55-0.91) than White KT recipients. Among older (aged≥65 years) recipients, those who were Black had a lower likelihood of engaging in ACP, but there was no racial disparity among younger recipients (P=0.020 for interaction). 4.2% of KT candidates and 5.1% of KT recipients engaged in PCC; there were no racial disparities in PCC among KT candidates (White, 5.3%; Black, 3.6%; Hispanic, 2.5%; other race and ethnicity, 2.1%; P=0.13) or recipients (White, 5.5%; Black, 5.6%; Hispanic, 0.0%; other race and ethnicity, 1.3%; P = 0.21). LIMITATIONS: Generalizability may be limited to academic transplant centers. CONCLUSIONS: ACP is not common among KT patients, and minoritized transplant patients are least likely to engage in ACP; PCC is less common. Future efforts should aim to integrate ACP and PCC into the KT process. PLAIN-LANGUAGE SUMMARY: Kidney transplant (KT) candidates and recipients are at elevated risk of morbidity and mortality. They may benefit from completing a document or conversation with their palliative care provider that outlines their future health care wishes, known as advance care planning (ACP), which is a component of palliative care consultation (PCC). We wanted to determine how many KT candidates and recipients have engaged in ACP or PCC and identify potential racial disparities. We found that 21.4% of candidates and 34.9% of recipients engaged in ACP. After adjustment, Black recipients had a 29% lower likelihood of engaging in ACP. We found that 4.2% of KT candidates and 5.1% of KT recipients engaged in PCC, with no racial disparities found in PCC.
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Planejamento Antecipado de Cuidados , Transplante de Rim , Cuidados Paliativos , Adulto , Humanos , Negro ou Afro-Americano , Estudos Prospectivos , Encaminhamento e Consulta , População Branca , Hispânico ou LatinoRESUMO
OBJECTIVE: Incidence and manifestations of postacute sequelae of coronavirus disease 2019 (PASC) are poorly defined among immunosuppressed populations. We reported, phenotyped, and assessed risk factors for PASC in adults with systemic autoimmune diseases. METHODS: Persons aged ≥ 18 years with systemic autoimmune diseases were recruited into a national, prospective observational cohort of SARS-CoV-2 vaccination and infection between December 2020 and April 2021. Serial surveys assessed vaccination status, SARS-CoV-2 infection incidence, and disease flares. Participants reporting SARS-CoV-2 infection received a questionnaire assessing symptom duration, severity, and quality of life (QOL) effect; PASC was defined as ≥ 1 symptom persisting for > 12 weeks. PASC syndromes were mapped by overlapping symptom domains. Characteristics were compared between participants who did vs did not report PASC. RESULTS: Among 1615 participants, 590 (36.5%) reported SARS-CoV-2 infection and were sent PASC surveys, 299 (50.7%) of whom responded > 12 weeks following the reported infection. Respondents were 91.6% female, 91.2% White, median (IQR) age was 48 (40-60) years with median (IQR) 3 (2-3) vaccine doses at time of first infection. Common diagnoses included inflammatory arthritis (38.5%) and inflammatory bowel disease (14.4%). Eighty-nine of 299 (29.8%) reported PASC, with the most reported symptom domain being neurological/psychological (83.1%); 84% reported an effect on QOL. Participants with PASC reported lower number of preceding vaccines (median [IQR] 2 [2-3] vs 3 [2-3]; P < 0.001) and more reinfections (16.9% vs 5.7%; P = 0.004). CONCLUSION: In a large, real-world cohort, 29.8% of persons with systemic autoimmune disease reported PASC, often affecting QOL. Preceding vaccination may reduce PASC, whereas multiple infections may increase risk, supporting ongoing booster vaccine campaigns and efforts to limit breakthrough infections.
