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1.
Clin Nephrol ; 102: 39-50, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38699983

RESUMO

BACKGROUND AND OBJECTIVES: The relative safety and efficacy of early steroid withdrawal in kidney transplant patients after basiliximab compared to anti-thymocyte globulin (ATG) induction therapy is unknown. We aimed to compare kidney allograft outcomes in steroid use versus steroid discontinuation after basiliximab and ATG induction from the United Network for Organ Sharing (UNOS) database. MATERIALS AND METHODS: We conducted a retrospective cohort analysis of the UNOS database and included first kidney transplant recipients who received ATG or basiliximab induction therapy. We compared graft and patient outcomes in those who received steroid maintenance and those who were discharged off steroids. RESULTS: Of 106,061 patients, 25,344 (86.7%) received basiliximab induction and were maintained on steroids (B-Sm), and 3,880 (13.3%) were on a steroid-free regimen (B-Sf). Graft failure rate was significantly higher in the B-Sf compared to B-Sm at 1-year (4.1 vs. 1.8%, p < 0.001), 3-year (6.0 vs. 4.3%, p < 0.001) and 5-year follow-up (7.7 vs. 6.4%, p = 0.0004). The mortality rate was significantly higher in B-Sf at 1-year (3.3 vs. 2.4%, p = 0.0005), 3-year (7.6 vs. 5.5%, p < 0.001) and 5-year follow-up (11.5 vs. 8.8%, p < 0.001) when compared to the B-Sm. 76,837 recipients received ATG induction therapy, 51,745 (72.4%) were on steroid maintenance therapy (A-Sm) and 25,092 (32.6%) were on a steroid-free regimen (A-Sf). The graft failure rate was significantly higher in A-Sf compared to A-Sm at 1-year follow-up (2.6 vs. 2.3%, p = 0.0006), however, there was no difference at 3-year (5.0 vs. 5.0%, p = 0.53) or 5-year follow-up (7.2 vs. 8.1%, p = 0.17). There was no difference in mortality rates between A-Sf vs. A-Sm at 1 year (2.5 vs. 2.4%, p = 0.98) and at 3 years (5.5 vs. 5.4%, p = 0.45), respectively. CONCLUSION: Patients who were maintained on steroids after basiliximab induction had better 5-year allograft survival and patient survival compared to those who were not maintained on steroids. However, steroid maintenance conferred no additional benefit after ATG induction and was associated with higher mortality.


Assuntos
Soro Antilinfocitário , Basiliximab , Rejeição de Enxerto , Sobrevivência de Enxerto , Imunossupressores , Transplante de Rim , Humanos , Basiliximab/uso terapêutico , Basiliximab/administração & dosagem , Masculino , Estudos Retrospectivos , Soro Antilinfocitário/uso terapêutico , Soro Antilinfocitário/administração & dosagem , Feminino , Pessoa de Meia-Idade , Imunossupressores/uso terapêutico , Imunossupressores/administração & dosagem , Adulto , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Bases de Dados Factuais , Proteínas Recombinantes de Fusão/administração & dosagem , Proteínas Recombinantes de Fusão/uso terapêutico , Resultado do Tratamento , Esteroides/administração & dosagem , Esteroides/uso terapêutico , Aloenxertos , Fatores de Tempo
2.
Hum Immunol ; 85(3): 110787, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38480040

RESUMO

INTRODUCTION: Intestinal transplantation poses a unique challenge in the field of solid organ transplantation. The combination of tacrolimus and prednisone stands as the foundational cornerstone of maintenance immunosuppression in the field of intestinal transplantation. This case series aims to describe 1-year clinical outcomes of 5 intestinal transplant recipients who received a novel immunosuppression regimen consisting of monthly basiliximab, sublingual tacrolimus, and prednisone. METHODS: A retrospective analysis of patients who underwent intestinal transplantation in our center between January 01, 2020, and January 31, 2022, was conducted. Each recipient was followed for at least 1-year post-transplant. Recipient baseline demographics, clinical characteristics, and follow-up data were obtained from the electronic health records. Data collection included recipient demographics (age, sex, race/ethnicity, BMI), cause of intestinal failure, immunological data, infectiology data and treatment information. RESULTS: A total of five patients underwent intestinal transplantation, of which two males (40 %) and three females (60 %), with a median age of 20.1 years (17.4-28.8). The median (IQR) tacrolimus trough by month 1 was 10.4 (8.4-13.2) ng/mL. Subsequently, the median (IQR) tacrolimus troughs at specified periods are as follows, respectively: month 3: 10.2 (8.2-13.2) ng/mL; month 6: 8.4 (7.6-9.6) ng/mL; and month 12: 8.8 (6.2-9.8) ng/mL. Three patients (60.0 %) had biopsy proven rejection, but all of them had resolution after the optimization of immunosuppression. All patients were alive and had a functioning intestinal allograft at 1-year. CONCLUSION: The combination of monthly basiliximab, sublingual tacrolimus, and prednisone is an effective novel maintenance immunosuppression in intestinal transplantation. A larger and more extended study duration would be necessary to thoroughly assess the safety and sustained benefits of the novel maintenance immunosuppression regimen.


