Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 43
Filtrar
1.
Transplantation ; 108(3): 607-608, 2024 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-37677947
3.
Transplant Proc ; 55(1): 56-65, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36623960

RESUMEN

BACKGROUND: To evaluate the effect of the Affordable Care Act (ACA) Medicaid expansion on payor mix among patients on the kidney and liver transplant waiting list as well as waiting list and post-transplant outcomes. DESIGN: Using the Scientific Registry of Transplant Recipients, we performed a secondary data analysis of all patients on the kidney and liver transplant waiting list from 2007 to 2018. We described changes in payor mix by timing of state Medicaid expansion. We used competing risks models to estimate cause-specific hazard ratios for the effects of insurance and era on death/delisting and transplant. We used a Poisson regression model to estimate the effect of insurance and era on incidence rate ratio of inactivations on the waiting list. We used Cox proportional hazards models to estimate the effect of insurance and era on graft and patient survival. RESULTS: A decade after implementation of the ACA, the prevalence of Medicaid beneficiaries listed for transplant increased by 2.5% (from 7.4% to 9.9%) for kidney and by 2.6% (15.3% to 17.9%) for liver. Expansion states had greater increases than nonexpansion states (kidney 3.8% vs 0.6%, liver 5.3% vs -1.8%). Among wait-listed patients, the magnitude of association of Medicaid insurance vs private insurance with transplant decreased over time for kidney candidates (era 1 subdistribution hazard ratio (SHR), 0.62 [95% CI, 0.60-0.64] vs era 3 SHR, 0.77 [95% CI, 0.74-0.70]) but increased for liver candidates (era 1 SHR, 0.85 [95% CI, 0.83-0.90] vs era 3 SHR 0.79 [95% CI, 0.77-0.82]). Medicaid-insured kidney and liver recipients had greater hazards of graft failure; this did not change over time (kidney: HR, 1.23 [95% CI, 1.06-1.44] liver: HR, 1.05 [95% CI, 0.94-1.17]). CONCLUSIONS: For the millions of patients with chronic kidney and liver diseases, implementation of the ACA has resulted in only modest increases in access to transplant for the publicly insured vs the privately insured.


Asunto(s)
Trasplante de Hígado , Patient Protection and Affordable Care Act , Estados Unidos , Humanos , Medicaid , Sistema de Registros , Riñón
4.
Ann Surg ; 277(2): 350-357, 2023 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-33843792

RESUMEN

OBJECTIVE: To define textbook outcome (TO) for lung transplantation (LTx) using a contemporary cohort from a high-volume institution. SUMMARY BACKGROUND DATA: TO is a standardized, composite quality measure based on multiple postoperative endpoints representing the ideal "textbook" hospitalization. METHODS: Adult patients who underwent LTx at our institution between 2016 and 2019 were included. TO was defined as freedom from intraoperative complication, postoperative reintervention, 30-day intensive care unit or hospital readmission, length of stay >75th percentile of LTx patients, 90 day mortality, 30-day acute rejection, grade 3 primary graft dysfunction at 48 or 72 hours, postoperative extracorporeal membrane oxygenation, tracheostomy within 7 days, inpatient dialysis, reintubation, and extubation >48 hours post-transplant. Recipient, operative, financial characteristics, and post-transplant outcomes were recorded from institutional data and compared between TO and non-TO groups. RESULTS: Of 401 LTx recipients, 97 (24.2%) achieved TO. The most common reason for TO failure was extubation >48 hours post-transplant (N = 119, 39.1%); the least common was mortality (N = 15, 4.9%). Patient and graft survival were improved among patients who achieved versus failed TO (patient survival: log-rank P < 0.01; graft survival: log-rank P < 0.01). Rejection-free and chronic lung allograft dysfunction-free survival were similar between TO and non-TO groups (rejection-free survival: log-rank P = 0.07; chronic lung allograft dysfunction-free survival: log-rank P = 0.3). On average, patients who achieved TO incurred approximately $638,000 less in total inpatient charges compared to those who failed TO. CONCLUSIONS: TO in LTx was associated with favorable post-transplant outcomes and significant cost-savings. TO may offer providers and patients new insight into transplant center quality of care and highlight areas for improvement.


