Anemia hemolítica autoinmune en Chile: un análisis retrospectivo de 43 pacientes / Autoimmune hemolytic anemia: review of 43 cases

Background: Autoimmune hemolytic anemia (AIHA) is an uncommon disease. In its presentation, it can be severe and even lethal. There is only one clinical report concerning this pathology in Chile. Objective: To describe the clinical characteristics and evolution of adult AIHA inpatients. Materials and Methods: Retrospective review of clinical records of adult AIHA inpatients between January 2010 and June 2018 was done. Demographic, clinical, laboratory and therapeutic information was analyzed. A descriptive, analytical and survival analysis was performed. Results: Forty-three adult patients diagnosed with AHIA were hospitalized in a period of 8 years. Median age was 63 years (range 22-86 years), mostly women (72%). Warm antibodies were detected in 36 cases (84%) and cold antibodies in seven. Seventy two percent of the patients had an underlying cause, and 58% were secondary to lymphoproliferative neoplasms. All patients except two, received steroids as initial treatment, with response in 37 (90%) of them. Three refractory patients received rituximab, with response in all of them, and relapse in one. Median follow-up was 38 months (range 2-98 months). Five year overall survival was 72%. Conclusion: AHIA in adults inpatients is a heterogeneous disease, mainly due to warm antibodies, and to secondary etiology.

Histological remission of autoimmune hepatitis after the addition of allopurinol and azathioprine dose reduction

The standard therapy for some autoimmune diseases consists of a combination of corticosteroids and thiopurines. In non-responders to thiopurine drugs, the measurement of the metabolites of azathioprine, 6-thioguanine, and 6-methylmercaptopurine, can be a useful tool. The measurement has been used during the treatment of inflammatory bowel diseases and, less commonly, in autoimmune hepatitis. Many patients preferentially metabolize thiopurines to 6-methylmercaptopurine (6-MMP), which is potentially hepatotoxic, instead of 6-thioguanine, the active immunosuppressive metabolite. The addition of allopurinol shifts the metabolism of thiopurine towards 6-thioguanine, improving the immunosuppressive effect. We present the case of a 51-year-old female with autoimmune hepatitis who had a biochemical response after azathioprine and prednisone treatment without histological remission, and who preferentially shunted to 6-MMP. After the addition of allopurinol, the patient's 6-thioguanine levels increased, and she reached histological remission with a reduction of 67% of the original dose of azathioprine. The patient did not develop clinical manifestations as a consequence of her increased immunosuppressive state. We also review the relevant literature related to this issue. In conclusion, the addition of allopurinol to thiopurine seems to be an option for those patients who do not reach histological remission and who have a skewed thiopurine metabolite profile.

Eficacia y seguridad de rituximab en combinación con azatioprina o Mofetil micofenolato en pacientes adultos con diagnóstico de pénfigo refractario y con contraindicación a uso de corticoides por eventos adversos serios / Efficacy and safety of rituximab for the treatment of patients younger than 18 years with autoimmune encephalitis refractory to first-line therapy (immunoglobulin, corticoid pulses and plasmapheresis)