Assuntos
Basiliximab , Rejeição de Enxerto , Imunossupressores , Prednisona , Tacrolimo , Humanos , Tacrolimo/administração & dosagem , Tacrolimo/uso terapêutico , Basiliximab/administração & dosagem , Basiliximab/uso terapêutico , Masculino , Feminino , Prednisona/uso terapêutico , Prednisona/administração & dosagem , Adulto , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Estudos Retrospectivos , Rejeição de Enxerto/prevenção & controle , Rejeição de Enxerto/imunologia , Adulto Jovem , Adolescente , Resultado do Tratamento , Intestinos/transplante , Intestinos/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Transplantados , Transplante de Órgãos , Quimioterapia Combinada
3.
Transplant Proc ; 53(5): 1541-1547, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34074467

RESUMO

BACKGROUND: Acute kidney injury (AKI) is common after liver transplantation (LT). Induction with interleukin-2 receptor antagonists is often used as a "renal-sparing" strategy. The aim of this study was to assess this approach in a real-world setting in an LT center. METHODS: A retrospective cohort analysis of LTs between 2011 and 2018 was performed to assess the impact of a renal-sparing strategy using basiliximab in conjunction with mycophenolate mofetil and corticosteroids from day 0 post-LT along with delayed introduction of tacrolimus. This was compared with a group receiving tacrolimus, mycophenolate mofetil, and corticosteroids from the outset. RESULTS: The renal-sparing regimen was associated with significantly lower incidence of all-stage AKI at day 7 post-LT (36% vs 55%, P = .006) and less decline in renal function at 3 months (39% vs 57%, P = .01). No further significant differences in renal outcomes were observed at other time points on follow-up to 1 year post-LT. There was no significant difference in the incidence of acute cellular rejection, inpatient length of stay or graft survival. The decision to adopt a renal-sparing regimen was predominantly made on a clinically reactive basis within the first 24 hours post-LT in 77%, and was preordained in 23%. Cost-effectiveness analysis did not find evidence of a significant cost saving when using a renal-sparing strategy. CONCLUSION: This study provides real-world analysis of the use of a renal-sparing immunosuppression regimen in LT. Although improvements in incidence of AKI in the short term were demonstrated, this did not translate to cost savings or improved renal outcomes after 3 months.


Assuntos
Injúria Renal Aguda/prevenção & controle , Basiliximab/administração & dosagem , Imunossupressores/administração & dosagem , Complicações Pós-Operatórias/prevenção & controle , Tacrolimo/administração & dosagem , Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Corticosteroides/administração & dosagem , Adulto , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Terapia de Imunossupressão/métodos , Incidência , Rim/efeitos dos fármacos , Transplante de Fígado/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Prospectivos , Estudos Retrospectivos , Resultado do Tratamento
4.
Sci Rep ; 11(1): 827, 2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436905

RESUMO

CD25, the alpha chain of the IL-2 receptor, is expressed on activated effector T cells that mediate immune graft damage. Induction immunosuppression is commonly used in solid organ transplantation and can include antibodies blocking CD25. However, regulatory T cells (Tregs) also rely on CD25 for their proliferation, survival, and regulatory function. Therefore, CD25-blockade may compromise Treg protective role against rejection. We analysed in vitro the effect of basiliximab (BXM) on the viability, phenotype, proliferation and cytokine production of Treg cells. We also evaluated in vivo the effect of BXM on Treg in thymectomized heart transplant children receiving BXM in comparison to patients not receiving induction therapy. Our results show that BXM reduces Treg counts and function in vitro by affecting their proliferation, Foxp3 expression, and IL-10 secretion capacity. In pediatric heart-transplant patients, we observed decreased Treg counts and a diminished Treg/Teff ratio in BXM-treated patients up to 6-month after treatment, recovering baseline values at the end of the 12-month follow up period. These results reveal that the use of BXM could produce detrimental effects on Tregs, and support the evidence suggesting that BXM induction could impair the protective role of Tregs in the period of highest incidence of acute graft rejection.


Assuntos
Basiliximab/efeitos adversos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Rejeição de Enxerto/induzido quimicamente , Rejeição de Enxerto/imunologia , Transplante de Coração , Subunidade alfa de Receptor de Interleucina-2/antagonistas & inibidores , Linfócitos T Reguladores/imunologia , Basiliximab/administração & dosagem , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Criança , Pré-Escolar , Citocinas/sangue , Feminino , Fatores de Transcrição Forkhead/metabolismo , Rejeição de Enxerto/metabolismo , Rejeição de Enxerto/patologia , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Lactente , Leucócitos Mononucleares , Masculino , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo
5.
Transplant Proc ; 53(3): 1005-1009, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32178925

RESUMO

CONTEXT: Thymoglobulin is used effectively as induction agent in kidney transplantation but the optimal dose is not well established. OBJECTIVE: Demonstrate that low-dose thymoglobulin (3 mg/kg) has similar efficacy and safety compared to basiliximab induction in low-risk kidney transplantation under standard maintenance immunosuppression DESIGN, SETTING, PARTICIPANTS: Prospective randomized study in kidney transplant patients (12/2016-05/2018). INCLUSION CRITERIA: Recipients > 18 years, first living donor transplant. EXCLUSION CRITERIA: Second and multiorgan transplant, ABO incompatibility, positive cross-match, panel reactive antibodies (PRA) > 30%, positive donor-specific antibody, human immunodeficiency virus, hepatitis B surface antigen, hepatitis C virus positive, white blood cells < 2000 cells/mm3, platelets < 75,000 cells/mm3 and malignancy. INTERVENTION: Group A: basiliximab (20 mg D0 and D4). Group B: thymoglobulin (3 mg/kg total). Maintenance immunosuppression: tacrolimus, mycophenolate mofetil, and steroids. MAIN OUTCOME MEASURES: Biopsy-proven acute rejection (BPAR), delayed graft function, slow graft function, leukopenia, infections, adverse events, graft loss, estimated glomerular filtration rate, and death within 12 months. RESULTS: 100 patients (basiliximab, n = 53) (thymoglobulin, n = 47) were included. Donor and recipient characteristics were similar except for longer dialysis (basiliximab), PRA class I (1.2% basiliximab, 4.5% thymoglobulin), HLA match (basiliximab 2.8, thymoglobulin 2.2), and cytomegalovirus status. BPAR rate was basiliximab 3.8% and thymoglobulin 6.4% (P = ns). Delayed graft function (basiliximab 3.8%; thymoglobulin 4.3%), slow graft function, and 12-month leukopenia (basiliximab 11.3%, thymoglobulin 21.3%) were similar between groups (P = ns). There was no difference in infections and adverse events between groups. Patient and graft survival were as follows: basiliximab 98.1% and 92.5%, thymoglobulin 100% and 93.6% (P = ns). CONCLUSION: Low-dose thymoglobulin induction (3 mg/kg) can be used effectively and safely in low-risk kidney transplantation with good results during the first year post-transplant.


