RESUMO
Eosinophilic fasciitis (EF) is an uncommon autoimmune connective tissue disorder characterized by edema, erythema, and subsequent induration of the extremities. It is commonly treated with corticosteroids but there is no treatment ladder for immunosuppressants or steroid-sparing agents. We report two EF cases treated effectively with mycophenolate mofetil (MMF) or mycophenolic acid (MPA) and present a literature review. We performed a MEDLINE search using the keywords 'eosinophilic fasciitis', 'Shulman syndrome', 'mycophenolic acid', or 'mofetil mycophenolate', and found 8 articles with 27 cases in which MMF or MPA was used. Twenty-nine cases were reviewed (2 reported herein and 27 from the literature search); all patients received a combination of systemic corticosteroids and MMF. MMF/MPA were given as a steroid-sparing agent in 27 (93.1%), in 1 (3.4%) as adjunctive therapy with other immunosuppressants, and in one, as monotherapy 1 (3.4%). Nineteen had a complete response, 6, a partial response, and 2 were unresponsive to diverse immunomodulators; in 2 cases, the outcome was not reported. MMF and MPA show promising therapeutic results and could be a treatment option to reduce corticosteroid related side effects.
Assuntos
Doenças Autoimunes , Fasciite , Doenças Autoimunes/tratamento farmacológico , Fasciite/induzido quimicamente , Fasciite/tratamento farmacológico , Glucocorticoides/uso terapêutico , Humanos , Imunossupressores/efeitos adversos , Ácido Micofenólico/efeitos adversos , Ácido Micofenólico/uso terapêuticoRESUMO
ABSTRACT Objective: Encapsulating peritoneal sclerosis (EPS) is a rare, but potentially fatal complication of peritoneal dialysis. Currently, treatment of peritoneal fibrosis is not fully possible yet. In this study, we aimed to demonstrate the effects of tacrolimus therapy on peritoneal fibrosis and inflammation when administered alone or with mycophenolate mofetil (MMF) in the EPS model induced in rats. Methods: Thirty six Wistar albino rats were separated into six equal groups. Group I was the control group. Group II-VI were administered intraperitoneal chlorhexidine (CH) for induced EPS model in rats. Group II, IV, V, VI were administered isotonic liquid, tacrolimus, tacrolimus and concurrently with CH, tacrolimus and MMF together, respectively. Group III was not administered any drug. All peritoneal samples were stained immunohistochemically with matrix metalloproteinase-2 (MMP-2) antibody. Thickness of peritoneal fibrosis, subserosal large collagen fibers, subserosal fibroblast proliferation and subserosal fibrotic matrix deposition were evaluated. Results: Comparing the experimentally induced EPS groups, the best histopathological results and the largest staining with MMP-2 were achieved in Group VI. Furthermore, in all treatment groups (IV, V, VI) more staining with MMP-2 was detected compared to non-treatment groups (I, II, III) but no statistically significant differences were found among all groups. A statistically significant remission was observed in all histopathological parameters, primarily peritoneal thickness in rats that were administered MMF with tacrolimus, compared to rats which were administered tacrolimus only. Conclusion: Concurrent use of tacrolimus and MMF in the treatment of EPS may be a promising approach.
RESUMEN Objetivos: La esclerosis peritoneal encapsulante (EPE) es una complicación rara, peropotencialmente fatal de la diálisis peritoneal. Actualmente, el tratamiento de la fibrosis peritoneal aún no es posible. En este estudio, apuntamos a demostrar los efectos de la terapia con tacrolimus en la fibrosis peritoneal y la inflamación cuando se administran solos o con micofenolato de mofetilo (MMF) en el modelo EPE inducido en ratas. Métodos: Treinta y seis ratas Wistar albinas se separaron en seis grupos iguales. El Grupo I era el grupo de control. En los grupos II-VI se administró clorhexidina intraperitoneal (CH) para el modelo EPE inducido en ratas. En los Grupos II, IV, V, VI se administró respectivamente líquido isotónico, tacrolimus, tacrolimus y CH y finalmente tacrolimus y MMF juntos. El grupo III no recibió ningún medicamento. Todas las muestras peritoneales se tiñeron inmunohistoquímicamente con el anticuerpo Matrix Metaloproteinasa-2 (MMP- 2). Se evaluó el grosor de la fibrosis peritoneal, se evaluaron las fibras de colágeno grandes subserosas, la proliferación de fibroblastos subserosa y la deposición de la matriz fibrótica subserosa. Resultados: Comparando los grupos de EPE inducidos experimentalmente, los mejores resultados histopatológicos y la tinción con MMP- 2 más extensa se lograron en el Grupo VI. Además, en todos los grupos de tratamiento (IV, V, VI) se detectó más tinción con MMP-2 en comparación con los grupos de no tratamiento (I, II, III), pero no se encontraron diferencias estadísticamente significativas entre todos los grupos. Se observó una remisión estadísticamente significativa en todos los parámetros histopatológicos, principalmente el espesor peritoneal en ratas que recibieron MMF con tacrolimus, en comparación con las ratas que recibieron solo tacrolimus. Conclusión: El uso concurrente de tacrolimus y MMF en el tratamiento de EPS puede ser una aplicación prometedora.