INTRODUCCIÓN: Antecedentes: El Instituto de Evaluación de Tecnologías en Salud e Investigación (IETSI) ha recibido la solicitud de evaluar el uso del medicamento Rituximab (RTX) administrado en asociación a azatioprina o mofetil micofenolato (MMF) en pacientes con pénfigo seborreico refractario y con contraindicaciones para el uso de corticoides por eventos adversos serios, indicación actualmente no contemplada en el petitorio de medicamentos. Aspectos Generales: El pénfigo es un grupo de enfermedades ampulosas autoinmunes raras caracterizado por formación de ampollas y erosiones extensas en la piel y las mucosas. El pénfigo aparece comúnmente en la edad adulta, su distribución es igual entre hombres y mujeres, y ocurre en todas las razas aunque se le ha encontrado asociado a algunos alelos del HLA clase II (Tron 2005), los cuales son moléculas heredadas relacionadas con la respuesta inmune. Fisiopatológicamente, las ampollas se producen debido a la presencia de auto-anticuerpos IgG contra la desmogleina 1 y 3 de los queratinocitos, las cuales son proteínas de adhesión localizadas en la parte superior e inferior de la epidermis respectivamente. Tecnología Sanitaria de Interés: Rituximab: RTX es un anticuerpo citolítico anti CD20. RTX se une al receptor del CD20 induciendo la disminución de células B in vitro. La molécula CD20 se expresa específicamente en la superficie de los linfocitos B durante su diferenciación desde células pre-B a células B maduras. El dominio Fab de RTX se une al antígeno CD20 de los linfocitos B, y el dominio Fc favorece funciones inmunes para mediar la lisis de las células B. Los posibles mecanismos de la lisis celular incluyen la citotoxicidad mediada por el sistema del complemento y mediada por anticuerpos (FDA). METODOLOGÍA: Estrategia de Búsqueda: Se realizó una búsqueda sistemática de la evidencia científica con respecto a la eficacia y seguridad de RTX en terapia combinada con azatioprina o MMFen pacientes con diagnóstico de pénfigo eritematoso refractario o con contraindicaciones para el uso de corticoides en las bases de datos MEDLINE, EMBASE y Translating research into practice (TRIPDATABASE), así como dentro de la información generada por grupos que realizan revisiones sistemáticas, evaluación de tecnologías sanitarias y guías de práctica clínica, tales como The Cochrane Library, The National Institute for Health and Care Excellence (NICE), The National Guideline for Clearinghouse (NGC) and The Canadian Agency for Drugs and Technologies in Health (CADTH). Los desenlaces clínicos a evaluar fueron mortalidad, remisión sostenida (definida como control de la enfermedad por más de 6 meses), calidad de vida, reacciones adversas, y disminución de la dosis de medicamentos coadyuvantes. Se hizo una búsqueda adicional en www.clinicaltrials.qov, para poder identificar ensayos clínicos en curso o que no hayan sido publicados. RESULTADOS: Sinopsis de la Evidencia: Se realizó una búsqueda de la literatura con respecto a la eficacia y seguridad de RTX en terapia combinada con azatioprina o MMF en pacientes con diagnóstico de pénfigo foliáceo (incluyendo el eritematoso) refractario o con contraindicaciones para el uso de corticoides. No se encontró ensayos clínicos aleatorizados que evaluaran a RTX como tratamiento de pénfigo foliáceo con o sin comparación con azatioprina o MMF por lo que se ha incluido resultados de estudios observacionales. CONCLUSIONES: Hasta el momento, no se ha identificado evidencia directa para responder si el uso de RTX en terapia combinada con azatioprina o mofetil MMFes mas efectiva y segura que la terapia con azatioprina o mofetil MMFen pacientes con diagnóstico de pénfigo eritematoso refractario y con contraindicaciones para el uso de corticoides por eventos adversos serios. No se ha encontrado en la presente evaluación de tecnología sanitaria evidencia consistente que establezca cual es el beneficio neto atribuible al uso de RTX por sobre otros inmunosupresores en pacientes con pénfigo eritematoso refractario y con contraindicación de uso de CE por eventos adversos severos, considerando que a la fecha se disponen de otros inmunosupresores de tercera línea recomendados en las guías consensuadas del manejo de pénfigo. expuesto El Instituto de Evaluación de Tecnologías en Salud e Investigación-IETSI no aprueba el uso de RTX como una alternativa de tratamiento para pacientes con diagnóstico de pénfigo eritematoso refractario y con contraindicación a uso de CE por efectos adversos severos.

Weekly azathioprine pulse versus daily azathioprinein the treatment of Parthenium dermatitis: A non-inferiority randomized controlled study.