Assuntos
Soro Antilinfocitário/uso terapêutico , Basiliximab/administração & dosagem , Rejeição de Enxerto/prevenção & controle , Terapia de Imunossupressão/métodos , Imunossupressores/uso terapêutico , Adulto , Feminino , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Transplante de Rim/efeitos adversos , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplantados
6.
J Card Surg ; 35(11): 3053-3061, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33016378

RESUMO

BACKGROUND: Institutional factors have been shown to impact outcomes following orthotopic heart transplantation (OHT). This study evaluated center variability in the utilization of induction therapy for OHT and its implications on clinical outcomes. METHODS: Adult OHT patients between 2010 and 2018 were identified from the United Network for Organ Sharing registry. Transplant centers were stratified based on their rates of induction therapy utilization. Mixed-effects logistic regression models were created with drug-treated rejection within 1 year as primary endpoint and individual centers as a random parameter. Risk-adjusted Cox regression was used to evaluate patient-level mortality outcomes. RESULTS: In 17,524 OHTs performed at 100 centers, induction therapy was utilized in 48.6% (n = 8411) with substantial variability between centers (interquartile range, 21.4%-79.1%). There were 36, 30, and 34 centers in the low (<29%), intermediate (29%-66%), and high (>67%) induction utilization terciles groups, respectively. Induction therapy did not account for the observed variability in the treated rejection rate at 1 year among centers after adjusting for donor and recipient factors (p = .20). No differences were observed in postoperative outcomes among induction utilization centers groups (all, p > .05). Furthermore, there was a weak correlation between the percentage of induction therapy utilization at the center-level and recipients found to have moderate (r = .03) or high (r = .04) baseline risks for acute rejection at 1 year. CONCLUSIONS: This analysis demonstrates that there is substantial variability in the use of induction therapy among OHT centers. In addition, there was a minimal correlation with baseline recipient risk or 1-year rejection rates, suggesting a need for better-standardized practices for induction therapy use in OHT.


Assuntos
Uso de Medicamentos/estatística & dados numéricos , Rejeição de Enxerto/prevenção & controle , Transplante de Coração , Terapia de Imunossupressão/métodos , Terapia de Imunossupressão/estatística & dados numéricos , Quimioterapia de Indução/estatística & dados numéricos , Adulto , Idoso , Soro Antilinfocitário/administração & dosagem , Basiliximab/administração & dosagem , Feminino , Rejeição de Enxerto/etiologia , Transplante de Coração/efeitos adversos , Transplante de Coração/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Resultado do Tratamento
7.
Transplant Proc ; 52(6): 1709-1714, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32448669

RESUMO

The aim of induction therapy in the management of kidney transplant is to reduce the incidence of acute rejection and delayed graft function after kidney transplant. The agent for induction therapy differs depending on the recipient risks. The regimen can be either polyclonal (rabbit antithymocyte globulin [rATG]) or monoclonal antibody (basiliximab). Basiliximab is commonly used in patients with low immunologic risk. However, to date we know that the use of rATG on T cell depletion is dose dependent and more potent antirejection therapy. Therefore, we would like to look at 1-year graft function of very low-dose rATG in low immunologic risk recipients. All low immunologic risk patients who received low-dose rATG (0.5 mg/kg of body weight daily) during transplant (day 0) and on days 1 and 2 were recruited. Their renal function, HLA donor-specific antibodies, lymphocyte counts, protocol biopsy results, and cytomegalovirus (CMV) polymerase chain reaction were monitored as per clinical practice. All 10 patients had immediate graft function. Low-dose rATG caused lymphocyte counts to deplete immediately on day 0, and the effect lasted about 1 month post-transplant. All the patients had stable graft function without any significance episode of rejection. Only one patient had de novo HLA-DQ antibody. It is good to know that without prophylaxis antiviral in CMV+ donor to CMV+ recipient, the incidence of CMV viremia is considerably low in our cohort. Very low-dose rATG is an effective induction immunosuppression in low immunologic risk patients with acceptable infection risk.


