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1.
Life Sci ; 271: 119154, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33539910

RESUMO

Ulcerative colitis (UC) is a chronic inflammatory bowel disease that increases the risk of colorectal cancer. UC is highly associated with the disturbance of the immune system leading to oxidative stress and chronic inflammation of intestine. Therefore, the current study was conducted to investigate the potential anti-oxidant and anti-inflammatory effects of MMF against acetic acid-induced UC that might be associated with the regulation of Nrf-2 and NLRP3 inflammasome signaling. UC was induced in Sprague-Dawley rats by intracolonic instillation of acetic acid. Forty-eight hours post UC induction, MMF (50 mg/kg/day, orally) was given for 8 consecutive days. Then, colon tissues and blood samples were collected. Results showed that MMF significantly attenuated the acetic acid-induced functional, biochemical, and inflammatory injuries in colon. MMF significantly decreased oxidative stress as indicated by the decreased malondialdehyde concentration and the increased total antioxidant capacity, glutathione, catalase, and superoxide dismutase concentrations in colon tissues. MMF also significantly increased Nrf-2 and decreased NLRP3 inflammasome expressions. Moreover, MMF decreased expression of interferon-gamma and increased expression of interferon-alpha. MMF also significantly decreased expression of pro-inflammatory cytokines, interleukin (IL)-1ß and IL-18. These results suggest that MMF has antioxidant and anti-inflammatory effects against acetic acid-induced UC through the upregulation of Nrf-2, and INF-α expression in addition to the suppression of NLRP3 inflammasome and subsequent release of IL1ß, IL-18 and INF-γ.


Assuntos
Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Ácido Micofenólico/administração & dosagem , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Ácido Acético/toxicidade , Animais , Colite Ulcerativa/induzido quimicamente , Inibidores Enzimáticos/administração & dosagem , Inflamassomos/antagonistas & inibidores , Inflamassomos/metabolismo , Masculino , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
2.
Arq Bras Cir Dig ; 33(4): e1551, 2021.
Artigo em Inglês, Português | MEDLINE | ID: mdl-33503111

RESUMO

BACKGROUND: Tacrolimus and mycophenolate mofetil are immunosuppressive agents widely used on the postoperative period of the transplants. AIM: To evaluate the influence of the association of them on the abdominal wall healing in rats. METHODS: Thirty-six Wistar rats were randomly assigned in three groups of 12. On the early postoperative period, four of the control group and three of the experimental groups died. The three groups were nominated as follow: control group (GC, n=8); group I (GI, n=11, standard operation, mycophenolate mofetil and tacrolimus); group II (GII, n=10, standard operation, mycophenolate mofetil and tacrolimus). The standard operation consisted of right total nephrectomy and 20 min ischemia of the left kidney followed by reperfusion. Both NaCl 0.9% and the immunosuppressive agents were administered starting on the first postoperative day and continuing daily until the day of death on the 14th day. On the day of their deaths, two strips of the anterior abdominal wall were collected and submitted to breaking strength measurement and histological examination. RESULTS: There were no significant differences in wound infection rates (p=0,175), in the breaking strength measurement and in the histological examination among the three groups. CONCLUSION: The combination of the immunosuppressive agents used in the study associated with renal ischemia and reperfusion does not interfere in the abdominal wall healing of rats.


Assuntos
Parede Abdominal/cirurgia , Imunossupressores/farmacologia , Rim/irrigação sanguínea , Ácido Micofenólico/farmacologia , Traumatismo por Reperfusão/complicações , Tacrolimo/farmacologia , Animais , Isquemia , Ácido Micofenólico/administração & dosagem , Ratos , Ratos Wistar , Reperfusão , Tacrolimo/administração & dosagem
3.
BMC Infect Dis ; 21(1): 89, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33472599