Asunto(s)
Trasplante de Pulmón , Indicadores de Calidad de la Atención de Salud , Adulto , Humanos , Estudios Retrospectivos , Pulmón , Trasplante Homólogo
5.
Pediatr Transplant ; 26(8): e14371, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35938682

RESUMEN

BACKGROUND: Malnutrition, including obesity and undernutrition, among children is increasing in prevalence and is common among children on renal replacement therapy. The effect of malnutrition on the pre-transplant immune system and how the pediatric immune system responds to the insult of both immunosuppression and allotransplantation is unknown. We examined the relationship of nutritional status with post-transplant outcomes and characterized the peripheral immune cell phenotypes of children from the Immune Development of Pediatric Transplant (IMPACT) study. METHODS: Ninety-eight patients from the IMPACT study were classified as having obesity, undernutrition, or normal nutrition-based pre-transplant measurements. Incidence of infectious and alloimmune outcomes at 1-year post-transplantation was compared between nutritional groups using Gray's test and Fine-Gray subdistribution hazards model. Event-free survival was estimated by Kaplan-Meier method and compared between groups. Differences in immune cell subsets between nutritional groups over time were determined using generalized estimating equations accounting for the correlation between repeated measurements. RESULTS: We did not observe that nutritional status was associated with infectious or alloimmune events or event-free survival post-transplant. We demonstrated that children with obesity had distinct T-and B-cell signatures relative to those with undernutrition and normal nutrition, even when controlling for immunosuppression. Children with obesity had a lower frequency of CD8 Tnaive cells 9-month post-transplant (p < .001), a higher frequency of CD4 CD57 + PD1- T cells, and lower frequencies of CD57-PD1+ CD8 and CD57-PD1- CD8 T cells at 12-month transplant (p < .05 for all). CONCLUSIONS: Children with obesity have distinct immunophenotypes that may influence the tailoring of immunosuppression.


Asunto(s)
Trasplante de Riñón , Desnutrición , Humanos , Terapia de Inmunosupresión , Linfocitos T CD8-positivos , Desnutrición/complicaciones , Obesidad
6.
Am J Transplant ; 22(6): 1578-1592, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35322536

RESUMEN

Mitochondria released from injured cells activate endothelial cells (ECs), fostering inflammatory processes, including allograft rejection. The stimulator of interferon genes (STING) senses endogenous mitochondrial DNA, triggering innate immune activation via NF-κB signaling. Here, we show that exogenous mitochondria exposure induces EC STING-NF-κB activation, promoting EC/effector memory T cell adhesion, which is abrogated by NF-κB and STING inhibitors. STING activation in mitochondrion-activated ECs is independent of canonical cGMP-AMP synthetase sensing/signaling, but rather is mediated by interferon gamma-inducible factor 16 (IFI16) and can be inhibited by IFI16 inhibition. Internalized mitochondria undergo mitofusion and STING-dependent mitophagy, leading to selective sequestration of internalized mitochondria. The exposure of donor hearts to exogenous mitochondria activates murine heart ECs in vivo. Collectively, our results suggest that IFI16-STING-NF-κB signaling regulates exogenous mitochondrion-induced EC activation and mitophagy, and exogenous mitochondria foster T cell-mediated CoBRR. These data suggest a novel, donor-directed, therapeutic approach toward mitigating perioperative allograft immunogenicity.