Background: Azathioprine in daily doses has been shown to be effective and safe in the treatment of Parthenium dermatitis. Weekly pulses of azathioprine (WAP) are also effective, but there are no reports comparing the effectiveness and safety of these two regimens in this condition. Aims: To study the effi cacy and safety of WAP and daily azathioprine in Parthenium dermatitis. Methods: Sixty patients with Parthenium dermatitis were randomly assigned to treatment with azathioprine 300 mg weekly pulse or azathioprine 100 mg daily for 6 months. Patients were evaluated every month to assess the response to treatment and side effects. Results: The study included 32 patients in the weekly azathioprine group and 28 in the daily azathioprine group, of whom 25 and 22 patients respectively completed the study. Twenty-three (92%) patients on WAP and 21 (96%) on daily azathioprine had a good or excellent response. The mean pretreatment clinical severity score decreased from 26.4 ± 14.5 to 4.7 ± 5.1 in the WAP group, and from 36.1 ± 18.1 to 5.7 ± 6.0 in the daily azathioprine group, which was statistically signifi cant and comparable (P = 0.366). Patients on WAP had a higher incidence of adverse effects (P = 0.02). Limitations: The study had a small sample size and the amount of clobetasol propionate used in each patient was not determined, though it may not have affected the study outcome due to its comparable use in both groups. Conclusions: Azathioprine 300 mg weekly pulse and 100 mg daily dose are equally effective and safe in the treatment of Parthenium dermatitis.

Determinación de la tiopurina metiltransferasa para ajustar la dosis de azatioprina o mercaptopurina: [revisión] / Monitoring thiopurine methyltransferase activity to adjust dosages of azathioprine or mercaptopurine: [review]

La monitorización de la actividad de la tiopurina metiltransferasa (TPMT) se emplea para identificar a los pacientes tratados con azatioprina (AZA) y mercaptopurina (MP) que presentan mayor riesgo de mielotoxicidad. La actividad de la TPMT en la población general sigue una distribución trimodal, en la que aproximadamente el 11% de los individuos son heterocigotos y el 0.3% homocigotos para el alelo de baja actividad. Existen dos estrategias para identificar los pacientes con deficiencia de TPMT: la medición del fenotipo y del genotipo, con una elevada concordancia entre ambas técnicas. Se demostró una notable correlación entre el fenotipo o el genotipo de baja actividad de la TPMT y el riesgo de mielotoxicidad. Los pacientes con un genotipo homocigoto de alta actividad (o con actividad normal de la TPMT) deberían recibir dosis de inmunosupresores que hayan demostrado ser claramente eficaces. En aquellos enfermos con genotipo o fenotipo homocigoto de baja actividad de la TPMT se debería contraindicar el empleo de AZA/MP o, en todo caso, sería obligado administrar dosis muy reducidas de estos fármacos. En resumen, la determinación de la actividad de la TPMT constituye una atractiva opción para individualizar la dosis de AZA o MP y prevenir el riesgo de efectos adversos, aunque está por demostrarse si esta estrategia debe aplicarse rutinariamente en todos los pacientes. En cualquier caso, el fenotipo o el genotipo asociado con el déficit de TPMP explica únicamente un porcentaje de casos de mielotoxicidad, por lo que los controles analíticos periódicos deben seguir realizándose en estos pacientes a pesar de que la función de esta enzima sea normal.

Recurrent Bilateral Branch Retinal Artery Occlusion with Hearing Loss and Encephalopathy: The First Case Report of Susac Syndrome in Korea

We report the first case of Susac syndrome in Koreans, in a 23-yr-old female patient who presented with sudden visual loss and associated neurological symptoms. Ophthalmic examination and fluorescein angiography showed multiple areas of branch retinal artery occlusion, which tended to recur in both eyes. Magnetic resonance imaging showed dot-like, diffusion-restricted lesions in the corpus callosum and left fornix, and audiometry showed low-frequency sensory hearing loss, compatible with Susac syndrome. She received immunosuppressive therapy with oral steroid and azathioprine. Three months later all the symptoms disappeared but obstructive vasculitis have been relapsing. This patient demonstrated the entire clinical triad of Susac syndrome, which tends to occur in young females. Although this disorder has rarely been reported in Asian populations, a high index of suspicion is warranted for early diagnosis and timely treatment.

