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1.
Transplant Proc ; 53(5): 1470-1476, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34006380

RESUMO

BACKGROUND: In kidney transplantation (KT), delayed graft function (DGF) is a significant early complication observed in the first week. The study aimed to investigate the impact of DGF on the outcome, allograft, and patient survival after KT with organs from deceased donors. METHODS: This retrospective study was conducted using 304 KT patients who received an organ from deceased donors from 2008 to 2018. The patients were divided into 2 groups, DGF positive (DGF+) and DGF negative (DGF-). The database containing the clinical, laboratory, and immunologic information of donors and recipients was statistically analyzed using the SSPS program. RESULTS: In this study, 189 (62.17%) were DGF+ and 115 (37.83%) were DGF-. Until 6 months after KT, the estimate glomerular filtration rate was better in group DGF-, but it was similar between the groups during 10-year follow-up. Graft losses were higher in DGF+ group than in the DGF- (P = .046). The serum creatinine level was persistently higher in DGF+ group until the sixth month (P ≤ .05). Allograft survival rates were better in patients who were DGF- (P = .033). Those who had DGF for more than 15 days had a worse graft survival (P = .003), but in 10 year follow-up, patient survival rates were similar (P = .705). CONCLUSION: DGF+ patients were associated with dialysis time before KT, ischemia time, and the donors' clinical status, such as age, organ quality, and serum creatinine. All these factors had a great impact on graft survival but not on patient survival.


Assuntos
Função Retardada do Enxerto/mortalidade , Sobrevivência de Enxerto , Transplante de Rim/efeitos adversos , Adulto , Aloenxertos/fisiopatologia , Creatinina/sangue , Função Retardada do Enxerto/etiologia , Taxa de Filtração Glomerular , Humanos , Rim/fisiopatologia , Masculino , Pessoa de Meia-Idade , Diálise Renal/efeitos adversos , Estudos Retrospectivos , Taxa de Sobrevida , Doadores de Tecidos/estatística & dados numéricos , Transplante Homólogo , Resultado do Tratamento
2.
Transplant Proc ; 53(5): 1462-1469, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33579551

RESUMO

Delayed graft function (DGF) after kidney transplantation is associated with an increased risk of graft failure. We studied the histologic findings among adult kidney transplant recipients transplanted between January 2000 and June 2015 who had DGF and had a kidney biopsy within 14 days of transplant. Death censored graft failure (DCGF) and death at 1 and 3 years after transplant were examined. A total of 269 transplant recipients fulfilled our selection criteria, of which 152 (56.51%) had acute tubular necrosis (ATN), 44 (16.4%) had acute rejection (AR), mainly T-cell mediated rejection (n = 31), 35 (13%) had ATN with AR (mainly T-cell mediated rejection, n = 26), and 38 (14.1%) had other pathology. Compared with those with ATN alone, kidney transplant recipients with AR alone had a significantly higher risk of DCGF at 1 year post transplant (adjusted hazard ratio = 3.70; 95% confidence interval 1.5-9.5; P = .006). Those with AR alone had an increased risk of DCGF at 3 years post transplant (hazard ratio = 3.10; 95% confidence interval 1.3-8.5; P = .01) in crude analyses. There was no association between DGF etiology and mortality. Early renal biopsy can be used to distinguish AR, which has protocolized treatments, from other etiologies. This could potentially alter allograft survival within 1 year of transplant complicated by DGF.


Assuntos
Biópsia/estatística & dados numéricos , Função Retardada do Enxerto/mortalidade , Rejeição de Enxerto/mortalidade , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/mortalidade , Adulto , Função Retardada do Enxerto/etiologia , Função Retardada do Enxerto/patologia , Feminino , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Humanos , Incidência , Rim/patologia , Necrose Tubular Aguda/etiologia , Necrose Tubular Aguda/mortalidade , Necrose Tubular Aguda/patologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/patologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Transplantes/patologia
3.
Transplantation ; 105(4): 876-885, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32769629

RESUMO

BACKGROUND: Deceased-donor kidneys experience extensive injury, activating adaptive and maladaptive pathways therefore impacting graft function. We evaluated urinary donor uromodulin (UMOD) and osteopontin (OPN) in recipient graft outcomes. METHODS: Primary outcomes: all-cause graft failure (GF) and death-censored GF (dcGF). Secondary outcomes: delayed graft function (DGF) and 6-month estimated glomerular filtration rate (eGFR). We randomly divided our cohort of deceased donors and recipients into training and test datasets. We internally validated associations between donor urine UMOD and OPN at time of procurement, with our primary outcomes. The direction of association between biomarkers and GF contrasted. Subsequently, we evaluated UMOD:OPN ratio with all outcomes. To understand these mechanisms, we examined the effect of UMOD on expression of major histocompatibility complex II in mouse macrophages. RESULTS: Doubling of UMOD increased dcGF risk (adjusted hazard ratio [aHR], 1.1; 95% confidence interval [CI], 1.02-1.2), whereas OPN decreased dcGF risk (aHR, 0.94; 95% CI, 0.88-1). UMOD:OPN ratio ≤3 strengthened the association, with reduced dcGF risk (aHR, 0.57; 0.41-0.80) with similar associations for GF, and in the test dataset. A ratio ≤3 was also associated with lower DGF (aOR, 0.73; 95% CI, 0.60-0.89) and higher 6-month eGFR (adjusted ß coefficient, 3.19; 95% CI, 1.28-5.11). UMOD increased major histocompatibility complex II expression elucidating a possible mechanism behind UMOD's association with GF. CONCLUSIONS: UMOD:OPN ratio ≤3 was protective, with lower risk of DGF, higher 6-month eGFR, and improved graft survival. This ratio may supplement existing strategies for evaluating kidney quality and allocation decisions regarding deceased-donor kidney transplantation.