Asunto(s)
Trasplante de Corazón , FN-kappa B , Animales , Células Endoteliales/metabolismo , Trasplante de Corazón/efectos adversos , Humanos , Ratones , Mitocondrias/metabolismo , FN-kappa B/metabolismo , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fosfoproteínas , Donantes de Tejidos
7.
Clin Transplant ; 36(5): e14619, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35175664

RESUMEN

There are no established regulations governing patient selection for simultaneous heart-kidney (SHK) transplantation, creating the potential for significant center-level variations in clinical practice. METHODS: Using the United Network for Organ Sharing (UNOS) Standard Transplant Analysis and Research (STAR) file, we examined practice trends and variations in patient selection for SHK at the center level between January 1, 2004 and March 31, 2019. RESULTS: Overall, SHK is becoming more common with most centers performing heart transplants also performing SHK. Among patients who underwent heart transplant who were receiving dialysis, the rate of SHK varied from 22% to 86% at the center level. Among patients not on dialysis, the median estimated glomerular filtration rate (eGFR) of patients receiving SHK varied between 19 and 59 mL/min/1.73 m2 . When adjusting for other factors, the odds of SHK varied 57-fold between the highest and lowest SHK performing centers. CONCLUSION: Variation in SHK at the center level suggests the need for national guidelines around the selection of patients for SHK.


Asunto(s)
Trasplante de Corazón , Trasplante de Riñón , Tasa de Filtración Glomerular , Humanos , Riñón , Selección de Paciente
8.
J Immunol ; 208(3): 762-771, 2022 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-34987112

RESUMEN

Recent advancements in microfluidics and high-throughput sequencing technologies have enabled recovery of paired H and L chains of Igs and VDJ and VJ chains of TCRs from thousands of single cells simultaneously in humans and mice. Despite rhesus macaques being one of the most well-studied model organisms for the human adaptive immune response, high-throughput single-cell immune repertoire sequencing assays are not yet available due to the complexity of these polyclonal receptors. We used custom primers that capture all known rhesus macaque Ig and TCR isotypes and chains that are fully compatible with a commercial solution for single-cell immune repertoire profiling. Using these rhesus-specific assays, we sequenced Ig and TCR repertoires in >60,000 cells from cryopreserved rhesus PBMCs, splenocytes, and FACS-sorted B and T cells. We were able to recover every Ig isotype and TCR chain, measure clonal expansion in proliferating T cells, and pair Ig and TCR repertoires with gene expression profiles of the same single cells. Our results establish the ability to perform high-throughput immune repertoire analysis in rhesus macaques at the single-cell level.


Asunto(s)
Inmunoglobulinas/genética , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Exones VDJ/genética , Animales , Perfilación de la Expresión Génica , Secuenciación de Nucleótidos de Alto Rendimiento , Macaca mulatta , Análisis de la Célula Individual , Linfocitos T/inmunología , Transcriptoma/genética
9.
Kidney360 ; 3(12): 2116-2130, 2022 12 29.
Artículo en Inglés | MEDLINE | ID: mdl-36591367

RESUMEN

Preexisting donor-specific antibodies (DSA) to MHC antigens increase the risk of antibody-mediated rejection (AMR) in sensitized transplant recipients and reduces graft survival. Pretransplant desensitization with costimulation blockade and proteasome inhibition has facilitated transplantation in our preclinical nonhuman primate (NHP) model. However, long-term graft survival is limited by rebound of DSA after transplantation. In this study, we performed kidney transplants between highly sensitized, maximally MHC-mismatched NHPs (n=14). At kidney transplantation, primates received T cell depletion with rhesus-specific anti-thymocyte globulin (rhATG; n=10) or monoclonal anti-CD4 and anti-CD8 antibodies (n=4). Maintenance immunosuppression consisted of belatacept and tacrolimus (n=5) or belatacept and rapamycin (n=9) with steroids. Rebound of DSA post-kidney transplantation was significantly reduced compared with maintenance immunosuppression with tacrolimus, mycophenolate, and steroids. Protocol lymph node biopsy specimens showed a decrease in germinal center activity, with low frequencies of T follicular helper cells and class-switched B cells after kidney transplantation. Combined belatacept and rapamycin was superior in controlling viral reactivation, enabling weaning of ganciclovir prophylaxis. Tacrolimus was associated with increased morbidity that included cytomegalovirus and parvovirus viremia and post-transplant lymphoproliferative disorder. All primates in the tacrolimus/belatacept group failed discontinuation of antiviral therapy. Overall, belatacept-based immunosuppression increased AMR-free graft survival by controlling post-transplant humoral responses in highly sensitized NHP recipients and should be further investigated in a human clinical trial.