Toxicidade da azatioprina na doença de Crohn: incidência, abordagem e evolução / Azathioprine toxicity in Crohn's disease: incidence, approach and course

OBJETIVO: A azatioprina (AZA) tem sido usada freqüentemente no tratamento da doença de Crohn (DC). O objetivo do presente estudo foi avaliar a freqüência, evolução e abordagem dos efeitos adversos da AZA no tratamento de pacientes com DC. MÉTODOS: Foram incluídos prospectivamente 106 pacientes portadores de DC em uso de AZA, de janeiro de 2002 a dezembro de 2006. Registraram-se dados clínicos e demográficos, com controle laboratorial mensal dos efeitos hematológicos e supervisão de reações adversas por meio de avaliação clínica. Realizou-se comparação entre os grupos com e sem efeitos adversos. RESULTADOS: Cinqüenta e seis (52,7 por cento) dos pacientes estudados apresentaram pelo menos um efeito adverso, requerendo redução transitória da dose da droga; 18 (17 por cento) necessitaram suspender definitivamente o uso de AZA, geralmente devido a reações de hipersensibilidade. Náuseas e vômitos, freqüentemente leves, ocorreram em 29 (27,4 por cento); a raça negra e aqueles com comorbidades apresentaram mais intolerância gástrica do que os brancos e aqueles sem outras doenças associadas (p=0,04). Leucopenia foi o efeito adverso mais freqüente, ocorrendo em 36 (34 por cento). O tempo de uso de AZA foi maior em pacientes com leucopenia do que nos não leucopênicos (p=0,001), enquanto a dose média de AZA foi menor naqueles com leucopenia comparados aos não leucopênicos (p=0,005). Não houve infecções graves, neoplasias ou óbitos durante o tratamento com AZA. CONCLUSÃO: A AZA mostrou ser uma droga relativamente segura no tratamento da DC, desde que seja mantida supervisão clínica e laboratorial periódica durante todo o tratamento.

OBJECTIVE: Azathioprine (AZA) is frequently used in Crohn's disease (CD) therapy. This paper aimed to evaluate the frequency, evolution and management of AZA side effects in CD patients. METHODS: One hundred and six CD patients under AZA therapy were evaluated prospectively from January 2002 to December 2006. Clinical and demographic data were recorded, together with a monthly laboratory control of hematological or other adverse reactions by means of clinical evaluation. Comparison was carried out between groups with and without side effects. RESULTS: At least one adverse reaction was found in 56 (52.7 percent) of the patients studied and required a transient drug reduction; 18 (17 percent) had to definitely stop use of AZA, often because of hypersensitivity reactions. Nausea, vomit, although slight, occurred in 29 (27.4 percent). The black race and those with co-morbidities had more gastric intolerance than Caucasians and those without other associated disease (p=0.04). Leucopoenia was the more frequent side effect observed, occurring in 36 (34 percent). The period of AZA use was longer for patients with leucopoenia than for those without (p=0.001), while the mean dose of AZA was lower for those with leucopoenia when compared to non-leucopoenics (p=0.005). No serious infections, malignancy or death was noticed as a consequence of AZA use. CONCLUSION: In this study use of AZA in therapy for Crohn's disease disclosed that the drug is satisfactorily safe as long as periodical clinical and laboratory supervision is carried out during treatment.

Monitoração terapêutica da azatioprina: uma revisão: [revisão] / Therapeutic drug monitoring of azathioprine: a review: [review]

Os nucleotídeos de tioguanina (6-TGN), metabólitos ativos da azatioprina (AZA) e da 6-mercaptopurina (6-MP), atuam como antagonistas das purinas, inibindo as sínteses de DNA, RNA e a protéica, e induzindo à citotoxicidade/imunossupressão. A enzima geneticamente determinada, tiopurina metiltransferase (TPMT), está envolvida no metabolismo desses agentes e, hipoteticamente, determina a resposta clínica às tiopurinas. A baixa atividade dessa enzima diminui a metilação das tiopurinas, resultando em potencial sobredose, enquanto altos níveis de TPMT levam à superprodução do metabólito tóxico 6-metilmercaptopurina (6-MMP) e à não-efetividade terapêutica da AZA e da 6-MP. Várias mutações no gene da TPMT têm sido identificadas e correlacionadas com fenótipos de baixa atividade. Neste artigo, também se discute a monitoração terapêutica desses fármacos por meio da medida dos níveis de 6-TGN intra-eritrocitários, os quais se correlacionam com imunossupressão e mielotoxicidade. Já a 6-MMP está diretamente relacionada com hepatotoxicidade. Esses ensaios estão associados ao uso de doses adequadas dessa droga, resultando num melhor controle da doença e menor uso de corticosteróides.