Assuntos
Função Retardada do Enxerto/etiologia , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Transplante de Rim/efeitos adversos , Rim/cirurgia , Osteopontina/urina , Doadores de Tecidos , Uromodulina/urina , Adulto , Idoso , Animais , Biomarcadores/urina , Células Cultivadas , Função Retardada do Enxerto/mortalidade , Função Retardada do Enxerto/fisiopatologia , Feminino , Antígenos de Histocompatibilidade Classe II/metabolismo , Humanos , Rim/fisiopatologia , Transplante de Rim/mortalidade , Macrófagos/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Estados Unidos
4.
Front Immunol ; 11: 1886, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32983110

RESUMO

Delayed graft function (DGF) occurs in a significant proportion of deceased donor kidney transplant recipients and was associated with graft injury and inferior clinical outcome. The aim of the present multi-center study was to identify the immunological and non-immunological predictors of DGF and to determine its influence on outcome in the presence and absence of human leukocyte antigen (HLA) antibodies. 1,724 patients who received a deceased donor kidney transplant during 2008-2017 and on whom a pre-transplant serum sample was available were studied. Graft survival during the first 3 post-transplant years was analyzed by multivariable Cox regression. Pre-transplant predictors of DGF and influence of DGF and pre-transplant HLA antibodies on biopsy-proven rejections in the first 3 post-transplant months were determined by multivariable logistic regression. Donor age ≥50 years, simultaneous pre-transplant presence of HLA class I and II antibodies, diabetes mellitus as cause of end-stage renal disease, cold ischemia time ≥18 h, and time on dialysis >5 years were associated with increased risk of DGF, while the risk was reduced if gender of donor or recipient was female or the reason for death of donor was trauma. DGF alone doubled the risk for graft loss, more due to impaired death-censored graft than patient survival. In DGF patients, the risk of death-censored graft loss increased further if HLA antibodies (hazard ratio HR=4.75, P < 0.001) or donor-specific HLA antibodies (DSA, HR=7.39, P < 0.001) were present pre-transplant. In the presence of HLA antibodies or DSA, the incidence of biopsy-proven rejections, including antibody-mediated rejections, increased significantly in patients with as well as without DGF. Recipients without DGF and without biopsy-proven rejections during the first 3 months had the highest fraction of patients with good kidney function at year 1, whereas patients with both DGF and rejection showed the lowest rate of good kidney function, especially when organs from ≥65-year-old donors were used. In this new era of transplantation, besides non-immunological factors, also the pre-transplant presence of HLA class I and II antibodies increase the risk of DGF. Measures to prevent the strong negative impact of DGF on outcome are necessary, especially during organ allocation for presensitized patients.


Assuntos
Função Retardada do Enxerto/imunologia , Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Isoanticorpos/sangue , Transplante de Rim/efeitos adversos , Adulto , Idoso , Biomarcadores/sangue , Função Retardada do Enxerto/sangue , Função Retardada do Enxerto/diagnóstico , Função Retardada do Enxerto/mortalidade , Europa (Continente) , Feminino , Rejeição de Enxerto/sangue , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto , Humanos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
5.
Prog Transplant ; 30(4): 342-348, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32930044

RESUMO

BACKGROUND: The effects of delayed graft function on long-term kidney allograft outcomes are poorly defined among simultaneous liver and kidney transplant recipients. METHODS: We analyzed data of all simultaneous liver and kidney recipients transplanted at the University of Wisconsin between 2010 and 2017. Risk factors for the development of delayed graft function, kidney graft failure, and patient mortality were outcomes of interest. RESULTS: There were a total of 60 simultaneous liver and kidney recipients; 28 (47%) had delayed graft function. After adjustment for multiple variables, we found that pretransplant dialysis >6 weeks (hazard ratio [HR] = 5.6, 95% CI: 1.23-25.59, P = .02), pretransplant albumin <3 g/dL (HR = 5.75, 95% CI: 1.76-16.94, P = .003), and presence of pretransplant diabetes (HR = 2.5, 95% CI: 0.97-4.77, P = .05) were significantly associated with delayed graft function. Multivariate analysis showed that pretransplant albumin <3 (HR = 4.86, 95% CI: 1.07-22.02, P = .02) was associated with a higher risk of all-cause kidney allograft failure, whereas the duration of delayed graft function (HR = 1.07 per day, 95% CI: 1.01-1.14, P = .01) was associated with a higher risk of death-censored kidney allograft failure. The presence of delayed graft function was not associated with all-cause or death-censored kidney or liver allograft failure. Similarly, the presence of delayed graft function was not associated with patient mortality. CONCLUSION: The incidence of delayed graft function was high in simultaneous liver and kidney recipients. However, with appropriate management, delayed graft function may not have a negative impact on patient or kidney allograft survival.