RESUMO

BACKGROUND: There are limited data on Coronavirus disease 2019 (COVID-19) in solid organ transplant patients, especially in heart transplant recipients, with only a few case reports and case series described so far. Heart transplant recipients may be at particular high risk due to their comorbidities and immunosuppressed state. CASE PRESENTATION: This report describes the clinical course and the challenging management of early COVID-19 infection in two heart transplant recipients who tested positive for the SARS-CoV-2 virus in the perioperative period of the transplant procedure. The two patients developed a severe form of the disease and ultimately died despite the initiation of an antiviral monotherapy with hydroxychloroquine coupled with the interruption of mycophenolate mofetil. CONCLUSIONS: These two cases illustrate the severity and poor prognosis of COVID-19 in the perioperative period of a heart transplant. Thorough screening of donors and recipients is mandatory, and the issue of asymptomatic carriers needs to be addressed.


Assuntos
/complicações , Transplante de Coração/efeitos adversos , Antimaláricos/uso terapêutico , Antivirais/uso terapêutico , Comorbidade , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Transplantados
4.
BMJ Case Rep ; 13(12)2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33370951

RESUMO

Non-alcoholic fatty liver disease (NAFLD) is nowadays the most common liver disease worldwide. Autoimmune hepatitis (AIH) is a relatively rare disease of the liver characterised by female predominance, circulating autoantibodies, polyclonal hypergammaglobulinaemia, interface hepatitis on histology and favourable response to immunosuppression. The possibility of an additional AIH diagnosis in patients with NAFLD (NAFLD/AIH concurrence) or the presence of AIH alone instead of a supposed NAFLD diagnosis represents a challenge for clinicians. We report herein two adult patients (a 33-year-old woman and a 59-year-old man) with a previous NAFLD diagnosis who proved finally to suffer from AIH alone. These two representative cases indicate how difficult and complicated could be sometimes the diagnosis of patients with AIH highlighting the range of disease manifestations and severity while they also underline that although NAFLD is by far the most frequent chronic liver disease this could not be always the case.


Assuntos
Anticorpos Antinucleares/sangue , Hepatite Autoimune/diagnóstico , Síndrome Metabólica/complicações , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Obesidade Mórbida/complicações , Adulto , Anticorpos Antinucleares/imunologia , Biópsia , Diagnóstico Diferencial , Erros de Diagnóstico , Técnicas de Imagem por Elasticidade , Feminino , Hepatite Autoimune/tratamento farmacológico , Hepatite Autoimune/imunologia , Hepatite Autoimune/patologia , Humanos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunossupressores/administração & dosagem , Fígado/diagnóstico por imagem , Fígado/imunologia , Fígado/patologia , Testes de Função Hepática , Masculino , Síndrome Metabólica/imunologia , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Hepatopatia Gordurosa não Alcoólica/etiologia , Obesidade Mórbida/imunologia , Prednisolona/administração & dosagem
5.
BMJ Case Rep ; 13(12)2020 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-33370992

RESUMO

We present a case of a 49-year-old woman diagnosed with aquaporin-4 antibody-positive transverse myelitis, who developed a significant transaminitis 2 months after commencing mycophenolate mofetil (MMF) as a steroid-sparing agent. No other risk factors were identified, a blood liver panel was negative and liver biopsy showed features compatible with drug-induced liver injury (DILI). MMF was stopped with a corresponding normalisation of serum alanine aminotransferase over the next 2 months. This case highlights MMF as a rare cause of DILI and provides justification for monitoring of liver biochemistry on therapy.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas/etiologia , Imunossupressores/efeitos adversos , Ácido Micofenólico/efeitos adversos , Mielite Transversa/tratamento farmacológico , Alanina Transaminase/sangue , Aquaporina 4/imunologia , Autoanticorpos/sangue , Autoanticorpos/imunologia , Biópsia , Doença Hepática Crônica Induzida por Substâncias e Drogas/sangue , Doença Hepática Crônica Induzida por Substâncias e Drogas/diagnóstico , Doença Hepática Crônica Induzida por Substâncias e Drogas/patologia , Substituição de Medicamentos , Feminino , Humanos , Imunossupressores/administração & dosagem , Fígado/efeitos dos fármacos , Fígado/patologia , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Mielite Transversa/sangue , Mielite Transversa/imunologia , Rituximab/administração & dosagem
9.
Transplantation ; 104(8): 1686-1694, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32732848

