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1.
N Engl J Med ; 391(15): 1390-1401, 2024 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-39413376

RESUMO

BACKGROUND: Kidney transplantation from donors with human immunodeficiency virus (HIV) to recipients with HIV is an emerging practice. It has been performed since 2016 under the U.S. congressional HIV Organ Policy Equity Act and is currently approved for research only. The Department of Health and Human Services is considering expanding the procedure to clinical practice, but data are limited to small case series that did not include donors without HIV as controls. METHODS: In an observational study conducted at 26 U.S. centers, we compared transplantation of kidneys from deceased donors with HIV and donors without HIV to recipients with HIV. The primary outcome was a safety event (a composite of death from any cause, graft loss, serious adverse event, HIV breakthrough infection, persistent failure of HIV treatment, or opportunistic infection), assessed for noninferiority (margin for the upper bound of the 95% confidence interval, 3.00). Secondary outcomes included overall survival, survival without graft loss, rejection, infection, cancer, and HIV superinfection. RESULTS: We enrolled 408 transplantation candidates, of whom 198 received a kidney from a deceased donor; 99 received a kidney from a donor with HIV and 99 from a donor without HIV. The adjusted hazard ratio for the composite primary outcome was 1.00 (95% confidence interval [CI], 0.73 to 1.38), which showed noninferiority. The following secondary outcomes were similar whether the donor had HIV or not: overall survival at 1 year (94% vs. 95%) and 3 years (85% vs. 87%), survival without graft loss at 1 year (93% vs. 90%) and 3 years (84% vs. 81%), and rejection at 1 year (13% vs. 21%) and 3 years (21% vs. 24%). The incidence of serious adverse events, infections, surgical or vascular complications, and cancer was similar in the groups. The incidence of HIV breakthrough infection was higher among recipients of kidneys from donors with HIV (incidence rate ratio, 3.14; 95%, CI, 1.02 to 9.63), with one potential HIV superinfection among the 58 recipients in this group with sequence data and no persistent failures of HIV treatment. CONCLUSIONS: In this observational study of kidney transplantation in persons with HIV, transplantation from donors with HIV appeared to be noninferior to that from donors without HIV. (Funded by the National Institute of Allergy and Infectious Diseases; ClinicalTrials.gov number, NCT03500315.).


Assuntos
Infecções Irruptivas , Infecções por HIV , Falência Renal Crônica , Transplante de Rim , Doadores de Tecidos , Obtenção de Tecidos e Órgãos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções Irruptivas/epidemiologia , Infecções Irruptivas/imunologia , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/imunologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Obtenção de Tecidos e Órgãos/métodos , Falência Renal Crônica/complicações , Falência Renal Crônica/mortalidade , Falência Renal Crônica/terapia
2.
Int J Cancer ; 154(12): 2043-2053, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38345158

RESUMO

We assessed whether contemporary immunosuppression agents were associated with cancer among kidney transplant recipients (KTR), and if this association varied by age and sex. We studied a retrospective province-wide cohort of primary KTR (1997-2016). Employing multivariable Cox models, we estimated associations of cumulative doses of prednisone, mycophenolate and tacrolimus administered over the past 10 years, lagged by 2 years, with the incidence of primary malignant neoplasms (PMN). We assessed interactions with age and sex. To assess the impact of exposure recency, we used weighted cumulative exposure (WCE) modeling. Among 1064 KTR, 108 (10.2%) developed PMN over median follow-up of 73 months (interquartile range: 32-120). Adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) of 0.96 (0.64-1.43), 1.34 (0.96-1.86), and 1.06 (0.88-1.29) were estimated for cumulative daily doses of prednisone (5 mg), mycophenolate (1000 mg), and tacrolimus (2 mg) administered continuously over the past 10 years, respectively. PMN risk associated with cumulative tacrolimus exposure was modified by age (interaction p = .035) and was more pronounced in 15-year and 30-year-old KTR (aHRs of 1.57 [1.08-2.28] and 1.31 [1.03-1.66], respectively) in comparison to older KTR. PMN risk increase associated with higher cumulative mycophenolate dose was more pronounced in females (aHR = 1.86 [1.15-3.00]) than in males (aHR = 1.16 [0.74-1.81]; interaction p = .131). WCE analyses suggested increased PMN risk the higher the mycophenolate doses taken 5-10 years ago. A trend toward increased PMN risk with long-term mycophenolate exposure, particularly in females, and more pronounced risk with long-term tacrolimus exposure in younger KTR, identify opportunities for tailored immunosuppression to mitigate cancer risk.


Assuntos
Transplante de Rim , Neoplasias , Masculino , Feminino , Humanos , Adolescente , Tacrolimo/efeitos adversos , Estudos Retrospectivos , Prednisona/efeitos adversos , Transplante de Rim/efeitos adversos , Ácido Micofenólico/efeitos adversos , Rejeição de Enxerto/epidemiologia , Imunossupressores/efeitos adversos , Terapia de Imunossupressão/efeitos adversos , Inibidores Enzimáticos , Neoplasias/induzido quimicamente , Neoplasias/epidemiologia , Transplantados
3.
Am J Transplant ; 24(10): 1828-1836, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38636806