Asunto(s)
Inmunidad Humoral , Tacrolimus , Animales , Abatacept/farmacología , Abatacept/uso terapéutico , Anticuerpos , Terapia de Inmunosupresión , Sirolimus/farmacología , Sirolimus/uso terapéutico , Tacrolimus/farmacología , Tacrolimus/uso terapéutico
10.
J Clin Med ; 10(23)2021 Nov 24.
Artículo en Inglés | MEDLINE | ID: mdl-34884207

RESUMEN

The impact of HLA matching on graft survival has been well characterized in renal transplantation, with a higher degree of matching associated with superior graft survival. Additionally, living donor grafts are known to confer superior survival compared to those from deceased donors. The purpose of this study is to report our multi-decade institutional experience and outcomes for patients who received HLA-identical living donor grafts, which represent the most favorable scenario in kidney transplantation. We conducted a retrospective analysis of these graft recipients performed at a Duke University Medical Center between the years of 1965 and 2002. The recipients demonstrated excellent graft and patient survival outcomes, superior to a contemporary cohort, with median patient and graft survival of 24.2 and 30.9 years, respectively, among Duke recipients vs. 16.1 and 16.0 years in a cohort derived from national data. This study offers a broad perspective on the importance of HLA matching and graft type, and demonstrates a historical best-case-scenario in renal transplantation.

11.
Front Immunol ; 12: 714723, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34526991

RESUMEN

Donor specific transfusions have been the basis of tolerance inducing protocols since Peter Medawar showed that it was experimentally feasible in the 1950s. Though trials of cellular therapies have become increasingly common in solid organ transplantation, they have not become standard practice. Additionally, whereas some protocols have focused on cellular therapies as a method for donor antigen delivery-thought to promote tolerance in and of itself in the correct immunologic context-other approaches have alternatively focused on the intrinsic immunosuppressive properties of the certain cell types with less emphasis on their origin, including mesenchymal stem cells, regulatory T cells, and regulatory dendritic cells. Regardless of intent, all cellular therapies must contend with the potential that introducing donor antigen in a new context will lead to sensitization. In this review, we focus on the variety of cellular therapies that have been applied in human trials and non-human primate models, describe their efficacy, highlight data regarding their potential for sensitization, and discuss opportunities for cellular therapies within our current understanding of the immune landscape.


Asunto(s)
Tratamiento Basado en Trasplante de Células y Tejidos , Trasplante de Órganos , Animales , Tratamiento Basado en Trasplante de Células y Tejidos/efectos adversos , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Tratamiento Basado en Trasplante de Células y Tejidos/tendencias , Terapia Combinada , Rechazo de Injerto/inmunología , Supervivencia de Injerto/inmunología , Trasplante de Células Madre Hematopoyéticas , Humanos , Tolerancia Inmunológica , Terapia de Inmunosupresión , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Trasplante de Órganos/efectos adversos , Trasplante de Órganos/métodos , Trasplante de Órganos/tendencias , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Donantes de Tejidos , Trasplante Homólogo
12.
Hepatol Commun ; 5(9): 1527-1542, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34510831