RESUMO
Coronavirus disease 2019 (COVID-19), an infection caused by severe acute respiratory syndrome coronavirus-type 2 (SARS-CoV-2), has emerged as a serious threat to public health. Liver transplant (LT) recipients may be at increased risk of acquisition of SARS-CoV-2 infection and higher morbidity and mortality due to constant contact with health-care services, the use of immunosuppressants and frequent comorbidities. In the first part of this review we discuss (1) the epidemiology and risk factors for SARS-CoV-2 infection in LT recipients; (2) the clinical and laboratory features of COVID-19 in this specific population, highlighting differences in presenting signs and symptoms with respect to general populations and (3) the natural history and prognostic factors in LT recipients hospitalized with COVID-19, with particular focus on the possible role of immunosuppression. Thereafter, we review the potential therapeutic options for COVID-19 treatment and prevention. Specifically, we give an overview of current practice in immunosuppressant regimen changes, showing the potential benefits of this strategy, and explore safety and efficacy issues of currently approved drugs in LT recipients. The last topic is dedicated to the potential benefits and pitfalls of vaccination.
RESUMO
AIMS: The final diagnosis of oral mucosal ulcerations in solid organ transplant recipients represents a challenge. We describe a unique case of oral ulceration related to mycophenolate mofetil (MMF) toxicity, 11 years after kidney transplantation, whose dose reduction was sufficient to resolve it. METHODS AND RESULTS: A 54-year-old female patient, who underwent kidney transplantation 11 years ago, presents multiple ulcers on the buccal mucosa bilaterally, soft palate and tongue dorsum, for 8 months, with moderate pain. The diagnosis of oral ulcerations associated with MMF therapy was assumed by excluding infection and malignancy diagnosis. After MMF dose reduction, the oral ulcers healed utterly. CONCLUSIONS: MMF toxicity manifested as oral ulcers. Reduction or discontinuation of MMF therapy should be considered in a patient with refractory oral ulcers and a negative workup for other causes.
Assuntos
Transplante de Rim , Úlceras Orais , Feminino , Rejeição de Enxerto , Humanos , Imunossupressores/efeitos adversos , Transplante de Rim/efeitos adversos , Pessoa de Meia-Idade , Ácido Micofenólico/efeitos adversos , Úlceras Orais/induzido quimicamente , Úlceras Orais/diagnósticoRESUMO
AIM: Describe characteristics and outcomes of three patients treated with pelvic radiation therapy after kidney transplant. BACKGROUND: The incidence of pelvic cancers in kidney transplant (KT) recipients is rising. Currently it is the leading cause of death. Moreover, treatment is challenging because anatomical variants, comorbidities, and associated treatments, which raises the concern of using radiotherapy (RT). RT has been discouraged due to the increased risk of urethral/ureteral stricture and KT dysfunction. MATERIALS AND METHODS: We reviewed the electronic health records and digital planning system of patients treated with pelvic RT between December 2013 and December 2018 to identify patients with previous KT. CASES DESCRIPTION: We describe three successful cases of KT patients in which modern techniques allowed full standard RT for pelvic malignances (2 prostate and 1 vaginal cancer) with or without elective pelvic nodal RT, without allograft toxicity at short and long follow-up (up to 60 months). CONCLUSION: When needed, RT modern techniques remain a valid option with excellent oncologic results and acceptable toxicity. Physicians should give special considerations to accomplish all OAR dose constraints in the patient's specific setting. Recent publications recommend KT mean dose <4â¯Gy, but graft proximity to CTV makes this unfeasible. We present 2 cases where dose constraint was not achieved, and to a short follow-up of 20 months renal toxicity has not been documented. We recommend the lowest possible mean dose to the KT, but never compromising the CTV coverage, since morbimortality from recurrent or progressive cancer disease outweighs the risk of graft injury.
RESUMO
Mycophenolate mofetil (MMF) is typically used in combination with prednisone and tacrolimus to avoid graft rejection in kidney transplant patients. The aim of this study was to develop and validate a population pharmacokinetic model of mycophenolic acid (MPA) in kidney transplant patients to investigate the influence of clinical and genetic covariates and to propose a dosage regimen based on the final model. Adult kidney transplant patients (>18 years old) receiving combination of MMF, prednisone and tacrolimus regimen were included. The population pharmacokinetic model was built using a two-compartment model and First Order Conditional Estimation method with Interaction (FOCEI though NONMEM v.7.4.). A total of 343 MPA concentrations at steady state from 77 kidney transplant patients were included in the analysis. MPA CL/F, V1/F, Q/F, V2/F, and Ka were 12.4 L/h, 45.6 L, 29.9 L/h, 658 L, and 1.67 h-1, respectively. It was found that CL/F increases with serum creatinine and uric acid levels and V1/F is modified by blood urea nitrogen and the UGT1A9 genotype. In the final model the interindividual variabilities associated to CL/F and V1/F were 56.5% and 105.8%, respectively. The residual variability was 41.8%. Evaluation by bootstrapping showed that the final model was stable. The predictive performance was evaluated by goodness-of-fit plots and visual predictive check. Dosage regimens for MMF were proposed based on the final model and would be appropriate for a prospective evaluation. In conclusion, it was built a population pharmacokinetic model for MPA in kidney transplant patients, which include clinical and genetic covariates.