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INTRODUCTION: Transplants with hearts and lungs from donors with hepatitis C virus (HCV D+) have been proven safe and effective since development of direct-acting antivirals, yet the presence of HCV + persists as a reason to decline organs. METHODS: We identified adult candidates listed January 1, 2015-March 8, 2023 for heart or lung transplant using the Scientific Registry of Transplant Recipients. We identified individual-level and center-level characteristics associated with listing to consider HCV D+ offers using multilevel logistic regression in a multivariable framework. RESULTS: Over the study period, the annual percentage of candidates willing to consider HCV D+ offers increased for both heart (9.5%-74.3%) and lung (7.8%-59.5%), as did the percentage of centers listing candidates for HCV D+ heart (52.9%-91.1%) and lung (32.8%-82.8%) offers. Candidates at centers with more experience with HCV D+ transplants were more likely to consider HCV D+ organ offers. After adjustment, listing center explained 70% and 78% of the residual variance in willingness to consider HCV D+ hearts and lungs, respectively. CONCLUSIONS: Although listing for consideration of HCV D+ offers has increased, it varies by transplant center. Center-level barriers to consideration of HCV D+ organs reduce recipients' transplant access.
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BACKGROUND: Recent clinical trials demonstrate benefits of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in patients with chronic kidney disease, but data on use in kidney transplant (KTx) recipients are limited. METHODS: We examined a novel database linking SRTR registry data for KTx recipients (2000-2021) with outpatient fill records from a large pharmaceutical claims warehouse (2015-2021). Adult (≥18 years) KTx recipients treated with SGLT2i were compared to those who received other noninsulin diabetes medications without SGLT2i. Characteristics associated with SGLT2i use were quantified by multivariable logistic regression (adjusted odds ratio, 95%LCLaOR95%UCL). RESULTS: Among 18 988 KTx recipients treated with noninsulin diabetes agents in the study period, 2224 filled an SGLT2i. Mean time from KTx to prescription was 6.7 years for SGLT2i versus 4.7 years for non-SGLT2i medications. SGLT2i use was more common in Asian adults (aOR, 1.091.311.58) and those aged > 30-59 years (compared with 18-30 years) or with BMI > 35 kg/m2 (aOR, 1.191.411.67), and trended higher with self-pay status. SGLT2i use was lower among KTx recipients who were women (aOR, .79.87.96), Black (aOR, .77.881.00) and other (aOR, .52.751.07) race, publicly insured (aOR, .82.921.03), or with less than college education (aOR, .78.87.96), and trended lower in those age 75 years and older. SGLT2i use in KTx patients increased dramatically in 2019-2021 (aOR, 5.015.636.33 vs. prior years). CONCLUSION: SGLT2i use is increasing in KTx recipients but varies with factors including race, education, and insurance. While ongoing study is needed to define risks and benefits of SGLT2i use in KTx patients, attention should also focus on reducing treatment disparities related to sociodemographic traits.
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Diabetes Mellitus Tipo 2 , Transplante de Rim , Farmácia , Inibidores do Transportador 2 de Sódio-Glicose , Adulto , Humanos , Feminino , Masculino , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Transplante de Rim/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/etiologia , Glucose , Sódio/uso terapêutico , Hipoglicemiantes/uso terapêuticoRESUMO
INTRODUCTION: Adults residing in deprived neighborhoods face various socioeconomic stressors, hindering their likelihood of receiving live-donor kidney transplantation (LDKT) and preemptive kidney transplantation (KT). We quantified the association between residential neighborhood deprivation index (NDI) and the likelihood of LDKT/preemptive KT, testing for a differential impact by race and ethnicity. METHODS: We studied 403 937 adults (age ≥ 18) KT candidates (national transplant registry; 2006-2021). NDI and its 10 components were averaged at the ZIP-code level. Cause-specific hazards models were used to quantify the adjusted hazard ratio (aHR) of LDKT and preemptive KT across tertiles of NDI and its 10 components. RESULTS: Candidates residing in high-deprivation neighborhoods were more likely to be female (40.1% vs. 36.2%) and Black (41.9% vs. 17.7%), and were less likely to receive both LDKT (aHR = 0.66, 95% confidence interval [CI]: 0.64-0.67) and preemptive KT (aHR = 0.60, 95% CI: 0.59-0.62) than those in low-deprivation neighborhoods. These associations differedby race and ethnicity (Black: aHRLDKT = 0.58, 95% CI: 0.55-0.62; aHRpreemptive KT = 0.68, 95% CI: 0.63-0.73; Pinteractions: LDKT < 0.001; Preemptive KT = 0.002). All deprivation components were associated with the likelihood of both LDKT and preemptive KT (except median home value): for example, higher median household income (LDKT: aHR = 1.08, 95% CI: 1.07-1.09; Preemptive KT: aHR = 1.10, 95% CI: 1.08-1.11) and educational attainments (≥high school [LDKT: aHR = 1.17, 95% CI: 1.15-1.18; Preemptive KT: aHR = 1.23, 95% CI: 1.21-1.25]). CONCLUSION: Residence in socioeconomically deprived neighborhoods is associated with a lower likelihood of LDKT and preemptive KT, differentially impacting minority candidates. Identifying and understanding which neighborhood-level socioeconomic status contributes to these racial disparities can be instrumental in tailoring interventions to achieve health equity in LDKT and preemptive KT.