RESUMEN

Normothermic machine perfusion (NMP) provides clinicians an opportunity to assess marginal livers before transplantation. However, objective criteria and point-of-care (POC) biomarkers to predict risk and guide decision making are lacking. In this investigation, we characterized trends in POC biomarkers during NMP and compared primate donation after circulatory death (DCD) livers with short and prolonged warm ischemic injury. Following asystole, livers were subjected to either 5 minutes (DCD-5min, n = 4) or 45 minutes (DCD-45min, n = 4) of warm ischemia time. Livers were flushed with heparinized UW solution, and preserved in cold storage before NMP. During flow-controlled NMP, circulating perfusate and tissue biopsies were collected at 0, 2, 4, 6, and 8 hours for analysis. DCD-45min livers had greater terminal portal vein pressure (8.5 vs. 13.3 mm Hg, P = 0.027) and terminal portal vein resistance (16.3 vs. 32.4 Wood units, P = 0.005). During perfusion, DCD-45min livers had equivalent terminal lactate clearance (93% vs. 96%, P = 0.344), greater terminal alanine aminotransferase (163 vs. 883 U/L, P = 0.002), and greater terminal perfusate gamma glutamyltransferase (GGT) (5.0 vs. 31.7 U/L, P = 0.002). DCD-45min livers had higher circulating levels of flavin mononucleotide (FMN) at hours 2 and 4 of perfusion (136 vs. 250 ng/mL, P = 0.029; and 158 vs. 293 ng/mL, P = 0.003; respectively). DCD-5min livers produced more bile and demonstrated progressive decline in bile lactate dehydrogenase, whereas DCD-45min livers did not. On blinded histologic evaluation, DCD-45min livers demonstrated greater injury and necrosis at late stages of perfusion, indicative of nonviability. Conclusion: Objective criteria are needed to define graft viability during NMP. Perfusate lactate clearance does not discriminate between viable and nonviable livers during NMP. Perfusate GGT and FMN may represent POC biomarkers predictive of liver injury during NMP.

13.
Transplant Direct ; 7(10): e748, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34476293

RESUMEN

Recurrent focal segmental glomerulosclerosis (FSGS) after kidney transplantation accounts for the majority of allograft failures in children with primary FSGS. Although current research focuses on FSGS pathophysiology, a common etiology and mechanisms of disease recurrence remain elusive. METHODS: We performed a retrospective review of the Scientific Registry of Transplant Recipients to determine the association of specific HLA recurrence of FSGS. Kidney transplants recipients under the age of 19 who were diagnosed with FSGS, who were transplanted after January 1, 2000, and who had complete HLA data were included in the study. We performed simple logistic regression on all HLA A, B, C, DR, and DQ represented in the dataset and FSGS recurrence and then determined those associated with recurrence using the Benjamini-Hochberg method for multiple comparisons. For those HLAs that were associated with recurrence, we further determined the effect of matching recipient and donor HLA with recurrence. RESULTS: HLA DR7, DR53, DQ2, DR52, and DQ7 were associated with increased or decreased risk of recurrent disease after transplantation. We identified a risk haplotype consisting of HLA-DR7, DR53, and DQ2 that was consistently associated with an increased risk of recurrence (odds ratio 1.91; 95% confidence interval, 1.44-2.54, P < 0.001). We also found that donor/recipient concordance for HLA-DQ7 was associated with a decreased risk of recurrence (odds ratio 0.42; 95% confidence interval, 0.37-0.53, P = 0.009). CONCLUSIONS: HLA profiles may be used for risk stratification of recurrence of FSGS in pediatric kidney transplant recipients and deserves further study.