RESUMO

Administrative claims data could provide a unique opportunity to identify acute rejection (AR) events using specific antirejection medications and to validate rejected data reported to the Organ Procurement and Transplantation Network. This retrospective cohort study examined differences in registry-reported events and those identified using claims data among adult kidney transplant recipients from 2012 to 2017 using Standard Analysis Files from the US Renal Data System. Rejection rates, survival estimates, and center-level differences were assessed using each approach. Among 45 880 first-time kidney transplant recipients, we identified 3841 AR events within 12 months of transplant reported by centers in the registry; claims data yielded 2945 events. Of all events occurring within 12 months of transplant, 48.5% were reported using registry only, 32.9% were identified using claims only, and 18.6% were identified using both approaches. A 3-year death-censored graft survival probability was 90.0%, 88.4%, and 81.2% (P < .001) for ARs identified using registry only, claims data only, and both approaches, respectively. The large discordance between registry-reported and claims-based events suggests incomplete and potentially inaccurate reporting of events in the Organ Procurement Transplant Network registry. These findings have important implications for analyses that use AR data and underscore the need for improved capture of clinically meaningful events.


Assuntos
Rejeição de Enxerto , Sobrevivência de Enxerto , Transplante de Rim , Sistema de Registros , Humanos , Transplante de Rim/mortalidade , Sistema de Registros/estatística & dados numéricos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Seguimentos , Prognóstico , Falência Renal Crônica/cirurgia , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Obtenção de Tecidos e Órgãos/normas , Fatores de Risco , Taxa de Sobrevida , Taxa de Filtração Glomerular , Estados Unidos/epidemiologia , Testes de Função Renal
4.
Am J Transplant ; 24(7): 1267-1278, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38431077

RESUMO

Pediatric heart failure and transplantation carry associated risks for kidney failure and potential need for kidney transplant following pediatric heart transplantation (KT/pHT). This retrospective, United Network of Organ Sharing study of 10,030 pediatric heart transplants (pHTs) from 1987 to 2020 aimed to determine the incidence of waitlisting for and completion of KT/pHT, risk factors for KT/pHT, and risk factors for nonreceipt of a KT/pHT. Among pHT recipients, 3.4% were waitlisted for KT/pHT (median time of 14 years after pHT). Among those waitlisted, 70% received a KT/pHT, and 18% died on the waitlist at a median time of 0.8 years from KT/pHT waitlisting (median age of 20 years). Moderate-high sensitization at KT/pHT waitlisting (calculated panel reactive antibody, ≥ 20%) was associated with a lower likelihood of KT/pHT (adjusted hazard ratio, 0.67; 95% confidence interval, 0.47-0.95). Waitlisting for heart transplantation simultaneously with kidney transplant (adjusted hazard ratio, 3.73; 95% confidence interval, 2.01-6.92) was associated with increased risk of death on the KT/pHT waitlist. While the prevalence of KT/pHT is low, there is substantial mortality among those waitlisted for KT/pHT. These findings suggest a need to consider novel risk factors for nonreceipt of KT/pHT and death on the waitlist in prioritizing criteria/guidelines for simultaneous heart-kidney transplantation.


Assuntos
Insuficiência Cardíaca , Transplante de Coração , Transplante de Rim , Listas de Espera , Humanos , Transplante de Coração/efeitos adversos , Transplante de Coração/mortalidade , Masculino , Transplante de Rim/efeitos adversos , Feminino , Fatores de Risco , Estudos Retrospectivos , Criança , Prevalência , Adolescente , Pré-Escolar , Adulto Jovem , Seguimentos , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/epidemiologia , Prognóstico , Adulto , Sobrevivência de Enxerto , Lactente , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Obtenção de Tecidos e Órgãos , Taxa de Filtração Glomerular
5.
J Hepatol ; 80(1): 99-108, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37722533

RESUMO

BACKGROUND & AIMS: There is controversy regarding the optimal calcineurin inhibitor type after liver transplant(ation) (LT) for primary sclerosing cholangitis (PSC). We compared tacrolimus with cyclosporine in a propensity score-matched intention-to-treat analysis based on registries representing nearly all LTs in Europe and the US. METHODS: From the European Liver Transplant Registry (ELTR) and Scientific Registry of Transplant Recipients (SRTR), we included adult patients with PSC undergoing a primary LT between 2000-2020. Patients initially treated with cyclosporine were propensity score-matched 1:3 with those initially treated with tacrolimus. The primary outcomes were patient and graft survival rates. RESULTS: The propensity score-matched sample comprised 399 cyclosporine-treated and 1,197 tacrolimus-treated patients with PSC. During a median follow-up of 7.4 years (IQR 2.3-12.8, 12,579.2 person-years), there were 480 deaths and 231 re-LTs. The initial tacrolimus treatment was superior to cyclosporine in terms of patient and graft survival, with 10-year patient survival estimates of 72.8% for tacrolimus and 65.2% for cyclosporine (p <0.001) and 10-year graft survival estimates of 62.4% and 53.8% (p <0.001), respectively. These findings were consistent in the subgroups according to age, sex, registry (ELTR vs. SRTR), time period of LT, MELD score, and diabetes status. The acute rejection rates were similar between groups. In the multivariable Cox regression analysis, tacrolimus (hazard ratio 0.72, p <0.001) and mycophenolate use (hazard ratio 0.82, p = 0.03) were associated with a reduced risk of graft loss or death, whereas steroid use was not significant. CONCLUSIONS: Tacrolimus is associated with better patient and graft survival rates than cyclosporine and should be the standard calcineurin inhibitor used after LT for patients with PSC. IMPACT AND IMPLICATIONS: The optimal calcineurin inhibitor to use after liver transplantation in patients with primary sclerosing cholangitis has yet to be firmly established. Since randomized trials with long follow-up are unlikely to be performed, multicontinental long-term registry data are essential in informing clinical practices. Our study supports the practice of using tacrolimus instead of cyclosporine in the initial immunosuppressive regimen after liver transplantation for patients with primary sclerosing cholangitis. The retrospective registry-based design is a limitation.