Assuntos
Imunossupressores/farmacocinética , Transplante de Rim , Modelos Biológicos , Ácido Micofenólico/farmacocinética , Adolescente , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Interações Medicamentosas , Quimioterapia Combinada , Feminino , Glucuronosiltransferase/genética , Humanos , Imunossupressores/sangue , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/sangue , Ácido Micofenólico/uso terapêutico , Prednisona/uso terapêutico , Tacrolimo/uso terapêutico , UDP-Glucuronosiltransferase 1A , Ácido Úrico/sangue , Adulto JovemRESUMO
OBJECTIVES: Here, we aimed to compare the clinical effects of mycophenolate mofetil combined with either tacrolimus or with cyclophosphamide on lupus nephritis (LN) and to analyze their influence on the expression of cystatin C and on transforming growth factor-1 (TGF-β1). METHODS: A total of 234 patients were randomly divided into two groups: group A, for mycophenolate mofetil combined with tacrolimus (n=117) and group B, for mycophenolate mofetil combined with cyclophosphamide (n=117). The enzyme-linked immunosorbent assay was adopted to detect the expression levels of serum TGF-β1 and cystatin C before and after treatment. RESULTS: The total effectiveness rate in group A was much higher than that in group B. The times of effectiveness and effect validity in group A were much lower than those in group B. The expression levels of serum TGF-β1 and cystatin C decreased slightly after treatment in the two groups, and those of group A were much lower than those of group B. CONCLUSIONS: The combination of mycophenolate mofetil and tacrolimus showed better clinical efficacy on LN and was safer than that of mycophenolate mofetil and cyclophosphamide. Moreover, the drug combination of mycophenolate mofetil and tacrolimus greatly reduced the expression levels of serum TGF-β1 and cystatin C.
Assuntos
Humanos , Nefrite Lúpica/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Tacrolimo/uso terapêutico , Ciclofosfamida/uso terapêutico , Quimioterapia Combinada , Imunossupressores/uso terapêuticoRESUMO
BACKGROUND: Risk factors for cytomegalovirus (CMV) disease in renal transplant recipients have been evaluated in industrialized countries with relatively low CMV seroprevalence. OBJECTIVES: We aimed to determine which factors are related to this illness in a high CMV seroprevalence country. PATIENTS AND METHODS: A case-control study was performed with data from a 5-year follow-up of 260 kidney transplant recipients at our center. Odds ratios were calculated using the Mantel-Haenszel method. RESULTS: A total of 25 cases of CMV disease occurred during the study period. Recipient age greater than 55 years old (odds ratio: 4.95, 95% CI: 1.44-17.0) and use of thymoglobulin (odds ratio: 4.84; 95% CI: 1.10-21.39) were the only independent predictors for CMV disease. There was not any relationship between the previous serologic status of both donor and receptor and the occurrence of CMV disease. We did not observe any association between the immunosuppressive regimens and CMV disease, except for thymoglobulin. CONCLUSIONS: Only recipient age and thymoglobulin administration were related to CMV disease. Further studies are needed to determine if prophylactic treatment confers clinical benefit in this subset of patients.
RESUMO
RESUMEN Introducción: la esclerosis sistémica es una enfermedad autoinmune crónica, caracterizada por la tríada de vasculopatía de pequeños vasos, activación del sistema inmune y aumento de los depósitos de matriz extracelular tanto en la piel como en los órganos internos. En los últimos años, el compromiso pulmonar ha cobrado gran importancia, pasando a ser la primera causa de muerte, dada la disminución de la mortalidad por crisis renales con el advenimiento de los inhibidores de la enzima convertidora de angiotensina. La afección pulmonar puede ocurrir como hipertensión o enfermedad intersticial difusa; esta última es más común en pacientes con la variedad generalizada, en los primeros tres años de la enfermedad. Tiene mal pronóstico si no se inicia el tratamiento, cuya meta es detener el deterioro de la función pulmonar. Entre los tratamientos disponibles, la ciclofosfamida cuenta con la mejor evidencia, pero se están estudiando, con resultados preliminares satisfactorios, otros tratamientos como micofenolato mofetil, rituximab, trasplante autólogo de células hematopoyéticas y trasplante de pulmón. Objetivo: describir, de acuerdo con lo reportado en la literatura, la epidemiología, la fisiopatología, los métodos diagnósticos y el tratamiento de la enfermedad pulmonar intersticial en pacientes con esclerosis sistémica. Métodos: revisión estructurada, no sistemática de la literatura, enfocada en los aspectos de interés, mencionados y que incluyó 52 artículos.
SUMMARY Introduction: Systemic sclerosis is a chronic autoimmune disease, characterized by the triad of small vessel vasculopathy, immune system activation and increased deposits of extracellular matrix in the skin and internal organs. In the last few years, pulmonary involvement has gained relevance since the introduction of angiotensin enzyme converter inhibitors with the subsequent decline in scleroderma renal crisis mortality, transforming scleroderma lung disease in the leading cause of mortality. Pulmonary involvement can manifest as hypertension or interstitial lung disease, which usually occurs in patients with generalized scleroderma in the first three years of the disease. Its prognosis is poor without treatment which is aimed at stopping pulmonary function deterioration. Among treatment options, cyclophosphamide has the best evidence, and mycophenolate mofetil, rituximab, and stem cell and lung transplantation are currently under investigation with positive preliminary results. Objective: To describe, according to reports in the literature, epidemiology, pathophysiology, diagnostic methods, and treatment of interstitial lung disease in systemic sclerosis. Methods: Structured, non-systematic literature review, focused on the aforementioned aspects of interest. It included 52 articles.