14.
Transplant Direct ; 7(9): e742, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-34386579

RESUMEN

BACKGROUND: Livers from "nonideal" but acceptable donors are underutilized; however, organ procurement organization (OPO) metrics do not assess how OPO-specific practices contribute to these trends. In this analysis, we evaluated nonideal liver donor avoidance or risk aversion among OPOs and within US donation service areas (DSAs). METHODS: Adult donors in the United Network for Organ Sharing registry who donated ≥1 organ for transplantation between 2007 and 2019 were included. Nonideal donors were defined by any of the following: age > 70, hepatitis C seropositive, body mass index > 40, donation after circulatory death, or history of malignancy. OPO-specific performance was evaluated based on rates of nonideal donor pursuit and consent attainment. DSA performance (OPO + transplant centers) was evaluated based on rates of nonideal donor pursuit, consent attainment, liver recovery, and transplantation. Lower rates were considered to represent increased donor avoidance or increased risk aversion. RESULTS: Of 97 911 donors, 31 799 (32.5%) were nonideal. Unadjusted OPO-level rates of nonideal donor pursuit ranged from 88% to 100%. In a 5-tier system of overall risk aversion, tier 5 DSAs (least risk-averse) and tier 1 DSAs (most risk-averse) had the highest and lowest respective rates of non-ideal donor pursuit, consent attainment, liver recovery, and transplantation. On average, recovery rates were over 25% higher among tier 5 versus tier 1 DSAs. If tier 1 DSAs had achieved the same average liver recovery rate as tier 5 DSAs, approximately 2100 additional livers could have been recovered during the study period. CONCLUSION: Most OPOs aggressively pursue nonideal liver donors; however, recovery practices vary widely among DSAs. Fair OPO evaluations should consider early donation process stages to best disentangle OPO and center-level practices.

15.
Hepatobiliary Surg Nutr ; 10(3): 315-324, 2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34159159

RESUMEN

BACKGROUND: Selection of the optimal treatment modality for primary liver cancers remains complex, balancing patient condition, liver function, and extent of disease. In individuals with preserved liver function, liver resection remains the primary approach for treatment with curative intent but may be associated with significant mortality. The purpose of this study was to establish a simple scoring system based on Model for End-stage Liver Disease (MELD) and extent of resection to guide risk assessment for liver resections. METHODS: The 2005-2015 NSQIP database was queried for patients undergoing liver resection for primary liver malignancy. We first developed a model that incorporated the extent of resection (1 point for major hepatectomy) and a MELD-Na score category of low (MELD-Na =6, 1 point), medium (MELD-Na =7-10, 2 points) or high (MELD-Na >10, 3 points) with a score range of 1-4, called the Hepatic Resection Risk Score (HeRS). We tested the predictive value of this model on the dataset using logistic regression. We next developed an optimal multivariable model using backwards sequential selection of variables under logistic regression. We performed K-fold cross validation on both models. Receiver operating characteristics were plotted and the optimal sensitivity and specificity for each model were calculated to obtain positive and negative predictive values. RESULTS: A total of 4,510 patients were included. HeRS was associated with increased odds of 30-day mortality [HeRS =2: OR =3.23 (1.16-8.99), P=0.025; HeRS =3: OR =6.54 (2.39-17.90), P<0.001; HeRS =4: OR =13.69 (4.90-38.22), P<0.001]. The AUC for this model was 0.66. The AUC for the optimal multivariable model was higher at 0.76. Under K-fold cross validation, the positive predictive value (PPV) and negative predictive value (NPV) of these two models were similar at PPV =6.4% and NPV =97.7% for the HeRS only model and PPV =8.4% and NPV =98.1% for the optimal multivariable model. CONCLUSIONS: The HeRS offers a simple heuristic for estimating 30-day mortality after resection of primary liver malignancy. More complicated models offer better performance but at the expense of being more difficult to integrate into clinical practice.