Assuntos
Comorbidade , Função Retardada do Enxerto/fisiopatologia , Rejeição de Enxerto/fisiopatologia , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Falência Hepática Aguda/cirurgia , Transplante de Fígado/efeitos adversos , Transplante Homólogo/efeitos adversos , Adulto , Fatores Etários , Idoso , Função Retardada do Enxerto/mortalidade , Feminino , Rejeição de Enxerto/mortalidade , Humanos , Incidência , Falência Renal Crônica/epidemiologia , Transplante de Rim/mortalidade , Falência Hepática Aguda/epidemiologia , Transplante de Fígado/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Fatores de Risco , Fatores Sexuais , Transplante Homólogo/mortalidade , Wisconsin/epidemiologia
6.
Transplant Proc ; 52(5): 1536-1538, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32252998

RESUMO

BACKGROUND: Donation after circulatory death (DCD) is a solid resource to widen the kidney donor pool. Italian activity has grown in the last years with encouraging results. Our center has been active in DCD kidney transplantation (KTX) since November 2017, providing 22.5% of Italian DCD donations in 2018. We present a single-center retrospective analysis after a 1-year follow-up comparing DCD and donation after brain death (DBD) KTX outcomes. METHODS: DCD (controlled only) and DBD KTX performed in our center from November 2017 to December 2018 were considered. All DCDs underwent in situ normothermic perfusion with extracorporeal membrane oxygenation, ex situ hypothermic oxygenated perfusion, and renal biopsy prior to allocation. We considered features of donors and recipients, immunosuppressive regimen, delayed graft function (DGF), primary nonfunction (PNF), graft and patient survival (Kaplan-Meier), creatinine, and estimated glomerular filtration rate at 1 year. Mean comparison with a Student t test and with χ2 test for frequencies were elaborated. RESULTS: Twenty-eight DBD, 18 double (64.3%) and 10 single (35.7%), were performed; 7 DCD, 3 double (42.8%) and 4 single (57.2%), were performed. By comparing single and double KTX, no statistically significant difference was found. We recorded 7 DGFs (25%) in DBD and 1 (14.3%) in the DCD group (P > .99) and no PNF. No graft was lost during the first year. One-year estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration) was, respectively, 62.7 ± 25.3 and 54.71 ± 14.66 mL/min (P = .25). DBD patient survival rate was 92.8%, DCD was 100%, and Kaplan-Meier was not statistically significant (P = .72). CONCLUSIONS: Controlled DCD is a valid resource for KTX, with similar outcomes to DBD. A multidisciplinary donor evaluation, combining clinical, perfusion, and histologic data in the allocation process, allows excellent results.


Assuntos
Morte Encefálica , Morte , Transplante de Rim/mortalidade , Doadores de Tecidos/estatística & dados numéricos , Adulto , Função Retardada do Enxerto/mortalidade , Feminino , Seguimentos , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Itália , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Perfusão , Estudos Retrospectivos , Taxa de Sobrevida
7.
Transplant Proc ; 52(1): 119-126, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31901319

RESUMO

PURPOSE: We investigated whether older donor kidneys aged >75 years have acceptable long-term function and if recipients can benefit sufficiently from the transplantation. METHODS: This single-center study retrospectively analyzed patient data from 217 deceased donor kidney transplants performed between 1998 and 2014 as part of the Eurotransplant Senior Program, where the organ donors were ≥65 years old. Depending on donor age, the groups "older donors" (OD; n = 161) and "very old donors" (VOD; n = 56) received transplants from donors aged 65 to 75 years and >75 years, respectively. Donor and recipient clinical characteristics, delayed graft function, estimated glomerular filtration rate, 1-year rejection rate, patient and graft survival, and postoperative complications were investigated. RESULTS: Comparing VOD group vs OD group, the 1-year, 3-year, and 5-year graft survival rates were 80.4% vs 76.4%, 62.5% vs 65.8%, and 42.6% vs 57.3%, respectively. Patient survival rates after 1, 3, and 5 years were 89.3% vs 88.2%, 71.4% vs 78.2%, and 57.5% vs 71.8%, respectively. There were no significant differences between the 2 groups (graft survival P = .107; patient survival P = .126). Kidney graft function after 1, 2, and 3 years was significantly better in the OD group than in the VOD group. No differences were found regarding postoperative complications, rejection rate, and delayed graft function. CONCLUSION: The utilization of selected kidney-grafts from donors >75 years resulted in acceptable outcomes after kidney transplantation and could expand the donor pool. In contrast to the high mortality rate during dialysis, recipients in both groups benefited from transplantation.


Assuntos
Transplante de Rim/métodos , Doadores de Tecidos/provisão & distribuição , Transplantes/estatística & dados numéricos , Adulto , Idoso , Morte Encefálica , Função Retardada do Enxerto/etiologia , Função Retardada do Enxerto/mortalidade , Feminino , Taxa de Filtração Glomerular , Sobrevivência de Enxerto , Humanos , Rim , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
8.
Am J Transplant ; 20(1): 137-144, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31278819

RESUMO

To date, thousands of living donor kidneys have been shipped through kidney paired donation (KPD). To expand on this growing segment of living donor transplantation, we evaluated the effect of advanced age donation ("oldest kidneys") and prolonged cold ischemia time ("coldest kidneys") on graft function and survival using the National Kidney Registry database from February 2008 to May 2018. Donors were stratified by age at time of donation (<65 or ≥65 years) and kidneys were stratified by cold ischemia time (<16 or ≥16 hours). We evaluated delayed graft function and death-censored graft failure (DCGF) for up to seven posttransplant years. Of the 2363 shipped living donor kidney transplants, 4.1% of donors were ≥65 years and 6.0% of transplanted kidneys had cold ischemia times ≥16 hours. Delayed graft function and DCGF occurred in 5.2% and 4.7% of cases. There were no significant associations between delayed graft function and donor age (P = .947) or cold ischemia (P = .532). Donor age and cold ischemia time were not predictive of delayed graft function (OR = 0.86,1.20; P = .8, .6) or DCGF (HR = 1.38,0.35, P = .5, .1). These findings may alleviate concerns surrounding the utilization of kidneys from older donors or those originating from distant transplant centers.