RESUMO Introdução: a esclerose sistémica é uma doença autoimune crônica, caracterizada pela tríada de vasculopatia de pequenos vasos, ativação do sistema imune e aumento dos depósitos de matriz extracelular tanto na pele como nos órgãos internos. Nos últimos anos, o compromisso pulmonar há cobrado grande importância, passando a ser a primeira causa de morte, dada a diminuição da mortalidade por crises renais com o advento dos inibidores da enzima convertedora de angiotensina. A afecção pulmonar pode ocorrer como hipertensão ou doença intersticial difusa; esta última é mais comum em pacientes com a variedade generalizada, nos primeiros três anos da doença. Tem mal prognóstico se não se inicia o tratamento, cuja meta é deter o deterioro da função pulmonar. Entre os tratamentos disponíveis, a ciclofosfamida conta com a melhor evidência, mas se está estudando, com resultados preliminares satisfatórios, outros tratamentos como micofenolato mofetil, rituximab, transplante autólogo de células hematopoiéticas e transplante de pulmão. Objetivo: Descrever, de acordo com o reportado na literatura, a epidemiologia, a fisiopatologia, os métodos diagnósticos e o tratamento da doença pulmonar intersticial em pacientes com esclerose sistémica. Métodos: revisão estruturada, não sistemática da literatura, enfocada nos aspectos de interesse, mencionados e que incluiu 52 artigos.
Assuntos
Humanos , Escleroderma Sistêmico , Doenças Autoimunes , Doenças Pulmonares IntersticiaisRESUMO
Hypomyopathic dermatomyositis (HDM) is a rare form of dermatomyositis (DM). Interstitial lung disease (ILD) associated with clinically amyopathic DM (CADM-ILD) or hypomyopathic DM (HDM-ILD) is a rare condition with a more unfavorable prognosis than ILD associated with classic DM (CDM-ILD). There is no effective treatment for HDM-ILD. A 62-year-old woman with a 6-month history of chronic polyarthritis and myalgia presented skin lesions characteristic of DM (erythematous lesion on extensor surface of elbows, Gottron's papules, V-neck sign) with no clinical muscle impairment (global muscle strength: grade 5). Muscle enzymes (creatine kinase, lactic dehydrogenase, and aldolase) and electroneuromyography (ENMG) were normal. Computed tomography of the chest revealed ILD. Magnetic resonance imaging and muscle biopsy revealed subclinical muscle impairment. High doses of corticosteroids were used without success. As an alternative, 1500 mg/day of mycophenolate mofetil (MMF) was combined with low doses of prednisone, and the patient demonstrated a good clinical response after 3 months of this combination. Twenty-five months after initiating treatment, ILD remains in remission with the use of MMF and a low dose of prednisone. Therefore, MMF can be a good option for the treatment of HDM-ILD.
Assuntos
Anti-Inflamatórios/uso terapêutico , Dermatomiosite/tratamento farmacológico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Dermatomiosite/complicações , Quimioterapia Combinada , Feminino , Humanos , Doenças Pulmonares Intersticiais/complicações , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Resultado do TratamentoRESUMO
Abstract: The use of calcineurin inhibitors (CNI) after liver transplantation is associated with post-transplant nephrotoxicity. Conversion to mycophenolate mofetil (MMF) monotherapy improves renal function, but is related to graft rejection in some recipients. Our aim was to identify variables associated with rejection after conversion to MMF monotherapy. Conversion was attempted in 40 liver transplant recipients. Clinical variables were determined and peripheral mononuclear blood cells were immunophenotyped during a 12-month follow- up. Conversion was classified as successful (SC) if rejection did not occur during the follow-up. MMF conversion was successful with 28 patients (70%) and was associated with higher glomerular filtration rates at the end of study. It also correlated with increased time elapsed since transplantation, low baseline CNI levels (Tacrolimus ≤ 6.5 ng/mL or Cyclosporine ≤ 635 ng/mL) and lower frequency of tacrolimus use. The only clinical variable independently related to SC in multivariate analysis was low baseline CNI levels (p = 0.02, OR: 6.93, 95%, CI: 1.3-29.7). Mean baseline fluorescent intensity of FOXP3+ T cells was significantly higher among recipients with SC. In conclusion, this study suggests that baseline CNI levels can be used to identify recipients with higher probability of SC to MMF monotherapy. Clinicaltrials.gov identification: NCT01321112.