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Transplante de Rim , Doadores Vivos , Características da Vizinhança , Humanos , Feminino , Masculino , Doadores Vivos/provisão & distribuição , Pessoa de Meia-Idade , Adulto , Seguimentos , Prognóstico , Características de Residência , Falência Renal Crônica/cirurgia , Fatores Socioeconômicos , Sistema de Registros/estatística & dados numéricos , Fatores de Risco , Adulto Jovem , AdolescenteRESUMO
BACKGROUND: Medical distrust may hinder kidney transplantation (KT) access. Among KT candidates evaluated for waitlisting, we identified factors associated with high distrust levels and quantified their association with waitlisting. METHODS: Among 812 candidates (2018-2023), we assessed distrust using the Revised Health Care System Distrust Scale across composite, competence, and values subscales. We used linear regression to quantify the associations between candidate and neighborhood-level factors and distrust scores. We used Cox models to quantify the associations between distrust scores and waitlisting. RESULTS: At KT evaluation, candidates who were aged 35-49 years (difference = 1.97, 95% CI: 0.78-3.16), female (difference = 1.10, 95% CI: 0.23-1.97), and Black (difference = 1.47, 95% CI: 0.47-2.47) were more likely to report higher composite distrust score. For subscales, candidates aged 35-49 were more likely to have higher competence distrust score (difference = 1.14, 95% CI: 0.59-1.68) and values distrust score (difference = 0.83, 95% CI: 0.05-1.61). Race/ethnicity (Black, difference = 1.42, 95% CI: 0.76-2.07; Hispanic, difference = 1.52, 95% CI: 0.35-2.69) was only associated with higher values distrust scores. Female candidates reporting higher rescaled values distrust scores (each one point) had a lower chance of waitlisting (aHR = 0.78, 95% CI: 0.63-0.98), whereas this association was not observed among males. Similarly, among non-White candidates, each 1-point increase in both rescaled composite (aHR = 0.87, 95% CI: 0.77-0.99) and values (aHR = 0.82, 95% CI: 0.68-0.99) distrust scores was associated with a lower chance of waitlisting, while there was no association among White candidates. CONCLUSION: Female, younger, and non-White candidates reported higher distrust scores. Values distrust may contribute to the long-standing racial/ethnic and gender disparities in access to KT. Implementing tailored strategies to reduce distrust in transplant care may improve KT access for groups that experience persistent disparities.