RESUMO

BACKGROUND: It is commonly believed that mTOR inhibitors (mTORi) should not be used in high-immunological risk kidney transplant recipients due to a perceived increased risk of rejection. However, almost all trials that examined the association of optimal-dose mTORi with calcineurin inhibitor (CNI) have excluded hypersensitized recipients from enrollment. METHODS: To shed light on this issue, we examined 71 consecutive patients with a baseline calculated panel reactive antibody (cPRA) ≥50% that underwent kidney transplantation from June 2013 to December 2016 in our unit. Immunosuppression was based on CNI (tacrolimus), steroids and alternatively mycophenolic acid (MPA; n = 38), or mTORi (either everolimus or sirolimus, n = 33, target trough levels 3-8 ng/mL). RESULTS: Demographic and immunological risk profiles were similar, and almost 90% of patients in both groups received induction with lymphocyte-depleting agents. Cox-regression analysis of rejection-free survival revealed better results for mTORi versus MPA in terms of biopsy-proven acute rejection (hazard ratio [confidence interval], 0.32 [0.11-0.90], P = 0.031 at univariable analysis and 0.34 [0.11-0.95], P = 0.040 at multivariable analysis). There were no differences in 1-year renal function, Banff chronicity score at 3- and 12-month protocol biopsy and development of de novo donor-specific antibodies. Tacrolimus trough levels along the first year were not different between groups (12-mo levels were 8.72 ± 2.93 and 7.85 ± 3.07 ng/mL for MPA and mTORi group respectively, P = 0.277). CONCLUSIONS: This single-center retrospective cohort analysis suggests that in hypersensitized kidney transplant recipients receiving tacrolimus-based immunosuppressive therapy similar clinical outcomes may be obtained using mTOR inhibitors compared to mycophenolate.


Assuntos
Dessensibilização Imunológica/métodos , Rejeição de Enxerto/prevenção & controle , Imunossupressores/administração & dosagem , Transplante de Rim/efeitos adversos , Serina-Treonina Quinases TOR/antagonistas & inibidores , Adulto , Idoso , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Dessensibilização Imunológica/efeitos adversos , Quimioterapia Combinada/efeitos adversos , Quimioterapia Combinada/métodos , Everolimo/administração & dosagem , Everolimo/efeitos adversos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Rejeição de Enxerto/imunologia , Antígenos HLA/imunologia , Humanos , Imunossupressores/efeitos adversos , Isoanticorpos/imunologia , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Estudos Retrospectivos , Sirolimo/administração & dosagem , Sirolimo/efeitos adversos , Serina-Treonina Quinases TOR/imunologia , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Resultado do Tratamento
10.
Transplant Proc ; 52(6): 1855-1857, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32571709

RESUMO

OBJECTIVES: Mycophenolate mofetil (MMF) is mainly used in conjunction with calcineurin inhibitors as an additional immunosuppressive for renal sparing after liver transplantation. However, few reports about MMF use in infants after living donor liver transplantation (LDLT) are available. The purpose of this study was to examine the efficacy and safety of MMF in infants. METHODS: This study enrolled infants younger than 1 year of age who received LDLT at our institution. Patients received oral MMF twice daily. The initial dose was 40 to 50 mg/kg/d, which was increased to a target mycophenolic acid (MPA) trough level of 2 mg/L. Body weight, height, MMF dose, MPA trough level, acute cellular rejection (ACR) episodes, pathologic findings, and adverse effects were analyzed. Allograft fibrosis was graded using the Meta-analysis of Histological Data in Viral Hepatitis score. RESULTS: Patients received MMF for refractory ACR (n = 2), fulminant hepatitis (n = 2), and pre-existing antibodies (n = 1). Original diseases were biliary atresia (n = 3) and fulminant hepatitis (n = 2). Mean age at transplant was 8 months (range 3-10 months). The last available mean trough level was 2.7 mg/L. The mean dose was 66 mg/kg/d or 1429 mg/m2/d at the time of the last available through level. The regression line for MMF dose and MPA trough level was y = 1.8 × 10-3x. The correlation coefficient was 0.65. All allografts showed F1 to F2 fibrosis. Two patients discontinued MMF because of infection and bone marrow suppression, respectively. Two patients converted to everolimus. One patient continued on MMF. CONCLUSIONS: After LDLT, infants require a higher MMF dose than older patients based on trough levels, but allograft fibrosis can progress.


