RESUMO
BACKGROUND: Elderly (Eld) (≥60 years) recipients are receiving renal transplants more frequently. The pharmacokinetics (PK) studies of immunosuppressive drugs in healthy volunteers, rarely, include old patients. METHODS: We studied 208 12-hour tacrolimus (TAC) PK (0, 20, 40, 60, 90, 120, 180, 240, 360, 480, 600, 720 min) in 44 Eld (65 ± 3 years) and compared the results with 31 younger controls (Ctrl) (35 ± 6 years) recipients, taking oral TAC/mycophenolate sodium (MPS)/prednisone, at 4 different timepoints: PK1 (8 ± 2 days; n = 72), PK2 (31 ± 4 days; n = 61), PK3 (63 ± 6 days; n = 44), and PK4 (185 ± 10 days; n = 31). Tacrolimus PK was measured by ultraperformance liquid chromatography coupled to a mass spectrometer repetition and noncompartmental PKs were analyzed using Phoenix WinNonlin. RESULTS: Mean TAC dose was lower in the Eld group than in Ctrl ones throughout timepoints either by total daily dose or adjusted (Adj) per body weight. Mean TAC trough level (Cmin), used to adjust daily dose, was not different between the 2 groups in all timepoints. AdjCmax and AdjTAC-area under the curve at dosing interval were both higher in the Eld compared to the Ctrl group in PKs1, 3, and 4. Estimated total body clearance normalized by dose and weight was lower in the Eld group compared with the Ctrl in all PKs and statistically lower at PKs 1 and 3. Similar to younger recipients TAC trough level has also a high correlation (R = 0.76) with area under the curve at dosing interval. CONCLUSIONS: These data indicate that Eld recipients have a lower TAC clearance and therefore need a lower TAC dose than younger recipients.
Assuntos
Inibidores de Calcineurina/farmacocinética , Imunossupressores/farmacocinética , Transplante de Rim , Tacrolimo/farmacocinética , Adulto , Fatores Etários , Idoso , Brasil , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Inibidores de Calcineurina/sangue , Cromatografia Líquida , Cálculos da Dosagem de Medicamento , Monitoramento de Medicamentos/métodos , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/sangue , Transplante de Rim/efeitos adversos , Estudos Longitudinais , Masculino , Espectrometria de Massas , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Modelos Biológicos , Estudos Prospectivos , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Tacrolimo/sangue , Resultado do TratamentoRESUMO
BACKGROUND: Although the proportion of elderly patients among renal transplant recipients has increased, pharmacokinetic (PK) studies of immunosuppressants rarely include older patients. METHODS: We studied 12-hour everolimus (EVL) PK in 16 elderly renal transplant recipients (all whites; 10 men; mean age, 64 ± 2 years (61-71 years), in 4 separate timepoints (at 7, 30, 60, and 150 days) after EVL introduction, corresponding to a mean postrenal transplantation day: PK1 (43 ± 4 days), PK2 (65 ± 7 days), PK3 (106 ± 17 days), and PK4 (206 ± 40 days). Patients received EVL (target trough level (Ctrough, 3-8 ng/mL), prednisone, and tacrolimus (TCL) (target Ctrough, 2-5 ng/mL). RESULTS: Mean TCL-Ctrough was 7.2 ± 3.8, 4.9 ± 2.2, 4.9 ± 2.2, and 4.5 ± 1.2 ng/mL at PK1, PK2, PK3, and PK4, respectively. There were no differences among timepoints for mean EVL daily dose (data shown as PK3) (3.5 ± 1.3 mg/d), Ctrough (4.7 ± 2.5 ng/mL), AUC0-12h (106 ± 51 ng/h per mL), Caverage (8.8 ± 4.2 ng/mL), Cmax (19.2 ± 9.7 ng/mL), apparent Half-life (11.7 ± 4.2 hours), estimated total body clearance (0.39 ± 0.27 L/h), or fluctuation (166 ± 65%). Also, none of those PK parameters differed statistically when adjusted for body weight. EVL-Ctrough showed a very high correlation (r = 0.849) with AUC0-12h. CONCLUSIONS: Our data indicate that elderly renal transplant recipients starting EVL 1 month after transplantation along with a steady-state TCL level, present stable EVL-PK parameters without significant changes in dose or exposure during the first 6 months after renal transplantation.