Assuntos
Colangite Esclerosante , Transplante de Fígado , Adulto , Humanos , Tacrolimo/uso terapêutico , Ciclosporina/uso terapêutico , Inibidores de Calcineurina , Estudos Retrospectivos , Transplante de Fígado/efeitos adversos , Colangite Esclerosante/tratamento farmacológico , Colangite Esclerosante/cirurgia , Colangite Esclerosante/etiologia , Análise de Intenção de Tratamento , Pontuação de Propensão , Imunossupressores/uso terapêutico , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/tratamento farmacológico , Sobrevivência de Enxerto
6.
Liver Transpl ; 30(1): 61-71, 2024 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-37439661

RESUMO

Avoidance of steroids in pediatric liver transplantation may reduce toxicity and morbidity. The aim of this study was to analyze the feasibility of a steroid-free tacrolimus-basiliximab immunosuppression scheme, the risk factors associated with steroid requirement, and safety parameters. Patients who underwent liver transplantation for biliary atresia between 2011 and 2019 were included and followed for 6 months after transplantation. Immunosuppression consisted of tacrolimus-based treatment with basiliximab induction. Steroid-free survival was estimated, and risk factors for steroid requirement were evaluated using multivariate Cox regression analysis. A total of 76 patients were included, of whom 42 (55.3%) required steroids (>14 d) due to biopsy-proven acute rejection (47.6%, n = 20), instability in liver function tests (35.7%, n = 15), tacrolimus-related adverse drug reactions (14.3%, n = 6), or other reasons (bronchospasm episode, n = 1). Steroid-free survival was 45.9% (95% CI, 35.9-58.8). Independent factors associated with steroid requirement included tortuosity in tacrolimus trough levels (≥1.76 vs. <1.76: HR 5.8, 95% CI, 2.6-12.7; p < 0.001) and mean tacrolimus trough levels (≥ 6.4 ng/mL vs. < 6.4 ng/mL: HR 0.4, 95% CI, 0.2-0.7; p = 0.002). The rate of bacterial and viral infections was comparable between patients with and without steroids, although in the former group, cytomegalovirus infection developed earlier ( p = 0.03). Patients receiving steroids had higher total cholesterol, LDL, and HDL levels ( p < 0.05) during follow-up, but no changes in the height Z-score were observed 1 year after transplantation. Basiliximab induction in combination with tacrolimus-based treatment avoided steroid requirements in 45% of the patients. Tacrolimus variability and trough levels below 6.4 ng/mL independently increased the risk of steroid requirement. Further efforts should be focused on personalizing immunosuppressive treatment.


Assuntos
Transplante de Fígado , Tacrolimo , Humanos , Criança , Basiliximab/efeitos adversos , Tacrolimo/efeitos adversos , Transplante de Fígado/efeitos adversos , Anticorpos Monoclonais/efeitos adversos , Estudos de Viabilidade , Imunossupressores/efeitos adversos , Terapia de Imunossupressão/efeitos adversos , Esteroides/efeitos adversos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/tratamento farmacológico
7.
Liver Transpl ; 30(10): 1039-1049, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38647419

RESUMO

Acute allograft rejection is a well-known complication of liver transplantation (LT). The incidence, epidemiology, and outcomes of acute rejection have not been well described in Australia. We retrospectively studied consecutive adults who underwent deceased donor LT at a single center between 2010 and 2020. Donor and recipient data at the time of LT and recipient outcomes were collected from a prospective LT database. Liver biopsy reports were reviewed, and only a graft's first instance of biopsy-proven acute rejection was analyzed. During the study period, 796 liver transplants were performed in 770 patients. Biopsy-proven rejection occurred in 34.9% of transplants. There were no significant changes in the incidence of rejection over time (linear trend p =0.11). The median time to the first episode of rejection was 71 days after LT: 2.2% hyperacute, 50.4% early (≤90 d), and 47.5% late rejection (>90 d). Independent risk factors for rejection were younger recipient age at transplant (aHR 0.98 per year increase, 95% CI: 0.97-1.00, p =0.01), and ABO-incompatible grafts (aHR 2.55 vs. ABO-compatible, 95% CI: 1.27-5.09, p <0.01) while simultaneous multiorgan transplants were protective (aHR 0.21 vs. LT only, 95% CI: 0.08-0.58, p <0.01). Development of acute rejection (both early and late) was independently associated with significantly reduced graft (aHR 3.13, 95% CI: 2.21-4.42, p <0.001) and patient survival (aHR 3.42, 95% CI: 2.35-4.98, p <0.001). In this 11-year Australian study, acute LT rejection occurred in 35%, with independent risk factors of younger recipient age and ABO-incompatible transplant, while having a simultaneous multiorgan transplant was protective. Acute rejection was independently associated with reduced graft and patient survival after adjustment for other factors.