Assuntos
Rejeição de Enxerto/prevenção & controle , Imunossupressores/administração & dosagem , Transplante de Fígado , Ácido Micofenólico/administração & dosagem , Feminino , Humanos , Imunossupressores/sangue , Lactente , Doadores Vivos , Masculino , Ácido Micofenólico/sangue , Fatores de Tempo
11.
Medicine (Baltimore) ; 99(24): e20481, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541471

RESUMO

RATIONALE: Coronavirus disease 2019 (COVID-19) is a novel infectious disease and became a global issue. Treatment of COVID-19 especially in solid organ transplant recipients is empirical and controversial, especially the adjustment of the immunosuppressants. PATIENT CONCERNS: A 29-year-old kidney transplant recipient with the symptoms of COVID-19 pneumonia. DIAGNOSES: COVID-19 pneumonia after kidney transplantation. INTERVENTIONS: He was treated with modified immunosuppressants (unchanged dose of tacrolimus and oral corticosteroids while discontinuing mycophenolate mofetil (MMF)), antibiotics, interferon α-2b inhalation and traditional Chinese medicine. OUTCOMES: He recovered from COVID-19 pneumonia after 29 days of hospitalization. And the renal function (measured as blood urea nitrogen, serum creatinine, and urine protein) returned to normal. LESSONS: In certain group of COVID-19 (e.g., mild to moderate cases, young patients without comorbidities), a reduction instead of an overall withdrawal of immunosuppressant in kidney transplant recipients is feasible.


Assuntos
Betacoronavirus , Infecções por Coronavirus/terapia , Imunossupressores/administração & dosagem , Transplante de Rim , Ácido Micofenólico/administração & dosagem , Pneumonia Viral/terapia , Adulto , Antibacterianos/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Interferon alfa-2/uso terapêutico , Masculino , Oxigenoterapia , Pandemias , Pneumonia Viral/tratamento farmacológico , Resultado do Tratamento
13.
Am J Transplant ; 20(7): 1882-1884, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32243672

RESUMO

The clinical manifestation of COVID-19 can vary from an asymptomatic course to ARDS requiring invasive mechanical ventilation and extracorporeal membrane oxygenation. A kidney transplanted patient infected with SARS CoV-2 infection showed a mild disease despite immune suppression. It is possible that Immunosuppression can "be protective" as the cytokine storm is an important factor in the disease story. Despite the good outcome reported in the present case report, is remains of vital importance the solid organ transplant patients use precautions in order to avoid the infection.


Assuntos
Infecções por Coronavirus/complicações , Infecções por Coronavirus/terapia , Glomerulonefrite por IGA/complicações , Falência Renal Crônica/complicações , Transplante de Rim , Pneumonia Viral/complicações , Pneumonia Viral/terapia , Betacoronavirus , Ceftriaxona/administração & dosagem , Citocinas/metabolismo , Glomerulonefrite por IGA/cirurgia , Humanos , Imunossupressão/efeitos adversos , Imunossupressão/métodos , Falência Renal Crônica/cirurgia , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Pandemias , Tacrolimo/administração & dosagem , Resultado do Tratamento
14.
Medicine (Baltimore) ; 99(15): e19741, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282733