Assuntos
Soro Antilinfocitário/administração & dosagem , Rejeição de Enxerto/prevenção & controle , Terapia de Imunossupressão/métodos , Imunossupressores/administração & dosagem , Transplante de Rim/efeitos adversos , Adulto , Basiliximab/administração & dosagem , Biópsia , Estudos de Coortes , Feminino , Rejeição de Enxerto/imunologia , Humanos , Infecções/induzido quimicamente , Infecções/epidemiologia , Infecções/virologia , Rim/imunologia , Transplante de Rim/métodos , Doadores Vivos , Depleção Linfocítica/métodos , Linfócitos/imunologia , Masculino , Pessoa de Meia-Idade , Centros de Atenção Terciária , Transplantes/imunologia , Resultado do Tratamento
8.
Transplant Proc ; 52(6): 1705-1708, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32444132

RESUMO

OBJECTIVES: Corticosteroids remain an important component of immunosuppressive regimens in high-risk kidney transplants. In this study, we investigated the efficacy of early steroid withdrawal with basiliximab and rituximab in ABO-blood type incompatible (ABO-i) recipients of kidney transplants. METHODS: Between 2008 and 2019, 15 patients underwent ABO-i kidney transplantation. Seven of the 15 patients were treated with a steroid maintenance protocol and the remaining 8 with an early steroid withdrawal protocol. The immunosuppressive protocol consisted of tacrolimus, mycophenolate mofetil, and methylprednisolone (MP), with basiliximab administered as induction therapy. Rituximab was administered as a single 200-mg dose 1 to 4 weeks before kidney transplantation. Two to 4 sessions of either double-filtration plasmapheresis or regular plasmapheresis or both were performed to remove anti-AB antibodies before transplantation. During surgery, MP was administered at a dose of 500 mg; thereafter, the dosage was tapered rapidly, and the drug was discontinued on day 14 post transplant. RESULTS: In the steroid maintenance group, 2 patients experienced acute antibody-mediated rejection (AMR). One patient with severe AMR had graft loss on postoperative day 4. Patient and graft survival rates in the steroid maintenance group were 100% and 86%, respectively. MP was successfully withdrawn in the steroid withdrawal group. In this group, there was no biopsy-proven rejection. Patient and graft survival rates were 100%, and when last measured, serum creatinine level ± SD was 1.6 ± 0.8 mg/dL. CONCLUSIONS: Our protocol successfully enabled the early withdrawal of steroids in recipients of ABO-i grafts; however, further follow-up is necessary to confirm our results.


Assuntos
Corticosteroides/administração & dosagem , Basiliximab/administração & dosagem , Incompatibilidade de Grupos Sanguíneos/tratamento farmacológico , Fatores Imunológicos/administração & dosagem , Rituximab/administração & dosagem , Sistema ABO de Grupos Sanguíneos/imunologia , Adulto , Incompatibilidade de Grupos Sanguíneos/cirurgia , Tipagem e Reações Cruzadas Sanguíneas , Feminino , Rejeição de Enxerto/imunologia , Humanos , Rim/imunologia , Transplante de Rim/efeitos adversos , Masculino , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Plasmaferese , Tacrolimo/administração & dosagem , Transplantes/imunologia , Resultado do Tratamento , Suspensão de Tratamento
9.
BMC Nephrol ; 21(1): 92, 2020 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-32160893

RESUMO

BACKGROUND: The efficacy and safety of minimisation of immunosuppression including early steroid withdrawal in kidney transplant recipients treated with Basiliximab induction remains unclear. METHODS: This retrospective cohort study reports the outcomes from 298 consecutive renal transplants performed since 1st July 2010-June 2013 treated with Basiliximab induction and early steroid withdrawal in low immunological risk patients using a simple immunological risk stratification and 3-month protocol biopsy to optimise therapy. The cohort comprised 225 low-risk patients (first transplant or HLA antibody calculated reaction frequency (CRF ≤50% with no donor specific HLA antibodies) who underwent basiliximab induction, steroid withdrawal on day 7 and maintenance with tacrolimus and mycophenolate mofetil (MMF), and 73 high-risk patients who received tacrolimus, MMF and prednisolone for the first 3 months followed by long term maintenance immunosuppression with tacrolimus and prednisolone. High-risk patients not undergoing 3-month protocol biopsy were continued on triple immunosuppression. RESULTS: Steroid withdrawal could be safely achieved in low immunological risk recipients with IL2 receptor antibody induction. The incidence of biopsy-proven acute rejection was 15.1% in the low-risk and 13.9% in the high-risk group (including sub-clinical rejection detected at protocol biopsy). One- year graft survival was 93.3% and patient survival 98.5% in the low-risk group, and 97.3 and 100% respectively in the high-risk group. Graft function was similar in each group at 1 year (mean eGFR 61.2 ± 23.4 mL/min low-risk and 64.6 ± 19.2 mL/min high-risk). CONCLUSIONS: Immunosuppression regimen comprising basiliximab induction, tacrolimus, MMF and prednisolone with early steroid withdrawal in low risk patients and MMF withdrawal in high risk patients following a normal 3-month protocol biopsy is effective in limiting acute rejection episodes and produces excellent rates of patient survival, graft function and complications.


Assuntos
Imunossupressores/administração & dosagem , Transplante de Rim , Cuidados Pós-Operatórios/métodos , Adulto , Idoso , Azatioprina/administração & dosagem , Basiliximab/administração & dosagem , Basiliximab/efeitos adversos , Esquema de Medicação , Feminino , Glucocorticoides/administração & dosagem , Rejeição de Enxerto/imunologia , Sobrevivência de Enxerto/imunologia , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Infecções Oportunistas/diagnóstico , Complicações Pós-Operatórias/diagnóstico , Prednisolona/administração & dosagem , Receptores de Interleucina-2/antagonistas & inibidores , Insuficiência Renal Crônica/cirurgia , Estudos Retrospectivos , Medição de Risco , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Adulto Jovem
10.
Transplant Proc ; 52(2): 556-558, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32035673