Assuntos
Rejeição de Enxerto , Sobrevivência de Enxerto , Transplante de Fígado , Humanos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Transplante de Fígado/efeitos adversos , Transplante de Fígado/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Feminino , Incidência , Estudos Retrospectivos , Austrália/epidemiologia , Fatores de Risco , Adulto , Doença Aguda , Biópsia , Fatores Etários , Idoso , Fígado/patologia , Fígado/imunologia , Fígado/cirurgia , Resultado do Tratamento , Aloenxertos/patologia , Aloenxertos/imunologia , Fatores de Tempo , Doença Hepática Terminal/cirurgia , Doença Hepática Terminal/mortalidade
8.
Liver Transpl ; 30(9): 887-895, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38727618

RESUMO

There is no recent update on the clinical course of retransplantation (re-LT) after living donor liver transplantation (LDLT) in the US using recent national data. The UNOS database (2002-2023) was used to explore patient characteristics in initial LT, comparing deceased donor liver transplantation (DDLT) and LDLT for graft survival (GS), reasons for graft failure, and GS after re-LT. It assesses waitlist dropout and re-LT likelihood, categorizing re-LT cohort based on time to re-listing as acute or chronic (≤ or > 1 mo). Of 132,323 DDLT and 5955 LDLT initial transplants, 3848 DDLT and 302 LDLT recipients underwent re-LT. Of the 302 re-LT following LDLT, 156 were acute and 146 chronic. Primary nonfunction (PNF) was more common in DDLT, although the difference was not statistically significant (17.4% vs. 14.8% for LDLT; p = 0.52). Vascular complications were significantly higher in LDLT (12.5% vs. 8.3% for DDLT; p < 0.01). Acute re-LT showed a larger difference in primary nonfunction between DDLT and LDLT (49.7% vs. 32.0%; p < 0.01). Status 1 patients were more common in DDLT (51.3% vs. 34.0% in LDLT; p < 0.01). In the acute cohort, Kaplan-Meier curves indicated superior GS after re-LT for initial LDLT recipients in both short-term and long-term ( p = 0.02 and < 0.01, respectively), with no significant difference in the chronic cohort. No significant differences in waitlist dropout were observed, but the initial LDLT group had a higher re-LT likelihood in the acute cohort (sHR 1.40, p < 0.01). A sensitivity analysis focusing on the most recent 10-year cohort revealed trends consistent with the overall study findings. LDLT recipients had better GS in re-LT than DDLT. Despite a higher severity of illness, the DDLT cohort was less likely to undergo re-LT.


Assuntos
Bases de Dados Factuais , Sobrevivência de Enxerto , Transplante de Fígado , Doadores Vivos , Reoperação , Listas de Espera , Humanos , Transplante de Fígado/estatística & dados numéricos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Doadores Vivos/estatística & dados numéricos , Feminino , Masculino , Estados Unidos/epidemiologia , Reoperação/estatística & dados numéricos , Pessoa de Meia-Idade , Adulto , Bases de Dados Factuais/estatística & dados numéricos , Listas de Espera/mortalidade , Resultado do Tratamento , Fatores de Tempo , Idoso , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Fatores de Risco
9.
J Pediatr ; 264: 113744, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37726087

RESUMO

OBJECTIVE: To compare long-term outcomes of pediatric liver transplant (LT) recipients off immunosuppression (IS) with matched controls on IS using data from the Society of Pediatric Liver Transplant (SPLIT) registry. STUDY DESIGN: This was a retrospective case-control study. SPLIT participants <18 years of age, ≥4 years after isolated LT, and off IS for ≥1 year (cases) were age- and sex-matched 1:2 to patients with the same primary diagnosis and post-LT follow-up duration (controls). Primary outcomes included retransplantation, allograft rejection, IS comorbidities, and prevalence of SPLIT-derived composite ideal outcome (c-IO) achieved at the end of the follow-up period. Differences were compared using multiple linear regression for continuous outcomes and logistic regression for dichotomous data. RESULTS: The study cohort was composed of 33 cases (42.4% male, 60.6% biliary atresia, median age at LT of 0.7 [P25, P75, 0.5, 1.6] years, median IS withdrawal time of 9 [P25, P75, 6, 12] years after LT) and 66 age- and sex-matched controls. No cases required retransplantation. Cases and controls had similar growth parameters, laboratory values, calculated glomerular filtration rates, rates of post-transplant lymphoproliferative disease, graft rejection, and attainment of c-IO. CONCLUSIONS: No differences in allograft rejection rates, IS complications, or c-IO prevalence were seen between SPLIT patients off IS and age- and sex-matched controls remaining on IS. Discontinuation of IS most commonly occurred in the context of rigorously designed IS withdrawal trials. The available sample size was small, affecting generalizability to the broader pediatric LT population.


Assuntos
Transplante de Fígado , Criança , Humanos , Masculino , Feminino , Estudos de Casos e Controles , Estudos Retrospectivos , Terapia de Imunossupressão , Rejeição de Enxerto/epidemiologia , Sistema de Registros
10.
J Card Fail ; 30(2): 362-372, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37422273

RESUMO

BACKGROUND: Although numerous reports have studied the consequences of human leukocyte antigen (HLA) mismatching in renal transplantation, there are limited and outdated data analyzing this association in thoracic organ transplantation. Therefore, our study reviewed the impact of HLA mismatching at both the total and the loci levels in the modern-era heart-transplant procedure on survival and chronic rejection outcomes. METHODS: We performed a retrospective analysis of adult patients after heart transplant by using the United Network for Organ Sharing database from January 2005-July 2021. Total HLA and HLA-A, HLA-B and HLA-DR mismatches were analyzed. Survival and cardiac allograft vasculopathy were the outcomes of interest during a 10-year follow-up period using Kaplan-Meier curves, log-rank tests and multivariable regression models. RESULTS: A total of 33,060 patients were included in this study. Recipients with a high degree of HLA mismatching had increased incidences of acute organ rejection. There were no significant differences in mortality rates among any of the total or loci level groups. Similarly, there were no significant differences between total HLA mismatch groups in time to first cardiac allograft vasculopathy, though mismatching at the HLA-DR locus was associated with an increased risk of cardiac allograft vasculopathy. CONCLUSION: Our analysis suggests that HLA mismatch is not a significant predictor of survival in the modern era. Overall, the clinical implications of this study provide reassuring data for the continued use of non-HLA-matched donors in an effort to increase the donor pool. If HLA matching is to be considered for heart transplant donor-recipient selection, matching at the HLA-DR locus should take priority due to its association with cardiac allograft vasculopathy.