RESUMO

INTRODUCTION: Immune-related adverse events (ir-AEs) are increasingly becoming a concern, as immune checkpoint inhibitors (ICIs) are used more frequently. Herein, we present a case of fulminant cytokine release syndrome (CRS) complicated by dermatomyositis after the combination therapy with ICIs. PATIENT CONCERNS: A 70-year-old male developed dermatomyositis during the course of treatment with two ICIs, nivolumab and ipilimumab. He was treated by steroid pulse therapy, but the effect was limited. Afterwards, he had acute-onset high fever, hypotension, respiratory failure, impaired consciousness, renal failure, and coagulation abnormality at the same time. C reactive protein (CRP), creatinine kinase (CK), D-dimer, and ferritin levels were considerably elevated: CRP, 24 mg/dL; CK, 40,500 U/L; D-dimer, 290 µg/mL; ferritin, 329,000 ng/mL. DIAGNOSIS: CRS induced by ICI combination therapy. INTERVENTIONS: Given that high fever and elevated CRP level indicated potential sepsis, an antibiotic was used until the confirmation of negative blood cultures. All the simultaneous acute symptoms were supposed to be CRS. He was admitted to the intensive care unit (ICU), and temporary intubation and hemodialysis were needed. Immunosuppressive therapy was reinforced by mycophenolate mofetil together with steroid, and plasma exchange was performed for the elimination of abnormal proteins. OUTCOMES: The patient's clinical symptoms and laboratory parameters gradually improved and he was discharged from the ICU in a month. CONCLUSION: Fulminant CRS can be induced by ICI combination therapy. As the initial symptoms of CRS resemble sepsis, it is important to consider CRS as a differential diagnosis and to initiate immunosuppressive therapy early when needed. In steroid-resistant cases, early introduction of other immunosuppressive therapy and plasma exchange can be effective.


Assuntos
Terapia Combinada/métodos , Síndrome da Liberação de Citocina/sangue , Síndrome da Liberação de Citocina/complicações , Dermatomiosite/etiologia , Idoso , Antibióticos Antineoplásicos/administração & dosagem , Antibióticos Antineoplásicos/uso terapêutico , Antineoplásicos Imunológicos/administração & dosagem , Antineoplásicos Imunológicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Biomarcadores/sangue , Síndrome da Liberação de Citocina/tratamento farmacológico , Dermatomiosite/sangue , Dermatomiosite/patologia , Dermatomiosite/terapia , Diagnóstico Diferencial , Humanos , Fatores Imunológicos/administração & dosagem , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Ipilimumab/administração & dosagem , Ipilimumab/efeitos adversos , Ipilimumab/uso terapêutico , Masculino , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/uso terapêutico , Nivolumabe/administração & dosagem , Nivolumabe/efeitos adversos , Nivolumabe/uso terapêutico , Troca Plasmática/métodos , Resultado do Tratamento
16.
Sci Rep ; 10(1): 6062, 2020 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-32269271

RESUMO

Immunoglobulin A nephropathy (IgAN) is a common autoimmune glomerulonephritis that can result in end-stage renal disease (ESRD). Whether immunosuppressants are superior or equivalent to supportive care is still controversial. A network meta-analysis was conducted to compare the efficacy and safety of immunosuppressive treatment for IgAN. Medline, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, and EMBASE were searched on December 30, 2018. We used a random-effects model with a Bayesian approach to appraise both renal outcomes and serious adverse effects. Relative risks (RRs) with 95% confidence intervals (CIs) were calculated to present the relative effects. The ranking probabilities were calculated by the surface under the cumulative ranking curve (SUCRA). In total, 24 RCTs comprising 6 interventions were analyzed. Steroids significantly delayed the progression of renal deterioration with acceptable serious adverse effects, compared with supportive care (RR = 0.28, 95% CI = 0.13-0.51, SUCRA = 48.7%). AZA combined with steroids might be an alternative immunosuppressive therapy. Tacrolimus might decrease the proteinuria level (RR = 3.1, 95% CI = 1.2-9.4, SUCRA = 66.5%) but cannot improve renal function, and the side effects of tacrolimus should not be neglected. MMF and CYC showed no superiority in the treatment of IgAN. In summary, steroids might be recommended as the first-line immunosuppressive therapy for IgAN.