Assuntos
Inibidores de Calcineurina/administração & dosagem , Everolimo/administração & dosagem , Everolimo/farmacocinética , Imunossupressores/administração & dosagem , Imunossupressores/farmacocinética , Transplante de Rim , Tacrolimo/administração & dosagem , Fatores Etários , Idoso , Área Sob a Curva , Brasil , Inibidores de Calcineurina/sangue , Inibidores de Calcineurina/farmacocinética , Monitoramento de Medicamentos , Quimioterapia Combinada , Everolimo/sangue , Feminino , Meia-Vida , Humanos , Imunossupressores/sangue , Estudos Longitudinais , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Modelos Biológicos , Estudos Prospectivos , Tacrolimo/sangue , Tacrolimo/farmacocinética , Resultado do TratamentoRESUMO
Equations to estimate glomerular filtration rate (eGFR) were developed in patients using the variables age, body weight, and serum creatinine, which may be different in the elderly. Elderly renal transplant patients (EG; n=70; mean age 65 ± 4 y) who measured plasma 51 Cr-EDTA-Clearance (mGFR) had mGFR compared to eGFR obtained by the Cockcroft-Gault corrected by body surface area (CG-BSA), the modification of diet in renal disease (MDRD-4), the Berlin Initiative Study (BIS-1), and the chronic kidney disease epidemiology collaboration (CKD-EPI). Results were validated using a cohort of 43, of the 70 elderly recipients, who performed a second 51 Cr-EDTA-Clearance. Mean mGFR was 47 ± 16 mL/min/1.73 m2 and statistically lower than eGFR by MDRD (52 ± 19, P=.001) and BIS-1 (51 ± 13, P=.007) but not different from the CG-BSA (47 ± 15) and CKD-EPI (49 ± 18). The CKD-EPI and CG-BSA presented the lowest bias but only CKD-EPI also showed the highest 30% and 10% accuracy. The same findings were repeated in the validation set. For a cohort of elderly recipients ≥65 years (n=35, 68 ± 3y), the CKD-EPI performed better with the lowest bias (0 ± 12 mL/min/1.73 m2 ) and best 30% and 10% accuracy. The CKD-EPI equation is a valuable tool to monitor GFR in the elderly RTx recipients.
Assuntos
Taxa de Filtração Glomerular , Indicadores Básicos de Saúde , Transplante de Rim , Cuidados Pós-Operatórios/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Análise de Regressão , Estudos RetrospectivosRESUMO
BACKGROUND: The discard rate of kidneys recovered from deceased donors with acute renal failure (ARF) is higher compared with those without ARF mainly due to the uncertainty regarding short-term and long-term outcomes. METHODS: We retrospectively analyzed 1-year patient, graft, and rejection-free survivals and renal function of transplantations performed with kidneys recovered from deceased donors with or without ARF, defined as serum creatinine level of more than 1.5 mg/dL. We performed multivariable analysis to evaluate whether ARF was an independent risk factor associated with inferior outcomes. RESULTS: Of a total of 1518 patients, 253 received kidneys from expanded-criteria donors (ECD; with ARF [n=116] and without ARF [n=137]) and 1265 from standard-criteria donors (SCD; with ARF [n=369] and without ARF [n=896]). The incidence of delayed graft function was higher in ECD (68.1% vs. 58.4%; P=0.072) and SCD (69.9% vs. 50.6%; P<0.001) recipients of kidneys with ARF compared with those without ARF, respectively. At 1 year, patient, graft, and rejection-free survivals were not statistically different in SCD or ECD recipients with or without ARF. Renal function at 1 year was similar in recipients of ECD (41.9±26.3 vs. 40.1±21.7 mL/min; P=0.565) or SCD (50.9±29.9 vs. 53.6±28.5 mL/min; P=0.131) kidneys with and without ARF, respectively. Compared with kidneys without ARF, receiving a kidney allograft with ARF was not associated with increased risk of death, graft lost, or inferior renal function 1 year after transplantation. CONCLUSION: In this cohort of patients, kidneys from deceased donors with ARF provided graft survival and renal function comparable with kidneys from donors without ARF 1 year after transplantation.
Assuntos
Injúria Renal Aguda/mortalidade , Transplante de Rim , Rim/cirurgia , Nefrectomia , Doadores de Tecidos/provisão & distribuição , Injúria Renal Aguda/fisiopatologia , Adolescente , Adulto , Biomarcadores/sangue , Distribuição de Qui-Quadrado , Creatinina/sangue , Função Retardada do Enxerto/etiologia , Feminino , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Estimativa de Kaplan-Meier , Rim/fisiopatologia , Transplante de Rim/efeitos adversos , Transplante de Rim/mortalidade , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto JovemRESUMO
O Sistema Nacional de Transplantes (SNT) brasileiro coordena e regulamenta o maior programa de transplantes público do mundo. Com o seu estabelecimento, em 1997, o número de transplantes renais aumentou de 920 (5,8 por milhão de população - pmp), em 1998, para 4.957 (26 pmp) em 2011. Existem disparidades geográficas evidentes nos desempenhos entre as cinco regiões nacionais. Estas disparidades são diretamente relacionadas à densidade populacional regional, ao produto interno bruto e ao número de médicos com treinamento em transplante. Acompanhando o desafio de atenuar as disparidades regionais no acesso ao transplante, o sistema pode ser aperfeiçoado pela criação de um registro nacional para receptores de transplante e de doadores vivos de rim, e também pela promoção de estudos clínicos e experimentais voltados a melhor compreender a resposta imune relacionada ao transplante em nossa população.