Assuntos
Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Transplante de Fígado , Tacrolimo/administração & dosagem , Ciclosporina/administração & dosagem , Inibidores de Calcineurina/administração & dosagem , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/efeitos dos fármacos , Imunossupressores/administração & dosagem , Ácido Micofenólico/administração & dosagem , Fatores de Tempo , Fatores de Transcrição/imunologia , Esquema de Medicação , Linfócitos T/imunologia , Distribuição de Qui-Quadrado , Razão de Chances , Análise Multivariada , Estudos Prospectivos , Fatores de Risco , Transplante de Fígado/efeitos adversos , Resultado do Tratamento , Tacrolimo/efeitos adversos , Monitoramento de Medicamentos/métodos , Ciclosporina/efeitos adversos , Quimioterapia Combinada , Inibidores de Calcineurina , Rejeição de Enxerto/imunologia , Imunossupressores/efeitos adversos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Ácido Micofenólico/efeitos adversosAssuntos
Transplante de Rim , Teratologia , Feminino , Humanos , Imunossupressores , Ácido Micofenólico , Gravidez , Resultado da Gravidez , Sistema de RegistrosRESUMO
ABSTRACT Purpose: To evaluate the efficacy and tolerance of mycophenolate mofetil (MMF) for the treatment of noninfectious uveitis using the methods advocated by the Standardization of Uveitis Nomenclature (SUN) Working Group and to compare this with other studies of immunosuppression in ocular inflammation. Methods: Retrospective case series. Patients with noninfectious uveitis, followed at a tertiary Uveitis Service in São Paulo, Brazil, from 2007 to 2014 and receiving oral MMF for a minimum of 6 months, were retrospectively reviewed. After reaching an optimal dose of MMF, patients were evaluated after 6 (T6), 12 (T12), and 24 months (T24). The optimal dose varied for each patient (medium 2.2 g/day, range 1.0-3.0 g/day). The main outcome measures were: 1) success on achieving complete control of inflammation in both eyes and/or oral prednisone dosage reduction to ≤10 mg per day, and 2) the length of time required to reduce oral prednisone to ≤10 mg/day, partial control of ocular inflammation, and side effects. Results: In a cohort of 16 patients with refractory noninfectious uveitis, 67% reached the ideal prednisone dose after 1 year of MMF treatment and 83% after 2 years of MMF treatment. Complete or partial inflammation control was achieved in 43.7% at T12. Two patients (14%) had disease remission after 4.7 years of MMF treatment. Adverse effects were gastrointestinal disturbances, infection, insomnia, and liver function abnormalities at a rate of 0.03 patient-year each. Conclusions: This small retrospective case series is consistent with the literature concerning the high efficacy and moderate tolerability of MMF in noninfectious uveitis. Observation of patients should be continued for at least 1 year to clearly determine MMF efficacy.
RESUMO Objetivo: Avaliar a eficácia e tolerância do micofenolato de mofetila (MMF) para o tratamento das uveítes não infecciosas refratárias, utilizando os métodos de análises definidos pelo "Standardization of Uveitis Nomenclature Working Group." Método: Estudo retrospectivo de série de casos. Foram incluídos pacientes com uveíte não infecciosa, em tratamento oral com MMF por um período mínimo de seis meses, acompanhados no Serviço de Uveítes, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brasil, no período de 2007 a 2014. Todos os pacientes faziam uso de pelo menos um imunossupressor e apresentavam doença ocular ativa. Os pacientes foram avaliados aos seis meses (T6), 12 meses (T12) e 24 meses (T24) após atingir a dose ótima do MMF. A média da dose ótima foi 2,2g/dia (intervalo 1,0-3,0g/dia). Os principais desfechos analisados foram: 1) Sucesso no controle total da inflamação em ambos os olhos e/ou redução da dose de prednisona oral para ≤10 mg/dia; 2) Intervalo até a redução da prednisona oral para ≤10 mg/dia, controle parcial de inflamação ocular e efeitos adversos. Resultados: Na presente coorte com 16 pacientes com uveíte não infecciosa refratária, observou-se 67% e 83% de probabilidade de alcançar a dose ideal de prednisona em T12 e T24, respectivamente. Controle total ou parcial da inflamação foi observado em 43,7% dos pacientes em T12. Dois pacientes (14%) tiveram remissão da doença após 4,7 anos do início de MMF. Os efeitos adversos foram distúrbios gastrintestinais, infecção, insônia e anormalidade da função hepática com 0,03 eventos paciente-ano (PPY) respectivamente. Conclusões: Esta pequena série retrospectiva de casos ratifica os achados na literatura sobre a alta eficácia e tolerância moderada de MMF em uveítes não infecciosas. Uma importante observação é que, para melhor avaliar a eficácia do MMF, deve se esperar o intervalo mínimo de um ano.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Uveíte/tratamento farmacológico , Imunossupressores/uso terapêutico , Ácido Micofenólico/uso terapêutico , Recidiva , Acuidade Visual , Administração Oral , Estudos Retrospectivos , Resultado do Tratamento , Imunossupressores/administração & dosagem , Ácido Micofenólico/administração & dosagemRESUMO
Optimal treatment for pure membranous lupus nephritis (MLN) remains unknown. The aim of this study was to evaluate the response to immunosuppressive treatment of Hispanics with pure MLN. This was a retrospective cohort analysis from a tertiary care center. Pure MLN patients were segregated into three groups according to the received induction treatment. All patients received adjunctive steroids. Outcomes included complete remission (CR), partial remission (PR), flare incidence, adverse events, and renal and patient survival. All outcomes were analyzed by Cox regression analysis. A total of 60 patients diagnosed with pure MLN between 2004 and 2014 were segregated into mycophenolate mofetil (MMF) (n = 18), intravenous cyclophosphamide (IVC) (n = 16), or azathioprine (AZA) (n = 26) groups. Complete remission rates at 6, 12, and 24 months were 33.3, 52.9, and 76.4 %, respectively, for MMF; 26.9, 42.3, and 54.6 %, respectively, for AZA; and 6.2, 14.8, and 26.9 %, respectively, for IVC. Based on Cox-adjusted analysis, treatment with MMF was associated with higher CR rates (hazard ratio (HR) 4.43, 1.19-16.4, p = 0.026) compared to IVC. There were no differences in CR rates between MMF and AZA groups. Patients treated with adjunctive antimalarial drugs were more likely to achieve CR (HR 2.46, 1.08-5.64, p = 0.032) and had a non-significant trend to lower incidence of thrombotic events (odds ratio (OR) 0.10, 0.010-1.14, p = 0.064). There were no differences in adverse events, renal flares, and renal or patient survival between groups. MMF might be superior to IVC as induction treatment for pure MLN in Hispanics, while AZA might remain as a valid alternative for treatment. Adjunctive treatment with an antimalarial drug may enhance renal response to therapy.