Assuntos
Azatioprina/uso terapêutico , Glomerulonefrite por IGA/tratamento farmacológico , Imunossupressores/uso terapêutico , Ácido Micofenólico/uso terapêutico , Tacrolimo/uso terapêutico , Adulto , Azatioprina/administração & dosagem , Azatioprina/efeitos adversos , Ensaios Clínicos como Assunto , Combinação de Medicamentos , Feminino , Glucocorticoides/administração & dosagem , Glucocorticoides/efeitos adversos , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Resultado do Tratamento
18.
Medicine (Baltimore) ; 99(12): e19441, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32195940

RESUMO

We hypothesized that area under the concentration time curve (AUC(0-12)) is more accurate pharmacokinetic predictor vs trough level of mycophenolic acid (C0).Study was performed at the University Hospital of Limoges (France) and included 238 renal recipients aged 22 to 82 years. Risk of nephropathy was evaluated by analyzing data of protocol biopsies according to the Banff 97 classification.Assessment of immunosuppressants' exposures was based on the calculation of the mean of AUC(0-12). The AUC(0-12) was estimated using a Bayesian estimator and a 3-point limited sampling strategy. Cyclosporine and tacrolimus analyses were performed using liquid chromatography-mass spectrometry method. The measurement of total mycophenolic acid was performed using a validated high-performance liquid chromatography method with ultraviolet detection. IBM SPSS 20.0 was used for statistical analysis.The most accurate dosing of mycophenolate mofetil (MMF) was observed in patients receiving MMF with tacrolimus, 70.6% of patients' AUC(0-12) exposures were within the therapeutic range. The highest rates of low dosing were observed in patients receiving MMF with cyclosporine, 30.9% of patients had AUC(0-12) exposures below the therapeutic range. The assessment of AUC(0-12) revealed 38% of chronic nephropathy cases, while C0 enables to identify only 20% of chronic nephropathy cases.Probability test results showed that more likely AUC(0-12) and C0 will be maintained within the therapeutic width if patients receive MMF with tacrolimus vs MMF with cyclosporine: 0.6320 vs 0.6410 for AUC(0-12) determination and 0.8415 vs 0.4827 for C0 determination.Combination of MMF with tacrolimus is dosed more precisely vs dosing of MMF with cyclosporine. 72 (70.6%) patients AUC(0-12) and 79 (77.5%) patients C0 out of 102 patients were within the therapeutic range. The AUC(0-12) monitoring of mycophenolic acid in patients receiving MMF with tacrolimus or in patients receiving MMF with cyclosporine enabled to identify more overdosing and possible risky cases.Study results show that standard MMF dosing without monitoring and with mycophenolic acid level within the therapeutic width is possible and demonstrates less risky cases in patients receiving MMF with tacrolimus, while patients receiving MMF with cyclosporine should be intensively monitored to achieve the highest safety. However, AUC(0-12) monitoring is advised showing better compliance vs C0 monitoring.


Assuntos
Ciclosporina/uso terapêutico , Imunossupressores/farmacocinética , Imunossupressores/uso terapêutico , Transplante de Rim/métodos , Ácido Micofenólico/farmacocinética , Tacrolimo/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Ciclosporina/administração & dosagem , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Tacrolimo/administração & dosagem
19.
Transplant Proc ; 52(5): 1489-1492, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32217015