Assuntos
Insuficiência Cardíaca , Transplante de Coração , Adulto , Humanos , Estudos Retrospectivos , Sobrevivência de Enxerto , Rejeição de Enxerto/epidemiologia , Antígenos HLA-DR , Antígenos HLA
11.
Am J Nephrol ; 55(2): 235-244, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38035562

RESUMO

INTRODUCTION: ABO-incompatible (ABOi) living donor kidney transplantation (LDKT) is considered only for patients who do not have an ABO-compatible (ABOc) LD. Therefore, a clinically practical question is whether to proceed with ABOi LDKT or remain on dialysis while waiting for ABOc deceased donor kidney transplantation (DDKT). However, this issue has not been addressed in Asian countries, where ABOi LDKT programs are more active than DDKT programs. METHODS: A total of 426 patients underwent ABOi-LDKT between 2010 and 2020 at Seoul National University Hospital and Severance Hospital, Korea. We compared outcomes between the ABOi-LDKT and the propensity-matched control groups (waiting-list-only group, n = 1,278; waiting-list-or-ABOc-DDKT group, n = 1,278). RESULTS: The ABOi-LDKT group showed a significantly better patient survival rate than the waiting-list-only group (p = 0.001) and the waiting-list-or-ABOc-DDKT group (p = 0.048). When the ABOi-LDKT group was categorized into a high-titer group (peak anti-ABO titer ≥1:128) and a low-titer group (peak anti-ABO titer ≤1:64), the low-titer group showed better patient survival rates than those of the waiting-list-or-ABOc-DDKT group (p = 0.046) or the waiting-list-only group (p = 0.004). In contrast, the high-titer ABOi-LDKT group showed no significant benefit in patient survival compared to the waiting-list-or-ABOc-DDKT group. Death-censored graft survival in the ABOi-LDKT group was not significantly different from that in the ABOc-DDKT group (p = 0.563). CONCLUSION: The ABOi-LDKT group has better outcomes than the waiting-list-or-ABOc-DDKT group in a country with a long waiting time.


Assuntos
Transplante de Rim , Humanos , Doadores Vivos , Incompatibilidade de Grupos Sanguíneos , Rejeição de Enxerto/epidemiologia , Rim , Sistema ABO de Grupos Sanguíneos , Sobrevivência de Enxerto
12.
Am J Nephrol ; 55(4): 487-498, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38679014

RESUMO

INTRODUCTION: Kidney transplantation is a definitive treatment for end-stage renal disease. It is associated with improved life expectancy and quality of life. One of the most common complications following kidney transplantation is graft rejection. To our knowledge, no previous study has identified rejection risk factors in kidney transplant recipients in Saudi Arabia. Therefore, this study aimed to determine the specific risk factors of graft rejection. METHODS: A multicenter case-control study was conducted at four transplant centers in Saudi Arabia. All adult patients who underwent a renal transplant between January 1, 2015 and December 31, 2021 were screened for eligibility. Included patients were categorized into two groups (cases and control) based on the occurrence of biopsy-proven rejection within 2 years. The primary outcome was to determine the risk factors for rejection within the 2 years of transplant. Exact matching was utilized using a 1:4 ratio based on patients' age, gender, and transplant year. RESULTS: Out of 1,320 screened renal transplant recipients, 816 patients were included. The overall prevalence of 2-year rejection was 13.9%. In bivariate analysis, deceased donor status, the presence of donor-specific antibody (DSA), intraoperative hypotension, Pseudomonas aeruginosa, Candida, and any infection within 2 years were linked with an increased risk of 2-year rejection. However, in the logistic regression analysis, the presence of DSA was identified as a significant risk for 2-year rejection (adjusted OR: 2.68; 95% CI: 1.10, 6.49, p = 0.03). Furthermore, blood infection, infected with Pseudomonas aeruginosa or BK virus within 2 years of transplant, were associated with higher odds of 2-year rejection (adjusted OR: 3.10; 95% CI: 1.48, 6.48, p = 0.003, adjusted OR: 3.23; 95% CI: 0.87, 11.97, p = 0.08 and adjusted OR: 2.76; 95% CI: 0.89, 8.48, p = 0.07, respectively). CONCLUSION: Our findings emphasize the need for appropriate prevention and management of infections following kidney transplantation to avoid more serious problems, such as rejection, which could significantly raise the likelihood of allograft failure and probably death. Further studies with larger sample sizes are needed to investigate the impact of serum chloride levels prior to transplant and intraoperative hypotension on the risk of graft rejection and failure.