The Brazilian National Tranplant System (SNT) coordinates and regulates perhaps the largest public transplant program worldwide. Since its establishment in 1997, the number of kidney transplants increased from 920 (5.8 pmp) in 1998 to 4,957 (26 pmp) in 2011. There are clear regional disparities in performance across all national regions. These disparities are directly related to regional population density, gross domestic product, and number of tranplant physicians. Besides the challenge of reducing the regional disparities related to the access to transplantation, it can be further improved by creating a national outcome registry for transplant recipient and for living kidney donors, and also by promoting clinical and experimental studies aimed to better understand the immune response related to transplantation in our population.
Assuntos
Humanos , Masculino , Feminino , Política de Saúde , Transplante de Órgãos/tendências , Brasil , Disparidades em Assistência à Saúde , Capacitação Profissional , Programas Nacionais de Saúde/normas , Características de Residência , Obtenção de Tecidos e Órgãos , Transplante de RimRESUMO
The Brazilian National Transplantation System coordinates and regulates perhaps the largest public transplantation program worldwide. Since its implementation in 1997, the number of kidney transplantations increased from 920 (5.8 pmp) in 1998, to 4,630 (24.1 pmp) in 2010. This growth was primarily due to the increased number of effective donors (from 1.8 pmp in 1998 to 9.3 pmp in 2010), with a corresponding increased number of kidneys transplanted from deceased donors (3.8 pmp in 1999 versus 9.9 pmp in 2010).The number of kidney transplantations from living donors has not increased significantly, from 1,065 (6.7 pmp) in 1998 to 1,641 (8.6 pmp) in 2010, either as a consequence of the observed increase in the deceased donor program or perhaps because of strict government regulations allowing only transplantations from related donors. From 2000 to 2009, the mean age of living donors increased from 40 to 45 years, while it increased from 33 to 41 years for deceased donors, of whom roughly 50% die of stroke. There are clear regional disparities in transplantation performance across the national regions. While the state of São Paulo is ranked first in organ donation and recovery (22.5 pmp), some states of the Northern region have much poorer performances. These disparities are directly related to different regional population densities, gross domestic product distribution, and number of trained transplantation physicians. The initial evaluation of the centers with robust outcomes indicates no clear differences in graft survival in comparison with centers in the USA and Europe. Ethnicity and time on dialysis, but not the type of immunosuppressive regimen, decisively influence the measured outcomes. Since the implementation of national clinical research regulations in 1996, Brazilian centers have participated in a number of national and international collaborative trials for the development of immunosuppressive regimens. Besides the challenge of reducing the regional disparities related to access to transplantation, further improvements can be obtained by the creation of a national registry of the outcomes of transplanted patients and living donors, and also by the promotion of clinical and experimental studies to better understand the transplantation-related immune response of the Brazilian population.
Assuntos
Disparidades em Assistência à Saúde/estatística & dados numéricos , Transplante de Rim/estatística & dados numéricos , Adulto , Brasil , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obtenção de Tecidos e Órgãos/estatística & dados numéricosRESUMO
O Sistema Nacional de Transplantes (SNT) Brasileiro coordena e regulamenta o, provavelmente, maior programa de transplantes públicos do mundo. Desde o seu estabelecimento, em 1997, o número de transplantes renais aumentou de 920 (5,8 pmp), em 1988, para 4.630 (24,1 pmp), em 2010. Esse crescimento foi primariamente devido ao aumento no número de doadores efetivos (de 1,8 pmp em 1998 para 9,3 pmp em 2010), com aumento correspondente no número de rins transplantados de doadores falecidos (3,8 pmp em 1999 versus 9,9 pmp em 2010). O número de rins transplantados com órgãos de doadores vivos não aumentou significativamente, 1.065 (6,7 pmp), em 1998, para 1.641 (8,6 pmp), em 2010, tanto em consequência do melhor desempenho do programa de doadores falecidos, como talvez também devido a mais restrita regulamentação, permitindo apenas doação entre doadores vivos relacionados. De 2000 a 2009, a idade média dos doadores vivos aumentou de 40 para 45 anos, e a dos doadores falecidos, de 33 para 41 anos, com eventos cerebrovasculares sendo responsáveis por 50 por cento dos episódios de óbito atualmente. Existem disparidades geográficas evidentes nos desempenhos entre as 5 regiões nacionais. Enquanto o estado de São Paulo ocupa a primeira posição em doação e captação de órgãos (22,5 pmp), alguns estados da região Norte apresentam pequena ou nenhuma atividade de transplante. Essas disparidades estão diretamente relacionadas à densidade populacional regional, ao produto interno bruto e ao número de médicos com treinamento em transplante. A avaliação inicial de desfechos clínicos robustos não indica diferenças nas sobrevidas do enxerto em comparação com as observadas nos EUA e na Europa. A etnia e o tempo em diálise, mas não o tipo de imunossupressão, apresentam influência decisiva nos desfechos medidos. A regulamentação nacional da pesquisa clínica foi implementada a partir de 1996, permitindo a participação de centros brasileiros em numerosos estudos clínicos nacionais e internacionais para o desenvolvimento de regimes imunossupressores. Acompanhando o desafio de atenuar as disparidades regionais no acesso ao transplante, o sistema pode ser aperfeiçoado pela criação de um registro nacional para receptores de transplante e de doadores vivos de rins e também pela promoção de estudos clínicos e experimentais voltados a melhor compreender a resposta imune relacionada ao transplante em nossa população.