RESUMO

BACKGROUND: Calcineurin inhibitors have been implicated in acute and chronic kidney disease after liver transplant (LT). Everolimus (EVR) is a mammalian target of rapamycin inhibitor efficacious in preventing acute cellular rejection while preserving renal function among LT recipients. We evaluated the benefits on renal function of EVR immunosuppression in LT recipients. METHODS: We performed a retrospective and observational study in 477 LT recipients in Virgen de las Nieves Hospital from 2002 to 2019 on the use of EVR with tacrolimus minimization or withdrawal in LT recipients with renal dysfunction. The study included 100 patients starting EVR (20.96%); in 66 (66%) the indication was renal dysfunction. The change in renal function was assessed by estimated glomerular filtration rate. Statistical analyses were performed using SPSS 17.0 software (IBM, Munich, Germany). RESULTS: Fifty 8 patients received mycophenolate mofetil (87.8%), and tacrolimus therapy was stopped in 27 patients (40.9%). Induction therapy with basiliximab was administered in 41 patients (62.12%). There was significant difference between estimated glomerular filtration rate at the time of starting EVR and the first month at last follow-up (49.42 mL/min/1.73 m2 vs 75.27 mL/min/1.73 m2; P < .001) and at end of follow-up (24 months) (49.42 mL/min/1.73 m2 vs 64.32 mL/min/1.73 m2; P = .001). The rate of incidence of adverse events was 48.48% (32/66). Seven patients died during follow-up (10.6%), but there were no EVR-related deaths. Eleven patients (16.6%) developed biopsy-proven acute rejection. CONCLUSION: This study showed that EVR is associated with a beneficial effect on glomerular filtration rate in both the short and long term in LT recipients.


Assuntos
Everolimo/administração & dosagem , Imunossupressores/administração & dosagem , Transplante de Fígado/efeitos adversos , Complicações Pós-Operatórias/tratamento farmacológico , Insuficiência Renal Crônica/tratamento farmacológico , Adulto , Basiliximab/administração & dosagem , Biópsia , Inibidores de Calcineurina/efeitos adversos , Quimioterapia Combinada , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Terapia de Imunossupressão/métodos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Complicações Pós-Operatórias/induzido quimicamente , Insuficiência Renal Crônica/induzido quimicamente , Estudos Retrospectivos , Sirolimo/administração & dosagem , Tacrolimo/administração & dosagem
11.
Transplantation ; 104(3): 613-622, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31283665

RESUMO

BACKGROUND: In nonimmunized patients, similar rejection rates are observed for patients who have undergone thymoglobulin (antithymocyte globulins [ATG]) or basiliximab (BSX) therapy. While ATG may improve delayed graft function, it may also be associated with higher infection rates and malignancy risk. We compared survival and clinical outcomes in elderly recipients with low immunological risk according to their induction therapy. METHODS: We conducted a multicentric study on nonimmunized patients ≥65 years of age receiving a first kidney transplant between 2010 and 2017. The principal outcome was patient and graft survival. Secondary outcomes were cumulative probabilities of infection, first acute rejection episode, malignancy, de novo donor specific antibody, posttransplant diabetes (PTD), cardiac complications, estimated glomerular filtration rate, and occurrence of delayed graft function. Cox, logistic, or linear statistical models were used depending on the outcome studied, and models were weighted on the propensity scores. RESULTS: Two hundred and four patients were included in the BSX group and 179 in the ATG group with the average age of 71.0 and 70.5 years, respectively. Patient and graft survival at 3 years posttransplantation were 74% (95% CI, 65%-84%) and 68% (95% CI, 60%-78%) in ATG and BSX group, respectively, without significant difference. Occurrence of PTD was significatively higher in BSX group (23% versus 15%, P = 0.04) due to higher trough levels of Tacrolimus on month 3 (9.48 versus 7.30 ng/mL, P = 0.023). There was no difference in other evaluated outcomes. CONCLUSIONS: In elderly recipients, ATG does not lead to poorer outcomes compared with BSX and could permit lower trough levels of Tacrolimus, thus reducing occurrence of PTD.


Assuntos
Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto/imunologia , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Condicionamento Pré-Transplante/efeitos adversos , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Soro Antilinfocitário/administração & dosagem , Soro Antilinfocitário/efeitos adversos , Basiliximab/administração & dosagem , Basiliximab/efeitos adversos , Função Retardada do Enxerto/epidemiologia , Função Retardada do Enxerto/imunologia , Função Retardada do Enxerto/prevenção & controle , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/imunologia , Feminino , Seguimentos , Taxa de Filtração Glomerular , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Humanos , Terapia de Imunossupressão/efeitos adversos , Terapia de Imunossupressão/métodos , Imunossupressores/administração & dosagem , Transplante de Rim/métodos , Masculino , Complicações Pós-Operatórias/imunologia , Estudos Prospectivos , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Condicionamento Pré-Transplante/métodos , Resultado do Tratamento
12.
Pharmacotherapy ; 40(1): 26-32, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31742732