Assuntos
Isquemia Fria/estatística & dados numéricos , Rejeição de Enxerto/mortalidade , Transplante de Rim/mortalidade , Doadores Vivos/provisão & distribuição , Preservação de Órgãos/mortalidade , Coleta de Tecidos e Órgãos/métodos , Meios de Transporte/métodos , Adolescente , Adulto , Idoso , Função Retardada do Enxerto/etiologia , Função Retardada do Enxerto/mortalidade , Função Retardada do Enxerto/patologia , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Falência Renal Crônica/mortalidade , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Fatores de Risco , Taxa de Sobrevida , Adulto Jovem
9.
Clin J Am Soc Nephrol ; 15(1): 109-116, 2020 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-31843975

RESUMO

BACKGROUND AND OBJECTIVES: Delayed graft function is related to ischemia-reperfusion injury and may be complement dependent. We previously reported from a randomized, placebo-controlled trial that treatment with C1 esterase inhibitor was associated with a shorter duration of delayed graft function and higher eGFR at 1 year. Here, we report longer-term outcomes from this trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a post hoc analysis of a phase 1/2, randomized, controlled trial enrolling 70 recipients of deceased donor kidney transplants at risk for delayed graft function (NCT02134314). Subjects were randomized to receive C1 esterase inhibitor 50 U/kg (n=35) or placebo (n=35) intraoperatively and at 24 hours. The cumulative incidence functions method was used to compare graft failure and death over 3.5 years. eGFR slopes were compared using a linear mixed effects model. RESULTS: Three deaths occurred among C1 esterase inhibitor-treated patients compared with none receiving placebo. Seven graft failures developed in the placebo group compared with one among C1 esterase inhibitor-treated recipients; the cumulative incidence of graft failure was lower over 3.5 years among C1 esterase inhibitor-treated recipients compared with placebo (P=0.03). Although no difference in eGFR slopes was observed between groups (P for group-time interaction =0.12), eGFR declined in placebo-treated recipients (-4 ml/min per 1.73 m2 per year; 95% confidence interval, -8 to -0.1) but was stable in C1 esterase inhibitor-treated patients (eGFR slope: 0.5 ml/min per 1.73 m2 per year; 95% confidence interval, -4 to 5). At 3.5 years, eGFR was 56 ml/min per 1.73 m2 (95% confidence interval, 42 to 70) in the C1 esterase inhibitor group versus 35 ml/min per 1.73 m2 (95% confidence interval, 21 to 48) in the placebo group, with an estimated mean eGFR difference of 21 ml/min per 1.73 m2 (95% confidence interval, 2 to 41 ml/min per 1.73 m2). CONCLUSIONS: Treatment of patients at risk for ischemia-reperfusion injury and delayed graft function with C1 esterase inhibitor was associated with a lower incidence of graft failure.


Assuntos
Proteína Inibidora do Complemento C1/uso terapêutico , Função Retardada do Enxerto/prevenção & controle , Taxa de Filtração Glomerular/efeitos dos fármacos , Transplante de Rim , Rim/efeitos dos fármacos , Traumatismo por Reperfusão/prevenção & controle , Adulto , Proteína Inibidora do Complemento C1/efeitos adversos , Função Retardada do Enxerto/etiologia , Função Retardada do Enxerto/mortalidade , Função Retardada do Enxerto/fisiopatologia , Método Duplo-Cego , Feminino , Humanos , Incidência , Rim/fisiopatologia , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/mortalidade , Traumatismo por Reperfusão/fisiopatologia , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
10.
Ann Surg ; 270(5): 877-883, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31567503

RESUMO

OBJECTIVE: To explore putative different impacts of delayed graft function (DGF) on long-term graft survival in kidneys donated after brain death (DBD) and circulatory death (DCD). BACKGROUND: Despite a 3-fold higher incidence of DGF in DCD grafts, large studies show equivalent long-term graft survival for DBD and DCD grafts. This observation implies a differential impact of DGF on DBD and DCD graft survival. The contrasting impact is remarkable and yet unexplained. METHODS: The impact of DGF on DBD and DCD graft survival was evaluated in 6635 kidney transplants performed in The Netherlands. DGF severity and functional recovery dynamics were assessed for 599 kidney transplants performed at the Leiden Transplant Center. Immunohistochemical staining, gene expression profiling, and Ingenuity Pathway Analysis were used to identify differentially activated pathways in DBD and DCD grafts. RESULTS: While DGF severely impacted 10-year graft survival in DBD grafts (HR 1.67; P < 0.001), DGF did not impact graft survival in DCD grafts (HR 1.08; P = 0.63). Shorter dialysis periods and superior posttransplant eGFRs in DBD grafts show that the differential impact was not caused by a more severe DGF phenotype in DBD grafts. Immunohistochemical evaluation indicates that pathways associated with tissue resilience are present in kidney grafts. Molecular evaluation showed selective activation of resilience-associated pathways in DCD grafts. CONCLUSIONS: This study shows an absent impact of DGF on long-term graft survival in DCD kidneys. Molecular evaluation suggests that the differential impact of DGF between DBD and DCD grafts relates to donor-type specific activation of resilience pathways in DCD grafts.