The Brazilian National Transplantation System coordinates and regulates perhaps the largest public transplantation program worldwide. Since its implementation in 1997, the number of kidney transplantations increased from 920 (5.8 pmp) in 1998, to 4,630 (24.1 pmp) in 2010. This growth was primarily due to the increased number of effective donors (from 1.8 pmp in 1998 to 9.3 pmp in 2010), with a corresponding increased number of kidneys transplanted from deceased donors (3.8 pmp in 1999 versus 9.9 pmp in 2010).The number of kidney transplantations from living donors has not increased significantly, from 1,065 (6.7 pmp) in 1998 to 1,641 (8.6 pmp) in 2010, either as a consequence of the observed increase in the deceased donor program or perhaps because of strict government regulations allowing only transplantations from related donors. From 2000 to 2009, the mean age of living donors increased from 40 to 45 years, while it increased from 33 to 41 years for deceased donors, of whom roughly 50 percent die of stroke. There are clear regional disparities in transplantation performance across the national regions. While the state of São Paulo is ranked first in organ donation and recovery (22.5 pmp), some states of the Northern region have much poorer performances. These disparities are directly related to different regional population densities, gross domestic product distribution, and number of trained transplantation physicians. The initial evaluation of the centers with robust outcomes indicates no clear differences in graft survival in comparison with centers in the USA and Europe. Ethnicity and time on dialysis, but not the type of immunosuppressive regimen, decisively influence the measured outcomes. Since the implementation of national clinical research regulations in 1996, Brazilian centers have participated in a number of national and international collaborative trials for the development of immunosuppressive regimens. Besides the challenge of reducing the regional disparities related to access to transplantation, further improvements can be obtained by the creation of a national registry of the outcomes of transplanted patients and living donors, and also by the promotion of clinical and experimental studies to better understand the transplantation-related immune response of the Brazilian population.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Disparidades em Assistência à Saúde/estatística & dados numéricos , Transplante de Rim/estatística & dados numéricos , Brasil , Obtenção de Tecidos e Órgãos/estatística & dados numéricosRESUMO
INTRODUCTION: The emergence of the pandemic outbreak of influenza A (H1N1) in April, 2009, represented a logistic challenge for public health. Although most infected patients presented clinical and evolutionary manifestations which were very similar to seasonal influenza, a significant number of individuals developed pneumonia and severe acute respiratory failure. The impact of influenza A (H1N1) in immunocompromised patients is not well established yet. METHODS: This study aimed to analyze the clinical presentations and evolution of influenza A (H1N1) in 19 kidney transplant recipients. Influenza A (H1N1) infection was confirmed by RT-PCR in all patients. Treatment included antiviral therapy with oseltamivir phosphate and antibiotics. RESULTS: The studied population was compounded mostly of white people (63%), males (79%), at a mean age of 38.6 ± 17 years and patients with at least one comorbidity (53%). Influenza A (H1N1) infection was identified 41.6 ± 49.6 months after transplantation. Common symptoms included cough (100%), fever (84%), dyspnea (79%), and myalgia (42%). Acute allograft dysfunction was observed in 42% of the patients. Five patients (26%) were admitted to the Intensive Care Unit, two (10%) required invasive ventilation support, and two (10%) required vasoactive drugs. Mortality rate was 10%. CONCLUSIONS: Acute renal allograft dysfunction was a common finding. Clinical, laboratory, and evolutionary characteristics were comparable to those in the general population.