Thioguanine nucleotides (6-TGN), active metabolites of azathioprine (AZA) and 6-mercaptopurine (6-MP), act as purine antagonists, inhibiting DNA, RNA, and protein synthesis and inducing cytotoxicity and immunosuppression. The genetically determined thiopurine methyltransferase enzyme (TPMT) is involved in the metabolism of these agents and, theoretically, determines the clinical response to thiopurines. Low activity of this enzyme decreases the methylation of thiopurines, what results in potential overdosing, whereas high TPMT status leads to overproduction of toxic metabolite 6-methilmercaptopurine (6-MMP) and ineffectiveness of AZA and 6-MP. Several mutations in the TPMT gene have been identified and correlated with low activity phenotypes. In this study, we also discuss the therapeutic monitoring of these drugs by means of red blood cell 6-TGN levels, which correlate with immunosuppression and mielotoxicity. 6-MMP is directly connected with hepatotoxicity. These metabolites assays are associated with the use of appropriate doses of this drug, what results in a better control of the disease and a decreased use of corticosteroids.

Oclusão venosa central de retina na remissão de doença de Crohn: relato de caso / Retinal central vein occlusion in remission of Crohn's disease: case report

As doenças inflamatórias intestinais consistem na doença de Crohn e na retocolite ulcerativa. São caracterizadas pela inflamação crônica das alças intestinais. Os estudos e pesquisas sobre o processo inflamatório trouxeram avanços quanto ao tratamento destas doenças. As complicações sistêmicas das doenças inflamatórias intestinais envolvem muitos órgãos, incluindo os olhos. A verdadeira incidência de complicações oculares nas doenças inflamatórias intestinais é desconhecida, mas de acordo com a literatura varia de 3,5 por cento a 11,8 por cento. As complicações oftalmológicas normalmente têm origem inflamatória. Os autores descrevem um caso clínico de uma paciente portadora de doença de Crohn que desenvolveu oclusão venosa central da retina (OVCR) e papiloflebite, sem nenhuma outra doença retiniana vascular associada, durante a fase de remissão da doença. O objetivo deste relato de caso é reforçar a importância da realização do exame oftalmológico completo de rotina nas doenças inflamatórias intestinais.

Inflammatory bowel disease (IBD) includes Crohn's disease and ulcerative colitis. Both diseases are characterized by chronic inflammation of the intestines. The advances in understanding the inflammatory process improved the treatment of inflammatory bowel disease. The systemic complications of inflammatory bowel disease involve several organs included the eyes. The incidence of eye complications in IBD is unknown, but according to the literature the incidence vary between 3.5 percent and 11.8 percent. The ophthalmic complications are usually of inflammatory origin. We report a case of a patient with Crohn's disease that developed central retinal vein occlusion and papillophlebitis without any other retinal vascular disease during remission. The aim of this paper is to reinforce the importance of complete ophthalmic examination perform as a routine in patients with inflammatory bowel disease.

Hemossiderose pulmonar idiopática tratada com azatioprina: relato de caso em criança / Idiopathic pulmonary hemosiderosis treated with azathioprine in a child

A hemossiderose pulmonar idiopática (HPI), principal causa de hemossiderose pulmonar em crianças, cursa com sangramento alveolar intermitente e presença de hemossiderófagos no escarro ou no lavado gástrico. O tratamento é baseado nos corticoesteróides e citostáticos, em condições especiais. Descreve-se o caso de uma menina de sete anos com HPI, que conseguiu controle parcial da doença mediante altas doses de corticoesteróide. O tratamento, no entanto, necessitou ser suspenso gradualmente visto a paciente ter desenvolvido fácies cushingóide. Foi iniciada a associação da azatioprina ao corticóide até a substituição total por azatioprina isolada, cujo uso foi mantido por quatro anos, com ótimo resultado.