16.
HPB (Oxford) ; 23(12): 1830-1836, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-33980477

RESUMEN

BACKGROUND: Liver transplantation is definitive therapy for end stage liver disease in pediatric patients. Living donor liver transplantation (LDLT) with the left lateral segment (LLS) is often a feasible option. However, the size of LLS is an important factor in donor suitability - particularly when the recipient weighs less than 10 kg. In the present study, we sought to define a formula for estimating left lateral segment volume (LLSV) in potential LLS donors. METHODS: We obtained demographic and anthropometric measurements on 50 patients with Computed Tomography (CT) scans to determine whole liver volume (WLV), right liver volume (RLV), and LLSV. We performed univariable and multivariable linear regression with backwards stepwise variable selection (p < 0.10) to determine final models. RESULTS: Our study found that previously reported anthropometric and demographics variables correlated with volume were significantly associated with WLV and RLV. On univariable analysis, no demographic or anthropometric measures were correlated with LLSV. On multivariable analysis, LLSV was poorly predicted by the final model (R2 = 0.10, Coefficient of Variation [CV] = 42.2) relative to WLV (R2 = 0.33, CV = 18.8) and RLV (R2 = 0.41, CV = 15.8). CONCLUSION: Potential LLS living donors should not be excluded based on anthropometric data: all potential donors should be evaluated regardless of their size.


Asunto(s)
Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Niño , Humanos , Hígado/diagnóstico por imagen , Hígado/cirugía , Trasplante de Hígado/efectos adversos , Donadores Vivos
17.
Clin Transplant ; 35(8): e14369, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34021521

RESUMEN

Rabbit antithymocyte globulin (RATG) preparations are widely used in transplantation. They are developed in vivo against thymocytes and contain polyclonal antibodies specific for myriad cellular targets. The rhesus monkey is commonly used as a preclinical transplant model, but the fidelity of commercially available human-specific RATGs to anticipate the effects of RATGs in rhesus has not been established. We therefore developed two rhesus-specific ATGs (rhATG) and compared them to human-specific RATG (huATG, Thymoglobulin® ) in rhesus monkeys, assessing the magnitude and phenotype of depletion peripherally and in lymph nodes. Four primates were assigned to each group and received 20 mg/kg of drug. Depletion, repopulation, and changes in lymphocyte subsets were evaluated in peripheral blood and lymph nodes by flow cytometry over four months. We observed similar qualitative changes in lymphocyte subsets, but a generally more profound depletion with huATG compared to either rhATG. Peripheral homeostatic proliferation rather than thymic output was the major mechanism for repopulation with all RATGs. Repopulation was slower but qualitatively similar when examining RATGs in additional animals receiving concomitant chronic immunosuppression. Depletional induction is similar to human- and rhesus-specific RATGs in rhesus macaques. Both rhesus- and human-specific agents appear appropriate for preclinical modeling of clinical RATG use.


Asunto(s)
Suero Antilinfocítico , Animales , Citometría de Flujo , Humanos , Macaca mulatta
18.
Am J Transplant ; 21(9): 3163-3174, 2021 09.
Artículo en Inglés | MEDLINE | ID: mdl-33942491

RESUMEN

Thymic output and homeostatic mature cell proliferation both influence T cell repopulation following depletional induction, though the relative contribution of each and their association with recipient age have not been well studied. We investigated the repopulating T cell kinetics in kidney transplant recipients who underwent alemtuzumab induction followed by belatacept/rapamycin-based immunosuppression over 36-month posttransplantation. We focused specifically on the correlation between repopulating T cell subsets and the age of patients. Substantial homeostatic Ki67-expressing T cell proliferation was seen posttransplantation. A repertoire enriched for naïve T (TNaïve ) cells emerged posttransplantation. Analysis by generalized estimating equation linear models revealed a strong negative linear association between reconstituting TNaïve cells and advancing age. A relationship between age and persistence of effector memory cells was shown. We assessed thymic output and found an increase in the frequency of recent thymic emigrants (RTEs, CD4+ CD31+ ) at 12-month posttransplantation. Patients under 30 years of age showed significantly higher levels of CD4+ CD31+ cells than patients over 55 years of age pre- and posttransplantation. IL-7 and autologous mature dendritic cells (mDCs) induced CD57- cell proliferation. In contrast, mDCs, but not IL-7, induced CD57+ cell proliferation. This study establishes the relationship between age and thymic output during T cell homeostatic repopulation after alemtuzumab induction. Trial Registration: ClinicalTrials.gov - NCT00565773.