RESUMO

STUDY OBJECTIVE: Basiliximab is an immunosuppressive monoclonal antibody used for rejection prevention following solid organ transplantation; the pharmacokinetics (PK) of basiliximab in this setting are known. Basiliximab may also be used for prophylaxis and treatment of graft-versus-host disease (GVHD) in patients undergoing allogeneic hematopoietic cell transplantation (HCT); however, the PK of basiliximab in this setting are not known. Clinical transplant providers expect variation in the volume of distribution and clearance after nonmyeloablative allogeneic transplantation (NMAT) compared with solid organ transplantation. Blood loss, organ site-specific antibody accumulation, and differences in blood product use during the two transplantation approaches may generate differences in basiliximab PK. Therefore, the objective of this study was to describe the PK of basiliximab after its addition to a minimally intense NMAT regimen, in conjunction with cyclosporine, for GVHD prophylaxis in patients with hematologic malignancies. DESIGN: Population PK analysis of a single-center, single-arm, phase II clinical trial. SETTING: Academic cancer research center. PATIENTS: Fourteen adults with hematologic malignancies (acute myeloid leukemia, acute lymphoblastic leukemia, chronic lymphocytic leukemia, myelodysplastic syndrome, non-Hodgkin's lymphoma, Hodgkin's lymphoma, myelofibrosis, or severe aplastic anemia) and undergoing NMAT with a fully HLA-matched (10 of 10 antigen matched) related or unrelated donor. MEASUREMENTS AND MAIN RESULTS: Basiliximab was used in conjunction with cyclosporine to deplete activated T cells in vivo as GVHD prophylaxis. We developed a novel competitive enzyme-linked immunosorbent assay (ELISA) method using recombinant interleukin-2 receptor alpha-chain (IL-2Ra) and a commercially available soluble sIL-2R ELISA kit to permit the quantification of serum basiliximab concentrations and characterization of the PK properties of the drug in this patient population. Using a nonlinear mixed effects model with NONMEM software, a one-compartment model with first-order elimination best described the PK, as covariate analysis using stepwise covariate modeling did not improve the base model. CONCLUSION: We suggest a one-compartment population model with first-order elimination to capture the PK profile for basiliximab for this patient population.


Assuntos
Basiliximab/farmacocinética , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/farmacocinética , Adulto , Basiliximab/administração & dosagem , Ciclofosfamida/administração & dosagem , Quimioterapia Combinada , Ensaio de Imunoadsorção Enzimática , Feminino , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/terapia , Humanos , Imunossupressores/administração & dosagem , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados
13.
Int Immunopharmacol ; 76: 105881, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31520989

RESUMO

The association between immunosuppressive therapy or cytomegalovirus (CMV) infection and detection of de novo donor-specific antibody (dnDSA) at 1 year after transplantation was evaluated. The impact of dnDSA positivity at 1 year after transplantation on long-term death-censored renal graft survival was also evaluated. One hundred and sixty adults receiving living renal allografts were studied. Inclusion criteria were renal graft survival for at least 1 year and a standard regimen of immunosuppressive therapy with tacrolimus, mycophenolate mofetil (MMF), steroids, and basiliximab. DSA were measured retrospectively by the Luminex assay. The coefficient of variation (CV) was calculated and receiver operating characteristic (ROC) analysis was employed to clarify the association of tacrolimus with development of dnDSA. Seven of the 160 patients (4.4%) were positive for dnDSA. The intra-patient minimum trough level of tacrolimus (cutoff value: 3.2 ng/mL) was associated with development of dnDSA. Discontinuation of MMF and treatment of CMV infection were more frequent in patients with dnDSA than in those without dnDSA. In multivariate analysis, a low trough level of tacrolimus, discontinuation of MMF, and treatment of CMV infection within 1 year after transplantation were independently associated with detection of dnDSA at 1 year. In patients with or without dnDSA at 1 year, the 10-year allograft survival rate was 51.4 versus 87.9%, respectively (P = 0.002). A lower tacrolimus trough level, discontinuation of MMF, and treatment of CMV infection were associated with dnDSA positivity. Further investigation is needed to determine whether a new immunosuppressive regimen that avoids these factors can reduce dnDSA positivity.


Assuntos
Infecções por Citomegalovirus/imunologia , Imunossupressores/administração & dosagem , Isoanticorpos/sangue , Transplante de Rim , Adulto , Idoso , Basiliximab/administração & dosagem , Citocromo P-450 CYP3A/genética , Infecções por Citomegalovirus/genética , Feminino , Humanos , Imunossupressores/farmacocinética , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/farmacocinética , Polimorfismo Genético , Tacrolimo/administração & dosagem , Tacrolimo/farmacocinética , Adulto Jovem
14.
PLoS One ; 14(9): e0222730, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31536556

RESUMO

Early conversion to everolimus was assessed in kidney transplant recipients participating in the Eurotransplant Senior Program (ESP), a population in whom data are lacking. The SENATOR multicenter study enrolled 207 kidney transplant recipients undergoing steroid withdrawal at week 2 post-transplant (ClinicalTrials.gov [NCT00956293]). At week 7, patients were randomized (1:2 ratio) to continue the previous calcineurin inhibitor (CNI)-based regimen with mycophenolic acid (MPA) and cyclosporine or switch to a CNI-free regimen with MPA, everolimus (5-10 ng/mL) and basiliximab at weeks 7 and 12, then followed for 18 weeks to month 6 post-transplant. The primary endpoint was estimated GFR (eGFR). At week 7, 77/207 (37.2%) patients were randomized (53 everolimus, 24 control). At month 6, eGFR was comparable: 36.5±10.8ml/min with everolimus versus 42.0±13.0ml/min in the control group (p = 0.784). Discontinuation due to adverse events occurred in 27.8% of everolimus-treated patients and 0.0% of control patients (p = 0005). Efficacy profiles showed no difference. In conclusion, eGFR, safety and efficacy outcomes at month 6 post-transplant showed no difference between groups. The everolimus group experienced a higher rate of discontinuation due to adverse events. However, the high rate of non-randomization is highly relevant, indicating this to be a somewhat unstable patient population regardless of treatment.