Assuntos
Função Retardada do Enxerto/fisiopatologia , Falência Renal Crônica/cirurgia , Transplante de Rim/mortalidade , Transplante de Rim/métodos , Sistema de Registros , Idoso , Análise de Variância , Morte Encefálica , Função Retardada do Enxerto/mortalidade , Estudos de Avaliação como Assunto , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Insuficiência Cardíaca/mortalidade , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Países Baixos , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Medição de Risco , Fatores de Tempo , Doadores de Tecidos
11.
Transplantation ; 103(12): 2645-2653, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31343572

RESUMO

BACKGROUND: Chronic lung allograft dysfunction (CLAD) limits long-term survival after lung transplantation (LTx). Early detection or prediction of CLAD can lead to changes in patient management that, in turn, may improve prognosis. The purpose of this study was to investigate the utility of quantitative computed tomography (CT) lung density analysis in early prediction of CLAD. METHODS: This retrospective cohort was drawn from all consecutive adult, first LTxs performed between 2006 and 2011. Post-transplant monitoring included scheduled surveillance bronchoscopies with concurrent pulmonary-functions tests and low-dose chest CT. Quantitative density metrics (QDM) derived from CT scans obtained at the time of 10%-19% decline in forced expiratory volume in 1 second (FEV1) were evaluated: 114 bilateral LTx recipients (66 with CLAD and 48 stable) and 23 single LTx recipients (11 with CLAD, 12 stable) were included in the analysis. RESULTS: In both single and double LTx, at the time of 10%-19% drop in FEV1 from baseline, the QDM was higher in patients who developed CLAD within 3 years compared with those patients who remained stable for at least 3.5 years. The area under the receiver operating characteristic curve (AUC) was 0.89 for predicting CLAD in single LTx and 0.63 in bilateral LTx. A multipredictor AUC accounting for FEV1, QDM, presence of consolidation, and ground glass opacities increased the AUC to 0.74 in double LTx. CONCLUSIONS: QDM derived from a CT histogram at the time of early drop in FEV1 may allow prediction of CLAD in patients after single or double LTx.


Assuntos
Função Retardada do Enxerto/diagnóstico , Diagnóstico Precoce , Transplante de Pulmão/efeitos adversos , Pulmão/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Transplantados , Aloenxertos , Doença Crônica , Função Retardada do Enxerto/mortalidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ontário/epidemiologia , Prognóstico , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida/tendências
12.
Saudi J Kidney Dis Transpl ; 30(3): 640-647, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31249228

RESUMO

The outcome of long-term kidney allograft is extremely important. The present study aimed to discern the factors affecting long-term kidney allograft survival, including the type of donation and the use of extended criteria donors. Seven hundred and thirty-seven kidney transplant alone patients entered this retrospective cross-sectional study. The impact of different factors on death-censored long-term kidney allograft survival was evaluated. The Cox proportional survival model was employed to identify these factors. A value of P < 0.05 was considered statistically significant. The data were analyzed using IBM Statistical Package for the Social Sciences version 19.0. The study was conducted at the Mashhad University of Medical Sciences, Mashhad, Iran. In comparison with living kidney donations, both nontraumatic and traumatic brain death cadaveric kidney donations showed statistically significant inferior graft survival. Furthermore, the Kaplan-Meier survival analysis showed better durability of living kidney donations in comparison with traumatic and nontraumatic deceased donors (Log-rank test value = 0.001). Patients with delayed graft function (DGF) had a significantly shorter long-term death censured long-term graft survival in comparison with those without this complication. The Cox proportional models showed that DGF occurrence and the type of donation play a statistically significant role in long-term kidney graft survival. In addition, regarding graft survival, there was no difference between standard criteria and extended criteria donors. The occurrence of DGF and living or deceased types of donations have a significant effect on long-term kidney allograft survival.


Assuntos
Função Retardada do Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/uso terapêutico , Transplante de Rim/efeitos adversos , Adulto , Idoso , Estudos Transversais , Função Retardada do Enxerto/mortalidade , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/mortalidade , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim/mortalidade , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
13.
Am J Transplant ; 19(11): 3079-3086, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31062464