Idiopathic pulmonary hemosiderosis (IPH), the main cause of pulmonary hemosiderosis in children, is characterized by intermittent alveolar bleeding and hemosiderin-laden macrophages in sputum and in gastric lavage. The treatment is based on corticosteroids and cytotoxic drugs, under special conditions. We describe the case of a 7-year-old girl with IPH who achieved partial clinical remission with high doses of corticosteroids. However, the treatment had to be discontinued because the patient developed Cushing's syndrome. Treatment was started with an azathioprine-corticosteroid combination and then changed to azathioprine alone, which was maintained for four years, with excellent results.

An experimental model for the study of drug effects on cutaneous healing / Modelo experimental para o estudo de efeitos de drogas sobre a cicatrização cutânea

PURPOSE: Immunosuppressive agents are known to interfere with the healing of surgical wounds. The increasing use of these drugs warrants a better understanding of their effects on wound healing. The aim of this study was to develop an experimental model that would allow for a reliable and rapid assessment of drug effects on cutaneous wound healing. METHODS: Thirty syngeneic Lewis rats underwent surgical incision on their dorsal region, in the presence or absence of a three-week regimen of immunosuppressant drug therapy (i.e., cyclosporin, azathioprine, and prednisone). Surgical site tissue was collected at intervals over 21 days after surgery and analyzed for cell number and collagen fiber content. Both of these quantitative assessments were performed using digital image capture with the Image Pro Plus 4.5 software. RESULTS: Computerized histomorphometric analyses revealed an apparent inhibition of cellular responses and collagen fiber production in drug-treated animals compared to control animals. CONCLUSION: The experimental model was reproducible, easy to perform, and allowed for quantitative histological evaluations. It may be useful for the study of surgical healing in the presence of other drug classes.

OBJETIVO: Várias drogas podem interferir no processo de cicatrização de feridas cirúrgicas, incluindo-se aqui agentes imunossupressores. Devido ao crescimento do número de pessoas tratadas com estas drogas, um modelo experimental, baseado em um sistema computadorizado de avaliação histológica, para verificar os efeitos destas drogas sobre a cicatrização cirúrgica pode se mostrar útil e permitir, também, o estudo das ações de outras drogas sobre este processo. MÉTODOS: Trinta ratos Lewis isogênicos foram submetidos a incisões cirúrgicas na região dorsal e metade deles foi imunossuprimida utilizando-se ciclosporina, azatioprina e prednisona por 3 semanas. Em cinco intervalos de tempo pré-fixados, avaliações histológicas quantitativas de células e fibras colágenas dos sítios operatórios de animais tratados e controles foram realizadas, utilizando-se captura digital das imagens por meio do programa Image Pro Plus 4.5. RESULTADOS: A avaliação dos sítios cirúrgicos mostrou, nos animais sob uso de drogas imuossupressoras, aparente diminuição no número de células e na produção de fibras colágenas. CONCLUSÕES: O modelo experimental proposto mostrou-se viável por exigir recursos pouco sofisticados, pela fácil realização e por fornecer avaliações histológicas quantitativas. Este modelo poderá ser utilizado para o estudo da ação de outras classes de drogas sobre a cicatrização cirúrgica.

Parthenium dermatitis treated with azathioprine weekly pulse doses.

BACKGROUND: Parthenium dermatitis is a serious problem in India. Corticosteroids are the mainstay of treatment but the prolonged use of corticosteroids can cause serious side effects. Azathioprine used in daily doses has been shown to be effective. AIM: We have evaluated the effectiveness of azathioprine weekly pulse doses for the treatment of parthenium dermatitis. METHODS: Twelve patients, ten males and two females, aged between 39 and 65 years (mean +/- SD = 53.5 +/- 8.7) having air-borne contact dermatitis to Parthenium hysterophorus for 3-19 years (mean = 6.33) were included in the study. The diagnosis in each patient was confirmed by patch-testing. The severity of the disease was determined by clinical severity score (CSS) on the basis of erythema, itching, type of lesions, and areas of body involved. RESULTS: The pretreatment CSS in these patients varied from 29.7 to 55.5 (mean +/- SD: 40.40 +/- 7.95). After clinical and laboratory evaluation, the patients were treated with 300-mg azathioprine once-weekly doses for 6 months. Clinical and laboratory evaluations were repeated at weeks 1, 2, and then every 4 weeks until the end of therapy to evaluate the therapeutic response and side effects. The response was excellent (80-100% clearance of disease) in seven (58.33%) patients and good (60% clearance) in five (41.66%) patients. The post-treatment CSS decreased from the mean +/- SD of 40.4 +/- 7.95 to 10.9 +/- 8.43 (P = 0.002). There were no significant side effects of the therapy. CONCLUSIONS: In this preliminary open study, azathioprine in weekly pulse doses has been found to be effective without any serious adverse effects in the treatment of parthenium dermatitis. The cost of therapy with this regimen is reduced by 60%.