Asunto(s)
Trasplante de Riñón , Abatacept , Proliferación Celular , Humanos , Terapia de Inmunosupresión , Persona de Mediana Edad , Receptores de Trasplantes
19.
Liver Transpl ; 27(8): 1106-1115, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-33733560

RESUMEN

Historically in the United States, kidneys for simultaneous liver-kidney transplantation (SLKT) candidates were allocated with livers, prioritizing SLKT recipients over much of the kidney waiting list. A 2017 change in policy delineated renal function criteria for SLKT and implemented a safety net for kidney-after-liver transplantation. We compared the use and outcomes of SLKT and kidney-after-liver transplant with the 2017 policy. United Network for Organ Sharing Standard Transplant Analysis and Research files were used to identify adults who received liver transplantations (LT) from August 10, 2007 to August 10, 2012; from August 11, 2012 to August 10, 2017; and from August 11, 2017 to June 12, 2019. LT recipients with end-stage renal disease (ESRD) were defined by dialysis requirement or estimated glomerular filtration rate <25. We evaluated outcomes and center-level, regional, and national practice before and after the policy change. Nonparametric cumulative incidence of kidney-after-liver listing and transplant were modeled by era. A total of 6332 patients received SLKTs during the study period; fewer patients with glomerular filtration rate (GFR) ≥50 mL/min underwent SLKT over time (5.8%, 4.8%, 3.0%; P = 0.01 ). There was also less variability in GFR at transplant after policy implementation on center and regional levels. We then evaluated LT-alone (LTA) recipients with ESRD (n = 5408 from 2012-2017; n = 2321 after the policy). Listing for a kidney within a year of LT increased from 2.9% before the policy change to 8.8% after the policy change, and the rate of kidney transplantation within 1 year increased from 0.7% to 4% (P < 0.001). After the policy change, there was no difference in patient survival rates between SLKT and LTA among patients with ESRD. Implementation of the 2017 SLKT policy change resulted in reduced variability in SLKT recipient kidney function and increased access to deceased donor kidney transplantation for LTA recipients with kidney disease without negatively affecting outcomes.


Asunto(s)
Trasplante de Hígado , Adulto , Humanos , Riñón/fisiología , Riñón/cirugía , Hígado , Políticas , Diálisis Renal , Estudios Retrospectivos , Estados Unidos/epidemiología
20.
Nephrol Ther ; 17(4): 245-251, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33541842

RESUMEN

BACKGROUND: The first wave of the Covid-19 pandemic resulted in a drastic reduction in kidney transplantation and a profound change in transplant care in France. It is critical for kidney transplant centers to understand the behaviors, concerns and wishes of transplant recipients and waiting list candidates. METHODS: French kidney patients were contacted to answer an online electronic survey at the end of the lockdown. RESULTS: At the end of the first wave of the pandemic in France (11 May 2020), 2112 kidney transplant recipients and 487 candidates answered the survey. More candidates than recipients left their home during the lockdown, mainly for health care (80.1% vs. 69.4%; P<0.001). More candidates than recipients reported being exposed to Covid-19 patients (2.7% vs. 1.2%; P=0.006). Many recipients and even more candidates felt inadequately informed by their transplant center during the pandemic (19.6% vs. 54%; P<0.001). Among candidates, 71.1% preferred to undergo transplant as soon as possible, 19.5% preferred to wait until Covid-19 had left their community, and 9.4% were not sure what to do. CONCLUSIONS: During the Covid-19 pandemic in France, the majority of candidates wished to receive a transplant as soon as possible without waiting until Covid-19 had left their community. Communication between kidney transplant centers and patients must be improved to better understand and serve patients' needs.


Asunto(s)
Actitud Frente a la Salud , COVID-19 , Trasplante de Riñón , Prioridad del Paciente , Listas de Espera , Estudios de Cohortes , Control de Enfermedades Transmisibles , Comunicación , Femenino , Francia , Humanos , Masculino , Persona de Mediana Edad , Pandemias , Encuestas y Cuestionarios
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...