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Transplante de Rim , Confiança , Listas de Espera , Humanos , Feminino , Masculino , Transplante de Rim/psicologia , Pessoa de Meia-Idade , Adulto , Prognóstico , Seguimentos , Falência Renal Crônica/cirurgia , Falência Renal Crônica/psicologiaRESUMO
BACKGROUND: Patients with obesity have inferior outcomes after general surgery procedures, but studies evaluating post-liver transplant (LT) outcomes have been limited by small sample sizes or lack of granularity of outcomes. We evaluated the relationship between obesity and post-LT outcomes, including those observed in other populations to be obesity-related. METHODS: Included were 1357 LT recipients prospectively enrolled in the ambulatory pre-LT setting at 8 U.S. CENTERS: Recipient were categorized by body mass index (BMI, kg/m2 ): non-obese (BMI < 30), class 1 obesity (BMI 30-<35), and classes 2-3 obesity (BMI ≥ 35). Post-transplant complications were compared by BMI using Chi-square and rank-sum testing, logistic regression, Kaplan-Meier curves, and Cox regression. RESULTS: Classes 2-3 obesity was associated with higher adjusted odds than non-obesity of venous thrombosis [adjusted odds ratio (aOR) 2.06, 95% CI 1.01-4.23, p = .047] and wound dehiscence (aOR 2.45, 95% CI 1.19-5.06, p = .02). Compared with non-obese recipients, post-LT hospital stay was significantly longer for recipients with classes 2-3 obesity [p = .01; median (Q1-Q3) 9 (6-14) vs. 8 (6-12) days) or class 1 obesity [p = .002; 9 (6-14) vs. 8 (6-11) days]. Likelihood of ICU readmission, infection, discharge to a non-home facility, rejection, 30-day readmission, and 1-year readmission were similar across BMI categories (all p > .05). CONCLUSION: Compared to non-obese recipients, obese recipients had similar post-LT survival but longer hospital stay and higher likelihood of wound dehiscence and venous thrombosis. These findings underscore that obesity alone should not preclude LT, but recipients with obesity should be monitored for obesity-related complications such as wound dehiscence and venous thrombosis.
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Transplante de Fígado , Trombose Venosa , Humanos , Índice de Massa Corporal , Transplante de Fígado/efeitos adversos , Obesidade/etiologia , Complicações Pós-Operatórias/etiologia , Trombose Venosa/complicações , Estudos Retrospectivos , Resultado do Tratamento , Fatores de RiscoRESUMO
INTRODUCTION: Thoracoabdominal normothermic regional perfusion (TA-NRP) following cardiac death is an emerging multivisceral organ procurement technique. Recent national studies on outcomes of presumptive TA-NRP-procured organs are limited by potential misclassification since TA-NRP is not differentiated from donation after cardiac death (DCD) in registry data. METHODS: We studied 22 donors whose designees consented to TA-NRP and organ procurement performed at our institution between January 20, 2020 and July 3, 2022. We identified these donors in SRTR to describe organ utilization and recipient outcomes and compared them to recipients of traditional DCD (tDCD) and donation after brain death (DBD) organs during the same timeframe. RESULTS: All 22 donors progressed to cardiac arrest and underwent TA-NRP followed by heart, lung, kidney, and/or liver procurement. Median donor age was 41 years, 55% had anoxic brain injury, 45% were hypertensive, 0% were diabetic, and median kidney donor profile index was 40%. TA-NRP utilization was high across all organ types (88%-100%), with a higher percentage of kidneys procured via TA-NRP compared to tDCD (88% vs. 72%, p = .02). Recipient and graft survival ranged from 89% to 100% and were comparable to tDCD and DBD recipients (p ≥ .2). Delayed graft function was lower for kidneys procured from TA-NRP compared to tDCD donors (27% vs. 44%, p = .045). CONCLUSION: Procurement from TA-NRP donors yielded high organ utilization, with outcomes comparable to tDCD and DBD recipients across organ types. Further large-scale study of TA-NRP donors, facilitated by its capture in the national registry, will be critical to fully understand its impact as an organ procurement technique.