RESUMO

The Kidney Allocation System (KAS) has resulted in fewer pediatric kidneys being allocated to pediatric deceased donor kidney transplant (pDDKT) recipients. This had prompted concerns that post-pDDKT outcomes may worsen. To study this, we used SRTR data to compare the outcomes of 953 pre-KAS pDDKT (age <18 years) recipients (December 4, 2012-December 3, 2014) with the outcomes of 934 post-KAS pDDKT recipients (December 4, 2014-December 3, 2016). We analyzed mortality and graft loss by using Cox regression, delayed graft function (DGF) by using logistic regression, and length of stay (LOS) by using negative binomial regression. Post-KAS recipients had longer pretransplant dialysis times (median 1.26 vs 1.07 years, P = .02) and were more often cPRA 100% (2.0% vs 0.1%, P = .001). Post-KAS recipients had less graft loss than pre-KAS recipients (hazard ratio [HR]: 0.35 0.540.83 , P = .005) but no statistically significant differences in mortality (HR: 0.29 0.721.83 , P = .5), DGF (odds ratio: 0.93 1.321.93 , P = .2), and LOS (LOS ratio: 0.96 1.061.19 , P = .4). After adjusting for donor-recipient characteristics, there were no statistically significant post-KAS differences in mortality (adjusted HR: 0.37 1.042.92 , P = .9), DGF (adjusted odds ratio: 0.94 1.412.13 , P = .1), or LOS (adjusted LOS ratio: 0.93 1.041.16 , P = .5). However, post-KAS pDDKT recipients still had less graft loss (adjusted HR: 0.38 0.590.91 , P = .02). KAS has had a mixed effect on short-term posttransplant outcomes for pDDKT recipients, although our results are limited by only 2 years of posttransplant follow-up.


Assuntos
Função Retardada do Enxerto/mortalidade , Rejeição de Enxerto/mortalidade , Falência Renal Crônica/cirurgia , Transplante de Rim/mortalidade , Alocação de Recursos/estatística & dados numéricos , Doadores de Tecidos/provisão & distribuição , Obtenção de Tecidos e Órgãos/estatística & dados numéricos , Adolescente , Adulto , Criança , Morte , Função Retardada do Enxerto/etiologia , Função Retardada do Enxerto/patologia , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Masculino , Prognóstico , Fatores de Risco , Adulto Jovem
14.
Clin Transplant ; 33(5): e13536, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30869162

RESUMO

In 2012, an expert working group from the French Transplant Health Authority recommended the use of hypothermic machine perfusion (HMP) to improve kidney preservation and transplant outcomes from expanded criteria donors, deceased after brain death. This study compares HMP and cold storage (CS) effects on delayed graft function (DGF) and transplant outcomes. We identified 4,316 kidney transplants from expanded criteria donors (2011-2014) in France through the French Transplant Registry. DGF occurrence was analyzed with a logistic regression, excluding preemptive transplants. One-year graft failure was analyzed with a Cox regression. A subpopulation of 66 paired kidneys was identified: one preserved by HMP and the other by CS from the same donor. Kidneys preserved by HMP (801) vs CS (3515) were associated with more frequent recipient comorbidities and older donors and recipients. HMP had a protective effect against DGF (24% in HMP group and 38% in CS group, OR = 0.49 [0.40-0.60]). Results were similar in the paired kidneys (OR = 0.23 [0.04-0.57]). HMP use decreased risk for 1-year graft failure (HR = 0.77 [0.60-0.99]). Initial hospital stays were shorter in the HMP group (P < 0.001). Our results confirm the reduction in DGF occurrence among expanded criteria donors kidneys preserved by HMP.


Assuntos
Função Retardada do Enxerto/mortalidade , Hipotermia Induzida/métodos , Falência Renal Crônica/mortalidade , Transplante de Rim/mortalidade , Preservação de Órgãos/mortalidade , Perfusão/métodos , Doadores de Tecidos/provisão & distribuição , Idoso , Criopreservação/métodos , Função Retardada do Enxerto/etiologia , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto , Humanos , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida
15.
Kidney Int ; 95(5): 1091-1102, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30824181

RESUMO

Renal ischemia reperfusion injury (IRI) adversely affects clinical outcomes following kidney transplantation. Understanding the cellular mechanisms and the changes in gene/protein expression following IRI may help to improve these outcomes. Serum soluble fms-like tyrosine kinase 1 (sFlt-1), a circulating antiangiogenic protein, is increased in the first week following kidney transplantation. We evaluated the casual relationship of elevated sFlt-1 levels with renal microvascular dysfunction following IRI in a longitudinal study of 93 kidney transplant recipients and in several animal models. Transplant recipients with higher sFlt-1 levels had higher odds of delayed graft function, graft rejection, impaired graft function, and death. In a subgroup of 25 participants who underwent kidney biopsy within 4 months of kidney transplantation, peritubular capillary area was lower in those with elevated serum sFtl-1 levels. The administration of recombinant sFlt-1 into rodents resulted in significant structural and functional changes of the renal microvasculature, including reduced peritubular capillary density and intracapillary blood volume, and lead to increased expression of inflammatory genes and increased fibrosis. In a murine model of IRI, the kidney was a site of sFlt-1 production, and systemic neutralization of sFlt-1 preserved peritubular capillary density and alleviated renal fibrosis. Our data indicate that high sFlt-1 levels after IRI play an important role in the pathogenesis of microvascular dysfunction, thereby contributing to adverse clinical outcomes following kidney transplantation.