Assuntos
Rejeição de Enxerto , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Masculino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/epidemiologia , Feminino , Estudos de Casos e Controles , Fatores de Risco , Adulto , Pessoa de Meia-Idade , Arábia Saudita/epidemiologia , Falência Renal Crônica/cirurgia , Fatores de Tempo
13.
Am J Nephrol ; 55(4): 477-486, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38498992

RESUMO

INTRODUCTION: Hepatitis B virus (HBV) infection is prevalent in Asia including Taiwan. We retrospectively evaluated the risk of HBV reactivation and clinical outcomes in HBV+ and HBV- kidney transplant recipients. METHODS: Patients who underwent kidney transplantation between January 2004 and December 2021 were reviewed. The outcomes of interest included risks of HBV reactivation and patient/graft survival. RESULTS: We identified 337 patients (47.5 ± 12 years) in our final cohort. Fifty-two (15.4%) had hepatitis B surface antigen (HBsAg) positive at the time of transplantation. Seventeen developed viral reactivations, with 41.2% of them accompanied by active hepatitis. The graft survival, acute rejection rate, and cancer development after kidney transplantation did not differ in terms of HBsAg status. The Cox multivariate analysis indicated the HBV reactivation risk was increased by a lack of pretransplant anti-HBV medication (hazard ratio [HR], 5.95; 95% confidence interval [CI], 1.31-27.02; p = 0.021) or an absence of lifelong antiviral therapy (HR: 3.14; 95% CI: 1.01-9.74; p = 0.047). CONCLUSION: Individuals, independent of HBsAg status, had similar prognosis in terms of patient and graft survival, acute rejection rate, and cancer development. The absence of either pretransplant anti-HBV medication or lifelong antiviral therapy was significantly associated with an increased risk of HBV reactivation.


Assuntos
Rejeição de Enxerto , Sobrevivência de Enxerto , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Transplante de Rim , Ativação Viral , Humanos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Feminino , Estudos Retrospectivos , Fatores de Risco , Adulto , Ativação Viral/imunologia , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/epidemiologia , Hepatite B/complicações , Antivirais/uso terapêutico , Taiwan/epidemiologia
14.
Liver Int ; 44(2): 411-421, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38010995

RESUMO

BACKGROUND AND AIMS: The importance of human leukocyte antigen (HLA) matching between liver transplant donors and recipients on graft survival remains unclear and is not a clinical consideration in liver transplantation. This study aimed to determine the relationship between HLA matching and liver graft survival using a large-scale multi-centre database (UNOS/OPTN) and multivariate logistic analysis. The secondary aim was to determine whether this relationship was influenced by transplant indication and donor status. METHODS: This retrospective observational analysis was performed using 22 702 liver transplant recipients from the UNOS/OPTN database. Patients were divided into two groups based on number of HLA mismatches (0-3 mismatches vs. 4-6 mismatches) and then subcategorized by indication and donor status. Risk-adjusted outcomes were assessed by multivariate Cox analysis adjusting for donor and recipient characteristics and visualized using Kaplan-Meier survival curves. RESULTS: Allograft survival and risk of acute rejection were associated with degree of HLA mismatch. This association between HLA mismatch and graft survival persisted in individuals who underwent transplant for hepatitis, metabolic, drug toxicity, and congenital indications. Donor status also influenced the relationship between HLA mismatch and graft survival. Graft survival in DBD recipients was longer than in DCD in the 4-6 HLA mismatch group, whereas no significant difference was found in the 0-3 HLA mismatch group. CONCLUSION: HLA mismatch significantly reduced graft survival and increased risk of acute rejection. This association was noted only in specific indications. These findings are of potential clinical relevance to organ allocation, allograft matching algorithms, immunosuppression protocols, and transplant surveillance.


Assuntos
Sobrevivência de Enxerto , Transplante de Fígado , Humanos , Estudos Retrospectivos , Rejeição de Enxerto/epidemiologia , Teste de Histocompatibilidade , Doadores de Tecidos , Antígenos HLA
15.
J Surg Res ; 300: 253-262, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38833753

RESUMO

INTRODUCTION: Obesity is frequent among organ transplant recipients, increasing the risk of acute graft rejection and overall morbimortality. Laparoscopic sleeve gastrectomy (LSG) effectively improves graft survival and associated comorbidities. We first compared 30-d outcomes between chronic immunosuppressed (CI) and nonchronic immunosuppressed (non-CI) patients. Then, between organ transplant and non-organ transplant CI patients who underwent LSG. METHODS: Patients who underwent LSG within the metabolic and bariatric surgery accreditation and quality improvement program 2017-2019 were included. Using 1:1 and 1:4 propensity score matching analysis, the cohorts were matched for 30 characteristics. We then compared 30-d outcomes between CI and non-CI (analysis 1) and between organ transplant and non-organ transplant CI patients who underwent LSG (analysis 2). RESULTS: A total of 486,576 patients were included. The matched cohorts in analysis 1 (n = 8978) and analysis 2 (n = 1152, n = 371) had similar preoperative characteristics. Propensity score matching in analysis 1 showed that patients in the CI group had significantly higher rates of renal complications (0.4% versus 0.2%, P = 0.006), unplanned intensive care unit admission (1.1% versus 0.7%, P = 0.003), blood transfusions (1.1% versus 0.7%, P = 0.003), readmissions (4.6% versus 3.5%, P < 0.001), reoperations (1.4% versus 1.0%, P = 0.033), interventions (1.3% versus 1.0%, P = 0.026), and postoperative bleeding (0.6% versus 0.4%, P = 0.013). In analysis 2, patients with organ transplant CI had a higher rate of pulmonary complications (1.1% versus 0.3%, P = 0.043), renal complications (2.4% versus 0.2%, P < 0.001), blood transfusions (6.5% versus 1.3%, P < 0.001), and readmissions (10.0% versus 4.6%, P < 0.001). CONCLUSIONS: Patients with transplant-related CI who underwent LSG have higher 30-d postoperative complication rates compared to nontransplant-related CI patients; however, there were no differences in terms of mortality, intensive care unit admissions, staple line leaks, or bleeding. LSG is safe and feasible in this high-risk population.