RESUMO

BACKGROUND AND AIM: Renal dysfunction is related to short- and long-term survival after liver transplantation. We present herein a retrospective analysis of our experience with liver transplantation in recipients with pretransplant renal dysfunction treated with induction therapy followed by delayed/reduced de novo once-daily tacrolimus. METHODS: Liver transplantations performed between April 2008 and August 2011 were included in this study. Pretransplant renal dysfunction was defined as estimated glomerular filtration rate <60 mL/min. Interleukin-2 receptor antagonists were used for induction therapy. Initial once-daily tacrolimus dose was 0.10 mg/kg/day or 0.07 mg/kg/day if combined with mycophenolate mofetil (MMF). Tacrolimus target trough levels were 4 to 6 ng/mL during the first post-transplant year and <4 ng/mL the rest of the follow-up. RESULTS: Nineteen patients comprised the study cohort with a median follow-up of 56.4 months (range, 11-78). Median day of tacrolimus introduction was 7 (range, 3-12). Once-daily tacrolimus was withdrawn in 6 patients (31.6%) due to evolution of renal dysfunction in all cases. At 5 years, 30% of the patients were under MMF monotherapy. Mean tacrolimus trough levels were maintained under 5 ng/mL. Mean estimated glomerular filtration rate at 5 years was 55.3 ± 12.7 mL/min. No patient needed hemodialysis or renal transplantation over the follow-up. Patient survival at 5 years was 78.9%. CONCLUSIONS: Induction therapy followed by delayed/reduced de novo once-daily tacrolimus and maintenance of low tacrolimus exposition during the follow-up is effective to maintain long-term renal function and to achieve favorable patient survival in liver transplant recipients with pretransplant renal dysfunction.


Assuntos
Imunossupressores/administração & dosagem , Nefropatias/tratamento farmacológico , Hepatopatias/cirurgia , Transplante de Fígado/mortalidade , Ácido Micofenólico/administração & dosagem , Tacrolimo/administração & dosagem , Idoso , Quimioterapia Combinada , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Quimioterapia de Indução , Rim/fisiopatologia , Nefropatias/complicações , Hepatopatias/complicações , Hepatopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Período Pré-Operatório , Estudos Retrospectivos , Resultado do Tratamento
20.
Neurology ; 94(15): e1645-e1656, 2020 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-32170036

RESUMO

OBJECTIVE: To compare the efficacy and the risk of severe infectious events of immunosuppressive agents used early as first-line therapy in patients with neuromyelitis optica spectrum disorder (NMOSD). METHODS: We retrospectively included patients with NMOSD and a seropositive status for aquaporin 4 or myelin oligodendrocyte glycoprotein antibodies beginning first-line immunosuppressants within 3 years after the disease onset. The main outcome was occurrence of relapse after the initiation of immunosuppressants; the secondary outcome was the annual relapse rate (AAR). RESULTS: A total of 136 patients were included: 62 (45.6%) were treated with rituximab (RTX), 42 (30.9%) with mycophenolate mofetil (MMF), and 23 (16.9%) with azathioprine (AZA). Compared with RTX-treated patients, the risk of relapse was higher among MMF-treated patients (hazard ratio [HR], 2.74 [1.17-6.40]; p = 0.020) after adjusting for age at disease onset, sex, antibody status, disease duration, ARR before treatment, corticosteroid intake, and relapse location. We did not observe any difference between RTX-treated and AZA-treated patients (HR, 2.13 [0.72-6.28]; p = 0.17). No interaction was found between the antibody status and immunosuppressive treatments. ARR was lower with RTX than with MMF (p = 0.039), but no difference was observed with AZA. We observed 9 serious infectious events with MMF, 6 with RTX, and none with AZA. CONCLUSIONS: The use of first-line RTX in NMOSD appears more effective than MMF in suppressing clinical activity, independent of the antibody status. CLASSIFICATION OF EVIDENCE: That study provides Class III evidence that for patients with NMOSD, first-line RTX is superior to MMF to reduce the risk of relapse.


Assuntos
Azatioprina/uso terapêutico , Imunossupressores/uso terapêutico , Ácido Micofenólico/uso terapêutico , Neuromielite Óptica/tratamento farmacológico , Adulto , Anticorpos/uso terapêutico , Aquaporina 4/efeitos dos fármacos , Aquaporina 4/imunologia , Azatioprina/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Neuromielite Óptica/imunologia , Recidiva , Rituximab/uso terapêutico
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