Assuntos
Azatioprina/uso terapêutico , Ciclofosfamida/uso terapêutico , Glomerulonefrite Membranosa/tratamento farmacológico , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Adolescente , Adulto , Quimioterapia Combinada , Feminino , Hispânico ou Latino , Humanos , Masculino , Prednisona/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Los efectos secundarios asociados al empleo de fármacos inmunosupresores son a menudo difícil de establecer, por la presencia de una enfermedad subyacente y al uso simultáneo de otros medicamentos, las reacciones adversas asociadas a la administración de micofenolato de mofetilo consiste principalmente en diarrea, leucopenia, vómitos, además de infección por citomegalovirus. Paciente de sexo femenino de 44 años, presenta un cuadro de 03 meses, presenta náuseas vómitos, diarrea y dolor abdominal tras la toma del micofenolato de mofetilo que se limita tras la no toma del medicamento. Una buena anamnesis y examen físico así como una biopsia duodenal dan una orientación clara para el diagnóstico
The side effects associated with the use of immunosuppressive drugs are often difficult to establish, by the presence of underlying disease and the concurrent use of other drugs, adverse reactions associated with the administration of mycophenolate mofetil consists mainly of diarrhea, leucopenia, vomiting, besides cytomegalovirus infection. Female, 44 years old, presents symptomatology of 03 months, vomiting nausea, diarrhea and abdominal pain after taking the mycophenolate mofetil, which is limited after not taking the drug. A good history and physical examination and a duodenal biopsy give a clear guidance for diagnosis
RESUMO
OBJECTIVE: Chronic rejection remains a major cause of graft failure with indication for re-transplantation. The incidence of chronic rejection remains high in the pediatric population. Although several risk factors have been implicated in adults, the prognostic factors for the evolution and reversibility of chronic rejection in pediatric liver transplantation are not known. Hence, the current study aimed to determine the factors involved in the progression or reversibility of pediatric chronic rejection by evaluating a series of chronic rejection cases following liver transplantation. METHODS: Chronic rejection cases were identified by performing liver biopsies on patients based on clinical suspicion. Treatment included maintaining high levels of tacrolimus and the introduction of mofetil mycophenolate. The children were divided into 2 groups: those with favorable outcomes and those with adverse outcomes. Multivariate analysis was performed to identify potential risk factors in these groups. RESULTS: Among 537 children subjected to liver transplantation, chronic rejection occurred in 29 patients (5.4%). In 10 patients (10/29, 34.5%), remission of chronic rejection was achieved with immunosuppression (favorable outcomes group). In the remaining 19 patients (19/29, 65.5%), rejection could not be controlled (adverse outcomes group) and resulted in re-transplantation (7 patients, 24.1%) or death (12 patients, 41.4%). Statistical analysis showed that the presence of ductopenia was associated with worse outcomes (risk ratio=2.08, p=0.01). CONCLUSION: The presence of ductopenia is associated with poor prognosis in pediatric patients with chronic graft rejection.
Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Adolescente , Rejeição de Enxerto/tratamento farmacológico , Imunossupressores/uso terapêutico , Tacrolimo/uso terapêutico , Biópsia , Doença Crônica , Ciclosporina/uso terapêutico , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto/efeitos dos fármacos , Nefropatias/cirurgia , Transplante de Fígado/efeitos adversos , Análise Multivariada , Ácido Micofenólico/uso terapêutico , Prognóstico , Indução de Remissão , Taxa de Sobrevida , Tacrolimo/sangueRESUMO
OBJECTIVE: To evaluate response rates in an adult lupus nephritis (LN) cohort in Mexico City, Mexico. METHODS: We analyzed 165 patients with biopsy-proven LN histological International Society of Nephrology/Renal Pathology Society classes III, IV, or V, distributed by treatment drug in 3 groups: mycophenolate mofetil (MMF; dosage > 2 g/day per 6 mos, n = 63), intravenous cyclophosphamide (IVC; 0.7 g/m(2) body surface area monthly per 6 pulses, n = 66), or azathioprine (AZA; dosage > 1.5 mg/kg/day per 6 mos, n = 36). Median followup was 31 ± 18 months. The primary endpoint was the proportion of patients achieving complete renal response (CR). Secondary endpoints included the proportion of patients achieving renal response (complete or partial), renal flare-free survival, doubling of serum creatinine, and progression to endstage renal disease (ESRD). RESULTS: MMF induction was superior to IVC (HR 2.00, 95% CI 1.23-3.25, p = 0.005) and AZA (HR 2.12, 95% CI 1.23-3.66, p = 0.007) in the primary endpoint. Censored CR rates at 6, 12, 24, and 36 months were 32.6%, 56.1%, 76.6%, and 94.1% for MMF; 24.2%, 34.4%, 57.9%, and 62.1% for IVC; and 8.4%, 39.8%, 49.7%, and 49.7% for AZA. MMF was also superior in renal response to treatment and renal flare-free survival outcomes. There were no differences between groups in doubling of serum creatinine or progression to ESRD. The induction treatment with MMF (HR 2.04, 95% CI 1.25-3.33, p = 0.005) and absence of vascular lesions on renal biopsy (HR 2.05, 95% CI 1.25-3.37, p = 0.004) were associated with CR, whereas proteinuria at the time of presentation was negatively associated with CR (HR 0.91, 95% CI 0.84-0.98, p = 0.013). CONCLUSION: MMF induction therapy is superior to IVC and AZA in patients with LN of Mexican-mestizo race.