Assuntos
Gastrectomia , Transplante de Órgãos , Complicações Pós-Operatórias , Humanos , Masculino , Feminino , Gastrectomia/efeitos adversos , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Transplante de Órgãos/efeitos adversos , Pontuação de Propensão , Resultado do Tratamento , Laparoscopia/efeitos adversos , Terapia de Imunossupressão/efeitos adversos , Sobrevivência de Enxerto , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/etiologia
16.
J Surg Res ; 300: 477-484, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38875946

RESUMO

BACKGROUND: Donor blood transfusion may potentially affect transplant outcomes through an inflammatory response, recipient sensitization, or transmission of infection. The aim of this study was to evaluate the association of donor blood transfusion with outcomes of liver transplantation (LT). METHODS: From January 2004 to December 2022, donor blood transfusion information was available for 113,017 adult recipients of LT in the United Network for Organ Sharing database and was classified into 4 levels of transfusion: no-transfusion (N = 68,130), transfusion of 1-5 units (N = 33,629), 6-10 units (N = 8067), and >10 units (N = 5329). Recipient survival analysis was performed by Kaplan-Meier method and multivariable Cox-hazard model. RESULTS: Among this cohort, 40.8% of donors (N = 46,261) received blood transfusion during the index hospitalization. Compared to no-blood transfusion donors, blood transfusion donors were younger (median age 37 versus 46 y P < 0.001) and were more brain death donors (94.5% versus 92.1%, P < 0.001). An increased risk of rejection at 6-mo (transfusion 10.3% versus no-transfusion 9.9%, P = 0.055) and 1 y (transfusion 12.5% versus no-transfusion 11.9%, P = 0.0036) post-LT was noted in this cohort. Multivariable Cox-hazard model showed blood transfusion was associated with increased 1-y mortality (transfusion 1.07; 95% CI 1.02-1.12, P = 0.007) and graft failure (transfusion 1.09; 95% CI 1.04-1.13, P < 0.001). CONCLUSIONS: Donor blood transfusion was associated with an increased risk of rejection at 6 mo and 1 y among LT recipients and worse post-transplant graft and overall survival. Additional information regarding donor blood transfusion, along with other known factors, may be considered when deciding the optimization of overall immune suppression in LT recipients to decrease the risk of delayed rejection.


Assuntos
Transfusão de Sangue , Transplante de Fígado , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/estatística & dados numéricos , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Feminino , Adulto , Estados Unidos/epidemiologia , Transfusão de Sangue/estatística & dados numéricos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Estudos Retrospectivos , Idoso , Doadores de Tecidos/estatística & dados numéricos , Resultado do Tratamento
17.
Clin Transplant ; 38(2): e15264, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38375934

RESUMO

BACKGROUND: The association between cannabis use and access to waitlisting, transplantation, and post-transplant outcomes remains uncertain. METHODS: Patients referred for kidney transplant (KT) to the University Health Network from January 1, 2003, to June 30, 2020, and followed until December 31, 2020, were included. Predictors of reported cannabis use were examined using a logistic regression model. The association between cannabis use and time to clearance for KT, undergoing KT, and post-transplant outcomes was evaluated using Cox proportional hazards models. RESULTS: Among 3734 patients, the prevalence of reported cannabis use was 11.8%. Cannabis use was associated with a lower likelihood of KT clearance (adjusted hazard ratio [aHR] .82 [95% confidence interval (CI): .72, .94]). Once cleared for KT, cannabis use did not predict the subsequent receipt of KT (aHR .92, [95% CI: .79, 1.08]). Among 2091 KT recipients, cannabis use was associated with a higher likelihood of biopsy-proven acute rejection (aHR 1.55, [95% CI: 1.06, 2.27]). The relative hazard of death-censored graft failure was similarly elevated (aHR 1.60 [95% CI: .95, 2.72]). Cannabis use did not predict total graft failure (aHR 1.33 [95% CI: .90, 1.96]), death with graft function (aHR 1.06 [95% CI: .59, 1.89]), or hospital readmission in the first-year post-transplant (aHR 1.26 [95% CI: .95, 1.68]). CONCLUSIONS: Cannabis users have less access to transplantation and an increased risk of acute rejection, possibly leading to more graft loss. Further studies are warranted to understand possible mechanisms for the increased risk of allograft immune injury among cannabis users.