Assuntos
Everolimo/administração & dosagem , Taxa de Filtração Glomerular/fisiologia , Rejeição de Enxerto/diagnóstico , Transplante de Rim/métodos , Idoso , Basiliximab/administração & dosagem , Inibidores de Calcineurina/administração & dosagem , Ciclosporina/administração & dosagem , Everolimo/efeitos adversos , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Rejeição de Enxerto/prevenção & controle , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Ácido Micofenólico/administração & dosagem , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Estudos Prospectivos , Fatores de Tempo
15.
Int Immunopharmacol ; 75: 105772, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31376625

RESUMO

Everolimus (EVR) is often administered with cyclosporine A (CsA), according to an established protocol. Although the administration protocol of EVR with tacrolimus (TAC) has not been established, it has been clinically demonstrated that a higher dose of EVR is necessary when used in combination with TAC than with CsA. In this study, we aimed to determine the optimal dose of EVR administered with TAC to maintain a similar EVR level in the blood to that observed when EVR is administered with CsA. Between June 2009 and January 2016, 22 patients who underwent living donor kidney transplantation were enrolled in this study. Among them, 12 patients were administered steroids, basiliximab, CsA, and EVR (CsA + EVR group) and 10 were administered steroids, basiliximab, TAC, and EVR (TAC + EVR group). Blood samples were collected at different time points from patients in both CsA + EVR and TAC + EVR groups, after drug administration. The trough EVR level in both groups was maintained within 3-8 ng/mL during the perioperative period. The optimal EVR doses for both groups were estimated by using a population pharmacokinetic analysis. Overall, the optimal dose of EVR for the TAC + EVR group was 3.59-fold higher than that for the CsA + EVR group to maintain a similar trough level to that of the latter group. Thus, administration of a higher EVR dose is recommended when provided in combination with TAC than with CsA to prevent adverse events caused by under immunosuppression, that could lead to acute kidney rejection.


Assuntos
Everolimo/administração & dosagem , Imunossupressores/administração & dosagem , Transplante de Rim , Doadores Vivos , Tacrolimo/administração & dosagem , Adulto , Basiliximab/administração & dosagem , Ciclosporina/administração & dosagem , Ciclosporina/sangue , Ciclosporina/farmacocinética , Everolimo/sangue , Everolimo/farmacocinética , Feminino , Humanos , Imunossupressores/sangue , Imunossupressores/farmacocinética , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Esteroides/administração & dosagem , Tacrolimo/sangue , Tacrolimo/farmacocinética
16.
Transplant Proc ; 51(2): 337-340, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30879536

RESUMO

INTRODUCTION: Our study compares 2 immunosuppressive strategies to reduce tacrolimus nephrotoxicity and its risk of acute tubular necrosis: delayed introduction of tacrolimus plus thymoglobulin vs initial tacrolimus plus basiliximab on the results of kidney transplant (KT) using type-III donation after circulatory death (III-DCD). MATERIAL AND METHODS: We analyzed all the transplants performed using type-III DCD in our hospital (42 cases). They were distributed in a first stage with delayed tacrolimus (3°-4° day) + thymoglobulin and a second one with initial tacrolimus + basiliximab, with a follow-up of 6 months. The rate of delayed graft function, the evolution of renal function, and the incidence of rejection were compared. RESULTS: 28 patients received thymoglobulin with delayed tacrolimus, and 13 patients received basiliximab and tacrolimus from day 0 (1 excluded). There were no significant differences in delayed graft function (27% group 1 and 23% group 2) or in rejection (10.7% and 15.4%), respectively. Serum creatinine at day 3, 7, 14, 30, and 180 showed no statistically significant differences. The levels of tacrolimus measured at 10, 30, 90, and 180 days after transplantation were similar, except for the first month: 10.10 ± 2.3 in group 1 and 12 ± 1.7 ng/mL in group 2 (P = .007). CONCLUSIONS: Delayed introduction of tacrolimus does not seem to suppose a benefit in KT using type-III DCD; therefore, the use of thymoglobulin, with its higher profile of adverse effects, seems unjustified in patients with normal immunological risk.


Assuntos
Função Retardada do Enxerto/epidemiologia , Rejeição de Enxerto/epidemiologia , Imunossupressores/administração & dosagem , Transplante de Rim/métodos , Adulto , Soro Antilinfocitário/administração & dosagem , Soro Antilinfocitário/efeitos adversos , Basiliximab/administração & dosagem , Basiliximab/efeitos adversos , Feminino , Humanos , Imunossupressores/efeitos adversos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Doadores de Tecidos
17.
Exp Clin Transplant ; 17(4): 457-460, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30066624

RESUMO

OBJECTIVES: Immunosuppressive therapy in kidney transplant recipients with hepatitis B virus infection may increase the risk of disease progression. Here, we compared outcomes of depleting (antithymocyte globulin/alemtuzumab) versus nondepleting (basiliximab/daclizumab) antibody induction in kidney transplant recipients at different serologic phases of hepatitis B virus infection. MATERIALS AND METHODS: We used the Organ Procurement and Transplantation Network/United Network for Organ Sharing database to identify adult kidney transplant recipients at different serologic phases of hepatitis B virus infection (transplants received from 2001-2011 after patients received perioperative induction with discharge on calcineurin inhibitors/mycophenolate mofetil with/without steroids). We used a Cox model to compare outcomes among patient groups. RESULTS: Median follow-up was 50.7 months (range, 28.6 to 82.6 mo). Serologic phase for the 7681 study patients were as follows: 1098 at HBsAg+/anti-HBc- (depleting = 652, nondepleting = 446), 446 at HBsAg+/anti-HBc+ (depleting = 250, nondepleting = 216), and 6117 at HBsAg-/anti-HBc+ (depleting = 3562, nondepleting = 2555) (where anti-HBc denotes hepatitis B core antibody, HBsAg denotes hepatitis B surface antigen, and +/- denote positive/negative). When we compared those with depleting versus nondepleting agents, hazard ratios (95% confidence intervals) for adjusted overall graft, death-censored graft, and patient survival were 0.97 (0.78-1.26; P = .86), 1.20 (0.83-1.60; P = .44), and 0.92 (0.66-1.30; P = .51) in the HBsAg+/anti-HBc-; 0.81 (0.55-1.18; P = .27), 0.59 (0.32-1.12; P = .11), and 0.95 (0.60-1.49; P = .83) in the HBsAg+/anti-HBc+; and 0.96 (0.86-1.05; P = .37), 0.95 (0.60-1.49; P = .97), and 0.92 (0.80-1.05; P = 0.22) in the HBsAg-/anti-HBc+ groups. CONCLUSIONS: Our study did not show adverse graft and patient outcomes associated with depleting versus nondepleting antibody induction in kidney transplant recipients at different phases of hepatitis B virus infection. This supports the selection and use of induction agents based on immunologic risk in such patients.