Assuntos
Azatioprina/uso terapêutico , Ciclofosfamida/uso terapêutico , Imunossupressores/uso terapêutico , Nefrite Lúpica/tratamento farmacológico , Nefrite Lúpica/patologia , Ácido Micofenólico/análogos & derivados , Administração Oral , Corticosteroides/uso terapêutico , Adulto , Análise de Variância , Biópsia por Agulha , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Seguimentos , Hospitais de Ensino , Humanos , Imuno-Histoquímica , Imunossupressores/efeitos adversos , Infusões Intravenosas , Estimativa de Kaplan-Meier , Testes de Função Renal , Nefrite Lúpica/mortalidade , Masculino , México , Análise Multivariada , Ácido Micofenólico/uso terapêutico , Modelos de Riscos Proporcionais , Indução de Remissão , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
Diarrhea is a frequent and potentially severe complication of kidney transplantation. We describe here, in a cross-sectional study, the epidemiological and microbiological characteristics of acute and persistent diarrhea in 52 inpatients with kidney and kidney-pancreas transplant in a hospital in Buenos Aires, 42 (80.8%) of whom had received a kidney and 10 (19.2%) a kidney-pancreas transplant. Diarrhea was the reason of admission of 34 cases (65.4%). The etiology could be studied in 50 patients: 25 (50%) had no etiological diagnosis of diarrhea and 18 (36%) had a specific infectious etiology: 3 (6%) cytomegalovirus disease, 6 (12%) diarrhea attributed to cytomegalovirus, 5 (10%) to rotavirus and 4 (8%) to Clostridium difficile. In 7 (14%) diarrhea was attributed to drugs (mycophenolate mofetil and sirolimus). Patients with infectious diarrhea had recently received high doses of immunosuppressive therapy more frequently than the rest (p = 0.048). Those with diarrhea attributed to drugs were more frequently on mycophenolate mofetil than the rest (p = 0.039). Empirical modification of the immunosuppressive treatment was done in 16 (30.8%) and empirical antibiotic therapy was given to 47 patients (90.4%). Median length of hospital stay was 6 days. Seven patients (14.6%) persisted with diarrhea at the fifth day of admission. At hospital discharge all cases had complete resolution of symptoms and one third persisted with kidney failure. Information provided in this study can be useful as a starting point for improving preventive, diagnostic and therapeutic measures in these patients.
Assuntos
Infecções por Clostridium/complicações , Infecções por Citomegalovirus/complicações , Diarreia/etiologia , Transplante de Rim/efeitos adversos , Transplante de Pâncreas/efeitos adversos , Infecções por Rotavirus/complicações , Adulto , Clostridioides difficile/isolamento & purificação , Estudos Transversais , Feminino , Humanos , Imunossupressores/efeitos adversos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-IdadeRESUMO
La diarrea es una complicación frecuente y potencialmente grave del trasplante renal. Se describen aquí, en un estudio de corte transversal, las características epidemiológicas y microbiológicas de la diarrea aguda y persistente en pacientes internados con trasplante renal o reno-páncreas. Se incluyeron 52 pacientes internados en un hospital de la Ciudad de Buenos Aires, 42 (80.8%) habían recibido un trasplante renal y 10 (19.2%) reno-páncreas. La diarrea fue el motivo de ingreso en 34 casos (65.4%). La etiología de la diarrea pudo estudiarse en 50 pacientes: en 25 (50%) no se arribó a un diagnóstico etiológico y en 18 (36%) se constató diarrea con causa microbiológica específica: 3 (6%) enfermedad por citomegalovirus, 6 (12%) diarrea atribuida a citomegalovirus, 5 (10%) a rotavirus y 4 (8%) a Clostridium difficile. En 7 (14%) la diarrea fue atribuida a fármacos (mofetil micofenolato y sirolimus). Aquellos con diarrea con causa microbiológica habían recibido recientemente inmunosupresores a altas dosis con mayor frecuencia que el resto (p = 0.048). Los pacientes con diarrea atribuida a fármacos recibían más frecuentemente mofetil micofenolato (p = 0.039). En 16 (30.8%) se realizaron modificaciones de los inmunosupresores como medida terapéutica, y a 47 (90.4%) se les indicó antibioticoterapia empírica. La mediana de duración de internación fue de 6 días y 7 pacientes (14.6%) persistieron con diarrea al quinto día. Todos tuvieron resolución de la diarrea al alta y un tercio persistió con insuficiencia renal. La información de este estudio puede servir para mejorar las medidas preventivas, diagnósticas y terapéuticas en estos pacientes.