Assuntos
Cannabis , Transplante de Rim , Humanos , Transplante de Rim/efeitos adversos , Modelos de Riscos Proporcionais , Modelos Logísticos , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Fatores de Risco , Sobrevivência de Enxerto
18.
Clin Transplant ; 38(1): e15246, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38289885

RESUMO

BACKGROUND: Experience with lung transplantation (LT) in patients with human immunodeficiency virus (HIV) is limited. Many studies have demonstrated the success of kidney and liver transplantation in HIV-seropositive (HIV+) patients. Our objective was to conduct a national registry analysis comparing LT outcomes in HIV+ to HIV-seronegative (HIV-) recipients. METHODS: The United Network for Organ Sharing database was queried to identify LTs performed in adult HIV+ patients between 2016 and 2023. Patients with unknown HIV status, multiorgan transplants, and redo transplants were excluded. The primary endpoints were mortality and graft rejection. Survival time was analyzed using Kaplan-Meier analysis. RESULTS: The study included 17 487 patients, 67 of whom were HIV+. HIV+ recipients were younger (59 vs. 62 years, p = .02), had higher pulmonary arterial pressure (28 vs. 25 mm Hg, p = .04), and higher lung allocation scores (47 vs. 41, p = .01) relative to HIV- recipients. There were no differences in graft/recipient survival time between groups. HIV+ recipients had higher rates of post-transplant dialysis (18% vs. 8.4%, p = .01), but otherwise had similar post-transplant outcomes to HIV-recipients. CONCLUSIONS: This national registry analysis suggests LT outcomes in HIV+ patients are not inferior to outcomes in HIV- patients and that well-selected HIV+ recipients can achieve comparable patient and graft survival rates relative to HIV- recipients.


Assuntos
Infecções por HIV , Transplante de Pulmão , Adulto , Humanos , HIV , Sobrevivência de Enxerto , Sistema de Registros , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/etiologia , Infecções por HIV/complicações , Infecções por HIV/cirurgia
19.
Clin Transplant ; 38(7): e15403, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39023089

RESUMO

BACKGROUND: The application of posttransplant predictive models is limited by their poor statistical performance. Neglecting the dynamic evolution of demographics and medical practice over time may be a key issue. OBJECTIVES: Our objective was to develop and validate era-specific predictive models to assess whether these models could improve risk stratification compared to non-era-specific models. METHODS: We analyzed the United Network for Organ Sharing (UNOS) database including first noncombined heart transplantations (2001-2018, divided into four transplant eras: 2001-2005, 2006-2010, 2011-2015, 2016-2018). The endpoint was death or retransplantation during the 1st-year posttransplant. We analyzed the dynamic evolution of major predictive variables over time and developed era-specific models using logistic regression. We then performed a multiparametric evaluation of the statistical performance of era-specific models and compared them to non-era-specific models in 1000 bootstrap samples (derivation set, 2/3; test set, 1/3). RESULTS: A total of 34 738 patients were included, 3670 patients (10.5%) met the composite endpoint. We found a significant impact of transplant era on baseline characteristics of donors and recipients, medical practice, and posttransplant predictive models, including significant interaction between transplant year and major predictive variables (total serum bilirubin, recipient age, recipient diabetes, previous cardiac surgery). Although the discrimination of all models remained low, era-specific models significantly outperformed the statistical performance of non-era-specific models in most samples, particularly concerning discrimination and calibration. CONCLUSIONS: Era-specific models achieved better statistical performance than non-era-specific models. A regular update of predictive models may be considered if they were to be applied for clinical decision-making and allograft allocation.


Assuntos
Transplante de Coração , Humanos , Transplante de Coração/efeitos adversos , Transplante de Coração/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Seguimentos , Prognóstico , Fatores de Risco , Sobrevivência de Enxerto , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Adulto , Taxa de Sobrevida , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Medição de Risco/métodos , Estudos Retrospectivos
20.
Clin Transplant ; 38(9): e15299, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39268639

RESUMO

BACKGROUND: There is a lack of information on the waitlist performance and post-transplant outcomes of lung transplants in elderly recipients in Korea. METHODS: We retrospectively reviewed and analyzed data from the Korean Network for Organ Sharing database between March 2010 and August 2023. RESULTS: In total, 2574 patients were listed for lung transplantation during the study period, with 511 (19.9%) of them being over 65 years of age. Among these, 188 patients (36.8%) underwent transplantation, while 184 patients (36%) passed away without undergoing transplantation at the time of data extraction. The most prevalent underlying disease on the waitlist was idiopathic pulmonary fibrosis, accounting for 68.1%. The 1-year survival rate was significantly lower in the elderly compared to that in the nonelderly (65.4 vs. 75.4%; p = .004). In the multivariate Cox analysis, elderly (hazard ratio [HR], 1.49; 95% CI, 1.14-1.97; p = .004) and a high urgent status at registration (HR, 1.83; 95% CI, 1.40-2.40; p < .001) were significantly associated with post-transplant 1-year mortality. Kaplan-Meier curves demonstrated a significant difference in post-transplant mortality based on the urgency status at enrollment (χ2 = 8.302, p = .016). Even with the same highly urgent condition at the time of transplantation, different prognoses were observed depending on the condition at listing (χ2 = 9.056, p = .029). CONCLUSION: The elderly exhibited worse transplant outcomes than nonelderly adults, with a highly urgent status at registration identified as a significant risk factor. Unprepared, highly urgent transplantation was associated with poor outcomes.


Assuntos
Transplante de Pulmão , Listas de Espera , Humanos , Transplante de Pulmão/mortalidade , Masculino , Feminino , Listas de Espera/mortalidade , República da Coreia/epidemiologia , Estudos Retrospectivos , Idoso , Pessoa de Meia-Idade , Taxa de Sobrevida , Seguimentos , Prognóstico , Fatores de Risco , Adulto , Sobrevivência de Enxerto , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Complicações Pós-Operatórias/mortalidade , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/mortalidade , Rejeição de Enxerto/epidemiologia , Pneumopatias/cirurgia , Pneumopatias/mortalidade
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