Assuntos
Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Traumatismo por Reperfusão/sangue , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/sangue , Adulto , Idoso , Aloenxertos/irrigação sanguínea , Aloenxertos/patologia , Animais , Biópsia , Capilares/patologia , Linhagem Celular , Estudos de Coortes , Função Retardada do Enxerto/sangue , Função Retardada do Enxerto/etiologia , Função Retardada do Enxerto/mortalidade , Modelos Animais de Doenças , Feminino , Fibrose , Rejeição de Enxerto/sangue , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/mortalidade , Humanos , Rim/irrigação sanguínea , Rim/patologia , Falência Renal Crônica/mortalidade , Estudos Longitudinais , Masculino , Camundongos , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/mortalidade , Resultado do Tratamento , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/administração & dosagem
16.
Interact Cardiovasc Thorac Surg ; 28(6): 922-928, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30726919

RESUMO

OBJECTIVES: A lung retransplant has been shown to be a valid option in selected patients with chronic lung allograft dysfunction (CLAD). However, a subgroup of patients may require, in addition to invasive mechanical ventilation, extracorporeal membrane oxygenation (ECMO) as a bridge to a retransplant. Overall and CLAD-free survival after ECMO-bridged retransplants are compared to first transplants with and without bridging ECMO and to retransplants without bridging ECMO. METHODS: We reported a retrospective, single-institution experience based on a prospective data set of all patients undergoing lung transplants between January 2004 and December 2016 with a mean follow-up of 51 ± 41 months. RESULTS: A total of 230 patients (96 men, 134 women, mean age 47.3 years) had lung transplants: 200 had first transplants without bridging ECMO; 13 had first transplants with bridging ECMO; 11 had retransplants without bridging ECMO; and 6 had retransplants with bridging ECMO. The 3- and 5-year survival rates were 81%/76%, 68%/68%, 69%/46% and 50%/25%, respectively. There was no significant difference in overall survival between those who had first transplants with and without bridging ECMO or retransplants without bridging ECMO. In contrast, patients undergoing ECMO-bridged retransplants had a significantly lower overall survival rate than those with a first transplant without bridging ECMO (P = 0.007). In addition, the post-transplant CLAD-free survival curves varied significantly among the 4 treatment groups (P = 0.041), paralleling overall survival. CONCLUSIONS: Patients requiring ECMO as a bridge to a retransplant had lower overall and CLAD-free survival rates compared to those who had a first transplant with and without bridging ECMO and a retransplant without bridging ECMO.


Assuntos
Função Retardada do Enxerto/cirurgia , Oxigenação por Membrana Extracorpórea/métodos , Transplante de Pulmão/métodos , Adolescente , Adulto , Idoso , Criança , Função Retardada do Enxerto/mortalidade , Feminino , Sobrevivência de Enxerto , Humanos , Transplante de Pulmão/mortalidade , Masculino , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Suíça/epidemiologia , Resultado do Tratamento , Adulto Jovem
17.
Transplant Proc ; 51(1): 132-135, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30661894

RESUMO

In this retrospective single-center study we evaluated the outcome after kidney transplant in recipients older than 65 years in terms of patient and graft survival and causes of death. PATIENTS AND METHODS: From 1993 to 2016, 109 consecutive first single kidney transplants in recipients older than 65 years were included. Furthermore, 2 age groups have also been identified (group A, 65-70 years old vs group B, 71-76 years old). Donor and recipient characteristics were analyzed. Other parameters were cold and warm ischemia times, delayed graft function, biopsy-proven acute rejection, and causes of death. Induction immunosuppressive therapy was performed with basiliximab or thymoglobulin. Baseline triple immunosuppression included calcineurin inhibitor, antimetabolite, and steroids. The results of preimplantation biopsies, which were performed in all expanded criteria donors were analyzed and graded according to Karpinski 2009 classification. RESULTS: Overall mortality was 39.4%: 23.2% women and 76.8% men. Causes of death were infections in 42%, tumors in 23%, cardiovascular disease in 14%, cerebrovascular disease in 7%, and unknown in 14%. The most common cause of death in men was infections (52%), and the most common cause in women was tumors (55%). At 1, 3, 5, and 10 years, overall patient survival was 89%, 84%, 72%, and 45%, and overall graft survival was 100%, 97%, 89%, and 84%, respectively. Patient and graft survival were statistically different between group A vs group B (P = .006 and P = .02, respectively). At univariate analysis significant risk factors for increased mortality were age, delayed graft function, and cold ischemia time. At multivariate analysis, delayed graft function maintained statistical significance. CONCLUSIONS: Kidney transplantation in patients older than 65 years is safe, feasible, and has good graft survival. Mortality is statistically significant in patients older than 71 years, despite a persistent low graft loss.


Assuntos
Idoso , Transplante de Rim/mortalidade , Transplante de Rim/métodos , Resultado do Tratamento , Isquemia Fria , Função Retardada do Enxerto/epidemiologia , Função Retardada do Enxerto/mortalidade , Feminino , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/mortalidade , Sobrevivência de Enxerto , Humanos , Transplante de Rim/efeitos adversos , Masculino , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos/provisão & distribuição
18.
Nephrology (Carlton) ; 24(1): 111-120, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29316017

RESUMO

AIM: Differences in early graft function between kidney transplant recipients previously managed with either haemodialysis (HD) or peritoneal dialysis are well described. However, only two single-centre studies have compared graft and patient outcomes between extended hour and conventional HD patients, with conflicting results. METHODS: This study compared the outcomes of all extended hour (≥24 h/week) and conventional HD patients transplanted in Australia and New Zealand between 2000 and 2014. The primary outcome was delayed graft function (DGF), defined in an ordinal manner as either a spontaneous fall in serum creatinine of less than 10% within 24 h, or the need for dialysis within 72 h following transplantation. Secondary outcomes included the requirement for dialysis within 72 h post-transplant, acute rejection, estimated glomerular filtration rate at 12 months, death-censored graft failure, all-cause and cardiovascular mortality, and a composite of graft failure and mortality. RESULTS: A total of 4935 HD patients (378 extended hour HD, 4557 conventional HD) received a kidney transplant during the study period. Extended hour HD was associated with an increased likelihood of DGF compared with conventional HD (adjusted proportional odds ratio 1.33; 95% confidence interval 1.06-1.67). There was no significant difference between extended hour and conventional HD in terms of any of the secondary outcomes. CONCLUSION: Compared to conventional HD, extended hour HD was associated with DGF, although long-term graft and patient outcomes were not different.