Assuntos
Alemtuzumab/efeitos adversos , Soro Antilinfocitário/efeitos adversos , Basiliximab/efeitos adversos , Daclizumabe/efeitos adversos , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B/virologia , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Adulto , Alemtuzumab/administração & dosagem , Soro Antilinfocitário/administração & dosagem , Basiliximab/administração & dosagem , Tomada de Decisão Clínica , Daclizumabe/administração & dosagem , Bases de Dados Factuais , Progressão da Doença , Quimioterapia Combinada , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Hepatite B/diagnóstico , Hepatite B/imunologia , Hepatite B/mortalidade , Anticorpos Anti-Hepatite B/sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/imunologia , Humanos , Imunossupressores/administração & dosagem , Transplante de Rim/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
18.
Transplant Proc ; 50(8): 2368-2370, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30316359

RESUMO

BACKGROUND: Tacrolimus is widely used in renal transplantation to help prevent acute and chronic rejection, but the nephrotoxicity of tacrolimus may compromise renal function. This study investigates the safety and efficacy in delayed initiation of tacrolimus after antilymphocyte induction therapy in kidney transplant recipients. METHODS: This retrospective cohort analysis involved data from 68 kidney transplant recipients receiving standard induction therapy (basiliximab [Simulect] or thymoglobulin) combined with tacrolimus. The patients were divided into 2 groups according to whether the start time of tacrolimus therapy was before or after 24 hours posttransplantation. Acute rejection, common complications of immunosuppression, and graft survival were compared. RESULTS: The mean (SD) timing of tacrolimus administered in the Delayed group was 4 (1.9) days after transplantation. The Delayed group patients had a higher percentage of slow graft function and delayed graft function than the No-delay group. Compared with the No-delay group, delayed initiation of tacrolimus did not increase risk of biopsy-proven acute rejection, infection, posttransplant diabetes mellitus, graft survival, and patient survival. CONCLUSIONS: Our study confirmed delayed initiation of tacrolimus after antilymphocyte induction therapy is safe and effective in renal transplant recipients with slow or delayed graft function.


Assuntos
Função Retardada do Enxerto/tratamento farmacológico , Rejeição de Enxerto/prevenção & controle , Imunossupressores/administração & dosagem , Transplante de Rim , Tacrolimo/administração & dosagem , Adulto , Soro Antilinfocitário/administração & dosagem , Basiliximab/administração & dosagem , Feminino , Sobrevivência de Enxerto/efeitos dos fármacos , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tacrolimo/efeitos adversos , Fatores de Tempo
20.
Int J Urol ; 25(2): 141-145, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29068092

RESUMO

OBJECTIVE: To evaluate the utility and safety of high-dose mizoribine combination therapy using cyclosporine and tacrolimus as calcineurin inhibitors in patients undergoing kidney transplant. METHODS: The present study enrolled 156 patients who received kidney transplants in 18 institutions between 2009 and 2013. ABO-incompatible and/or pre-sensitized recipients were excluded. Immunosuppression used cyclosporine (88) or tacrolimus (68) as a calcineurin inhibitor, and the dosage was adjusted based on blood concentrations. Mizoribine was started at 6 mg/kg/day, and the target trough level was 1-2 ng/mL. Primary efficacy end-points of this study were 2-year patient survival, 2-year graft survival and the acute rejection rate within 2 years after transplantation. RESULTS: The 2-year patient and graft survival rates in the cyclosporine group were 98.9% and 94.3%, respectively, whereas those in the tacrolimus group were 100% and 98.5%, respectively, with no significant difference between groups. Rates of onset of rejection during the observation period were also equivalent, at 22.7% in the cyclosporine group and 17.6% in the tacrolimus group. Furthermore, groups showed no significant differences in transplanted renal function. No notable differences in adverse events were observed between groups. CONCLUSIONS: A regimen of high-dose mizoribine in combination with calcineurin inhibitors basiliximab, and corticosteroids can provide effective immunosuppression while lowering the rate of cytomegalovirus infection in kidney transplant patients.


Assuntos
Rejeição de Enxerto/epidemiologia , Imunossupressores/administração & dosagem , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Ribonucleosídeos/administração & dosagem , Adulto , Basiliximab/administração & dosagem , Basiliximab/efeitos adversos , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Ciclosporina/administração & dosagem , Ciclosporina/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Feminino , Glucocorticoides/administração & dosagem , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Sobrevivência de Enxerto/imunologia , Humanos , Imunossupressores/efeitos adversos , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Ribonucleosídeos/efeitos adversos , Taxa de Sobrevida , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Resultado do Tratamento
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