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Benzidinas , Coração , Obtenção de Tecidos e Órgãos , Humanos , Adulto , Perfusão , Doadores de Tecidos , Morte EncefálicaRESUMO
BACKGROUND: Kidney transplant recipients (KTRs) generate lower antibody responses to messenger RNA (mRNA)-based severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination, yet precise mechanisms for this poor response remain uncertain. One potential contributor is suboptimal spike antigen (sAg) translation and expression owing to transplant immunosuppression, which might lead to insufficient exposure to develop humoral and/or cellular immune responses. METHODS: Within a single-arm clinical trial, 65 KTRs underwent ultrasensitive plasma sAg testing before, and 3 and 14 days after, the third mRNA vaccine doses. Anti-SARS-CoV-2 spike antibodies (anti-receptor binding domain [anti-RBD]) were serially measured at 14 and 30 days post-vaccination. Associations between sAg detection and clinical factors were assessed. Day 30 anti-RBD titer was compared among those with versus without sAg expression using Wilcoxon rank sum testing. RESULTS: Overall, 16 (25%) KTRs were sAg positive (sAg+) after vaccination, peaking at day 3. Clinical and laboratory factors were broadly similar in sAg(+) versus sAg(-) KTRs. sAg(+) status was significantly negatively associated with day 30 anti-RBD response, with median (interquartile range) 10.8 (<0.4-338.3) U/mL if sAg(+) versus 709 (10.5-2309.5) U/mL if sAg(-) (i.e., 66-fold lower; p = .01). CONCLUSION: Inadequate plasma sAg does not likely drive poor antibody responses in KTRs, rather sAg detection implies insufficient immune response to rapidly clear vaccine antigen from blood. Other downstream mechanisms such as sAg trafficking and presentation should be explored.
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Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Transplante de Rim , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Transplantados , Humanos , Transplante de Rim/efeitos adversos , Glicoproteína da Espícula de Coronavírus/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Anticorpos Antivirais/sangue , SARS-CoV-2/imunologia , COVID-19/prevenção & controle , COVID-19/imunologia , COVID-19/sangue , Vacinas contra COVID-19/imunologia , Adulto , Idoso , Formação de Anticorpos , Vacinação , Vacina BNT162/imunologiaRESUMO
Transplantation remains the gold-standard treatment for pediatric end-stage kidney disease. While living donor transplant is the preferred option for most pediatric patients, it is not the right choice for all. For those who have the option to choose between deceased donor and living donor transplantation, or from among multiple potential living donors, the transplant clinician must weigh multiple dynamic factors to identify the most optimal donor. This review will cover the key considerations when choosing between potential living donors and will propose a decision-making algorithm.
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Falência Renal Crônica , Transplante de Rim , Doadores Vivos , Humanos , Transplante de Rim/métodos , Falência Renal Crônica/cirurgia , Criança , Tomada de Decisões , Seleção do Doador/métodos , Tomada de Decisão Clínica , AlgoritmosRESUMO
BACKGROUND: Pediatric (age < 18 years) kidney transplant (KT) candidates face increasingly complex choices. The 2014 kidney allocation system nearly doubled wait times for pediatric recipients. Given longer wait times and new ways to optimize compatibility, more pediatric candidates may consider kidney-paired donation (KPD). Motivated by this shift and the potential impact of innovations in KPD practice, we studied pediatric KPD procedures in the US from 2008 to 2021. METHODS: We describe the characteristics and outcomes of pediatric KPD recipients with comparison to pediatric non-KPD living donor kidney transplants (LDKT), pediatric LDKT recipients, and pediatric deceased donor (DDKT) recipients. RESULTS: Our study cohort includes 4987 pediatric DDKTs, 3447 pediatric non-KPD LDKTs, and 258 pediatric KPD transplants. Fewer centers conducted at least one pediatric KPD procedure compared to those that conducted at least one pediatric LDKT or DDKT procedure (67, 136, and 155 centers, respectively). Five centers performed 31% of the pediatric KPD transplants. After adjustment, there were no differences in graft failure or mortality comparing KPD recipients to non-KPD LDKT, LDKT, or DDKT recipients. DISCUSSION: We did not observe differences in transplant outcomes comparing pediatric KPD recipients to controls. Considering these results, KPD may be underutilized for pediatric recipients. Pediatric KT centers should consider including KPD in KT candidate education. Further research will be necessary to develop tools that could aid clinicians and families considering the time horizon for future KT procedures, candidate disease and histocompatibility characteristics, and other factors including logistics and donor protections.