Assuntos
Função Retardada do Enxerto/etiologia , Falência Renal Crônica/terapia , Transplante de Rim/efeitos adversos , Diálise Renal/efeitos adversos , Adulto , Austrália , Biomarcadores/sangue , Doenças Cardiovasculares/etiologia , Causas de Morte , Creatinina/sangue , Função Retardada do Enxerto/mortalidade , Função Retardada do Enxerto/fisiopatologia , Função Retardada do Enxerto/terapia , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/mortalidade , Falência Renal Crônica/fisiopatologia , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Nova Zelândia , Sistema de Registros , Diálise Renal/métodos , Diálise Renal/mortalidade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
19.
Nephrol Dial Transplant ; 34(10): 1788-1798, 2019 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29955846

RESUMO

BACKGROUND: This study compared long-term outcomes of renal transplantation from donors following donation after circulatory death (DCD) with those following donation after brain death (DBD) from one of the largest centres in the UK. METHOD: Recipients of renal transplants from deceased donors between 2002 and 2014 were identified from a prospectively maintained database. Outcomes were compared between DCD (468) and DBD (905) donors and between standard criteria donors (SCDs) and extended criteria donors (ECDs). RESULTS: Graft survival (GS) and patient survival (PS) from DCD and DBD donors were comparable up to 10 years (GS: 61 versus 55%, P = 0.780; PS: 78 versus 71%, P = 0.285, respectively). Graft function was comparable after 3 months. GS and function were worse in the ECD groups, with no difference between EC-DBD and EC-DCD. PS in the ECD groups was worse than the SCD groups and PS in the EC-DCD group was worse than in the EC-DBD group. DCD donors were an independent risk factor for delayed graft function. Post-operative complications and EC-DCD donation were independent risk factors for reduced GS and PS. CONCLUSION: This study supports the use of DCD renal grafts with comparable long-term survival and function to DBD grafts. The use of EC-DCD grafts is justified in selected recipients and provides acceptable function and survival advantages over dialysis.


Assuntos
Função Retardada do Enxerto/mortalidade , Sobrevivência de Enxerto , Transplante de Rim/mortalidade , Complicações Pós-Operatórias , Doadores de Tecidos/provisão & distribuição , Coleta de Tecidos e Órgãos/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Morte , Função Retardada do Enxerto/etiologia , Circulação Extracorpórea , Feminino , Humanos , Lactente , Recém-Nascido , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
20.
Exp Clin Transplant ; 16(6): 682-689, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30295582

RESUMO

OBJECTIVES: There are conflicting reports in the literature regarding outcomes after kidney transplant for patients of black ethnicity. To investigate further, we compared outcomes for black versus white kidney transplant recipients in a single UK transplant center. MATERIALS AND METHODS: We analyzed 1066 kidney transplant recipients (80 black patients, 986 white patients) within a single-center cohort (2007-2017) in the United Kingdom, with cumulative 4446 patient-year follow-up. Data were electronically extracted from the Department of Health Informatics database for every study recruit, with manual data linkage to the UK Transplant Registry (for graft survival, delayed graft function, and rejection data) and Office for National Statistics (for mortality data). Primary outcomes of interest were graft/patient survival. RESULTS: Black recipients have increased baseline risk profiles with longer wait times, difficulty in matching, worse HLA matching, more socioeconomic deprivation, and lower rates of living kidney donors. Postoperatively, black versus white recipients had increased risk for delayed graft function (34.3% vs 10.2%; P < .001), increased 1-year rejection (16.7% vs 7.3%; P = .012), higher 1-year creatinine levels (166 vs 138 mmol/L; P = .003), and longer posttransplant length of stay (14.5 vs 9.5 days; P = .020). Although black recipients did not have increased risk of death versus white recipients (10.0% vs 11.0%, respectively; P = .486), they did have increased risk for death-censored graft loss (23.8% vs 11.1%; P = .002). However, in an adjusted Cox regression model, black ethnicity was not associated with increased risk for death-censored graft loss (hazard ratio of 1.209, 95% confidence interval, 0.660-2.216; P = .539). CONCLUSIONS: Black kidney transplant recipients in the United Kingdom have increased risk of adverse graft-related outcomes due to high-risk baseline variables rather than their black ethnicity per se.


Assuntos
População Negra , Função Retardada do Enxerto/etnologia , Rejeição de Enxerto/etnologia , Sobrevivência de Enxerto , Transplante de Rim/efeitos adversos , População Branca , Adulto , Bases de Dados Factuais , Função Retardada do Enxerto/diagnóstico , Função Retardada do Enxerto/mortalidade , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/mortalidade , Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde/etnologia , Humanos , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Determinantes Sociais da Saúde/etnologia , Fatores de Tempo , Resultado do Tratamento , Reino Unido/epidemiologia
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