Diarrhea is a frequent and potentially severe complication of kidney transplantation. We describe here, in a cross-sectional study, the epidemiological and microbiological characteristics of acute and persistent diarrhea in 52 inpatients with kidney and kidney-pancreas transplant in a hospital in Buenos Aires, 42 (80.8%) of whom had received a kidney and 10 (19.2%) a kidney-pancreas transplant. Diarrhea was the reason of admission of 34 cases (65.4%). The etiology could be studied in 50 patients: 25 (50%) had no etiological diagnosis of diarrhea and 18 (36%) had a specific infectious etiology: 3 (6%) cytomegalovirus disease, 6 (12%) diarrhea attributed to cytomegalovirus, 5 (10%) to rotavirus and 4 (8%) to Clostridium difficile. In 7 (14%) diarrhea was attributed to drugs (mycophenolate mofetil and sirolimus). Patients with infectious diarrhea had recently received high doses of immunosuppressive therapy more frequently than the rest (p = 0.048). Those with diarrhea attributed to drugs were more frequently on mycophenolate mofetil than the rest (p = 0.039). Empirical modification of the immunosuppressive treatment was done in 16 (30.8%) and empirical antibiotic therapy was given to 47 patients (90.4%). Median length of hospital stay was 6 days. Seven patients (14.6%) persisted with diarrhea at the fifth day of admission. At hospital discharge all cases had complete resolution of symptoms and one third persisted with kidney failure. Information provided in this study can be useful as a starting point for improving preventive, diagnostic and therapeutic measures in these patients.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Infecções por Clostridium/complicações , Infecções por Citomegalovirus/complicações , Diarreia/etiologia , Transplante de Rim/efeitos adversos , Transplante de Pâncreas/efeitos adversos , Infecções por Rotavirus/complicações , Estudos Transversais , Clostridioides difficile/isolamento & purificação , Imunossupressores/efeitos adversos , Tempo de Internação/estatística & dados numéricosRESUMO
La diarrea es una complicación frecuente y potencialmente grave del trasplante renal. Se describen aquí, en un estudio de corte transversal, las características epidemiológicas y microbiológicas de la diarrea aguda y persistente en pacientes internados con trasplante renal o reno-páncreas. Se incluyeron 52 pacientes internados en un hospital de la Ciudad de Buenos Aires, 42 (80.8%) habían recibido un trasplante renal y 10 (19.2%) reno-páncreas. La diarrea fue el motivo de ingreso en 34 casos (65.4%). La etiología de la diarrea pudo estudiarse en 50 pacientes: en 25 (50%) no se arribó a un diagnóstico etiológico y en 18 (36%) se constató diarrea con causa microbiológica específica: 3 (6%) enfermedad por citomegalovirus, 6 (12%) diarrea atribuida a citomegalovirus, 5 (10%) a rotavirus y 4 (8%) a Clostridium difficile. En 7 (14%) la diarrea fue atribuida a fármacos (mofetil micofenolato y sirolimus). Aquellos con diarrea con causa microbiológica habían recibido recientemente inmunosupresores a altas dosis con mayor frecuencia que el resto (p = 0.048). Los pacientes con diarrea atribuida a fármacos recibían más frecuentemente mofetil micofenolato (p = 0.039). En 16 (30.8%) se realizaron modificaciones de los inmunosupresores como medida terapéutica, y a 47 (90.4%) se les indicó antibioticoterapia empírica. La mediana de duración de internación fue de 6 días y 7 pacientes (14.6%) persistieron con diarrea al quinto día. Todos tuvieron resolución de la diarrea al alta y un tercio persistió con insuficiencia renal. La información de este estudio puede servir para mejorar las medidas preventivas, diagnósticas y terapéuticas en estos pacientes.(AU)
Diarrhea is a frequent and potentially severe complication of kidney transplantation. We describe here, in a cross-sectional study, the epidemiological and microbiological characteristics of acute and persistent diarrhea in 52 inpatients with kidney and kidney-pancreas transplant in a hospital in Buenos Aires, 42 (80.8%) of whom had received a kidney and 10 (19.2%) a kidney-pancreas transplant. Diarrhea was the reason of admission of 34 cases (65.4%). The etiology could be studied in 50 patients: 25 (50%) had no etiological diagnosis of diarrhea and 18 (36%) had a specific infectious etiology: 3 (6%) cytomegalovirus disease, 6 (12%) diarrhea attributed to cytomegalovirus, 5 (10%) to rotavirus and 4 (8%) to Clostridium difficile. In 7 (14%) diarrhea was attributed to drugs (mycophenolate mofetil and sirolimus). Patients with infectious diarrhea had recently received high doses of immunosuppressive therapy more frequently than the rest (p = 0.048). Those with diarrhea attributed to drugs were more frequently on mycophenolate mofetil than the rest (p = 0.039). Empirical modification of the immunosuppressive treatment was done in 16 (30.8%) and empirical antibiotic therapy was given to 47 patients (90.4%). Median length of hospital stay was 6 days. Seven patients (14.6%) persisted with diarrhea at the fifth day of admission. At hospital discharge all cases had complete resolution of symptoms and one third persisted with kidney failure. Information provided in this study can be useful as a starting point for improving preventive, diagnostic and therapeutic measures in these patients.(AU)