Assuntos
Transplante de Rim , Obtenção de Tecidos e Órgãos , Humanos , Estados Unidos , Criança , Adolescente , Doadores Vivos , Coleta de Tecidos e Órgãos , Transplante de Rim/métodos , Histocompatibilidade , RimRESUMO
BACKGROUND: Adolescent solid organ transplant recipients (aSOTRs) who received three doses of the COVID-19 mRNA vaccine experience high seroconversion rates and antibody persistence for up to 3 months. Long-term antibody durability beyond this timeframe following three doses of the SARS-CoV-2 mRNA vaccine remains unknown. We describe antibody responses 6 months following the third vaccine dose (D3) of the BNT162b2 mRNA vaccination among aSOTRs. METHODS: Participants in a multi-center, observational cohort who received the third dose of the vaccine were analyzed for antibodies to the SARS-CoV-2 spike protein receptor-binding domain (Roche Elecsys anti-SARS-CoV-2-S positive: ≥0.8, maximum: >2500 U/mL). Samples were collected at 1-, 3-, and 6-months post-D3. Participants were surveyed at each timepoint and at 12-months post-D3. RESULTS: All 34 participants had positive anti-RBD antibody titers 6 months post-D3. Variations in titers occurred between 3 and 6 months post-D3, with 8/28 (29%) having decreased antibody levels at 6 months compared to 3 months and 2/28 (7%) reporting increased titers at 6 months. The remaining 18/28 (64%) had unchanged antibody titers compared to 3-month post-D3 levels. A total of 4/34 (12%) reported breakthrough infection within 6 months and 3/32 (9%) reported infection after 6-12 months following the third dose of the SARS-CoV-2 mRNA vaccine. CONCLUSIONS: The results suggest that antibody durability persists up to 6 months following three doses of the SARS-CoV-2 mRNA in aSOTRs. Demography and transplant characteristics did not differ for those who experienced antibody weaning. Breakthrough infections did occur, reflecting immune-evasive nature of novel variants such as Omicron.
Assuntos
COVID-19 , Transplante de Órgãos , Glicoproteína da Espícula de Coronavírus , Adolescente , Humanos , Anticorpos , Anticorpos Antivirais , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Vacinas de mRNA , RNA Mensageiro , SARS-CoV-2 , Transplantados , Vacinação , Estudos de CoortesRESUMO
BACKGROUND: Though older adults with chronic kidney disease (CKD) have a greater mortality risk than those without CKD, traditional risk factors poorly predict mortality in this population. Therefore, we tested our hypothesis that two common geriatric risk factors, frailty and cognitive impairment, and their co-occurrence, might improve mortality risk prediction in CKD. METHODS: Among participants aged ≥ 60 years from National Health and Nutrition Examination Survey (2011-2014), we quantified associations between frailty (physical frailty phenotype) and global/domain-specific cognitive function (immediate-recall [CERAD-WL], delayed-recall [CERAD-DL], verbal fluency [AF], executive function/processing speed [DSST], and global [standardized-average of 4 domain-specific tests]) using linear regression, and tested whether associations differed by CKD using a Wald test. We then tested whether frailty, global cognitive impairment (1.5SD below the mean), or their combination improved prediction of mortality (Cox models, c-statistics) compared to base models (likelihood-ratios) among those with and without CKD. RESULTS: Among 3,211 participants, 1.4% were cognitively impaired, and 10.0% were frail; frailty and cognitive impairment co-occurrence was greater among those with CKD versus those without (1.2%vs.0.1%). Frailty was associated with worse global cognitive function (Cohen's d = -0.26SD,95%CI -0.36,-0.17), and worse cognitive function across all domains; these associations did not differ by CKD (pinteractions > 0.05). Mortality risk prediction improved only among those with CKD when accounting for frailty (p[likelihood ratio test] < 0.001) but not cognitive impairment. CONCLUSIONS: Frailty is associated with worse cognitive function regardless of CKD status. While CKD and frailty improved mortality prediction, cognitive impairment did not. Risk prediction tools should incorporate frailty to improve mortality prediction among those with CKD.