Impact of initial exposure to calcineurin inhibitors on kidney graft function of patients at high risk to develop delayed graft function

We conducted a retrospective analysis of the influence of full doses of calcineurin inhibitors [8-10 mg kg-1 day-1 cyclosporine (N = 80), or 0.2-0.3 mg kg-1 day-1 tacrolimus (N = 68)] administered from day 1 after transplantation on the transplant outcomes of a high-risk population. Induction therapy was used in 13 percent of the patients. Patients also received azathioprine (2 mg kg-1 day-1, N = 58) or mycophenolate mofetil (2 g/day, N = 90), and prednisone (0.5 mg kg-1 day-1, N = 148). Mean time on dialysis was 79 ± 41 months, 12 percent of the cases were re-transplants, and 21 percent had panel reactive antibodies >10 percent. In 43 percent of donors the cause of death was cerebrovascular disease and 27 percent showed creatinine above 1.5 mg/dL. The incidence of slow graft function (SGF) and delayed graft function (DGF) was 15 and 60 percent, respectively. Mean time to last dialysis and to nadir creatinine were 18 ± 15 and 34 ± 20 days, respectively. Mean creatinine at 1 year after transplantation was 1.48 ± 0.50 mg/dL (DGF 1.68 ± 0.65 vs SGF 1.67 ± 0.66 vs immediate graft function (IGF) 1.41 ± 0.40 mg/dL, P = 0.089). The incidence of biopsy-confirmed acute rejection was 22 percent (DGF 31 percent, SGF 10 percent, IGF 8 percent). One-year patient and graft survival was 92.6 and 78.4 percent, respectively. The incidence of cytomegalovirus disease, post-transplant diabetes mellitus and malignancies was 28, 8.1, and 0 percent, respectively. Compared to previous studies, the use of initial full doses of calcineurin inhibitors without antibody induction in patients with SGF or DGF had no negative impact on patient and graft survival.

Relationship of cyclosporin and sirolimus blood concentrations regarding the incidence and severity of hyperlipidemia after kidney transplantation

The influence of drug concentrations on the development of persistent posttransplant hyperlipidemia was investigated in 82 patients who received cyclosporin A (CsA) and prednisone plus sirolimus (SRL) (52) or azathioprine (AZA) (30) during the first year after transplantation. Blood levels of CsA and SRL, daily doses of AZA and prednisone, and cholesterol, triglyceride, and glucose concentrations were determined during each visit (pretransplant and 30, 60, 90, 120, 180, and 360 days posttransplant). Persistent hyperlipidemia was defined as one-year average steady-state cholesterol (CavCHOL) or triglyceride (CavTG) concentrations above 240 and 200 mg/dL, respectively. Mean cholesterol and triglyceride concentrations increased after transplantation (P < 0.01) and were higher in patients receiving SRL compared to AZA (P < 0.001). Patients receiving SRL showed a significantly higher number of cholesterol (>229 or >274 mg/dL) and triglyceride (>198 or >282 mg/dL) determinations in the upper interquartile ranges. CsA and SRL interquartile ranges correlated with cholesterol concentrations (P = 0.001) whereas only SRL interquartile ranges correlated with triglyceride concentrations (P < 0.0001). Only pretransplant cholesterol concentration >205 mg/dL was independently associated with development of persistent hypercholesterolemia (CavCHOL >240 mg/dL, relative risk (RR) = 20, CI 3.8-104.6, P = 0.0004) whereas pretransplant triglyceride concentration >150 mg/dL (RR = 7.2, CI 1.6-32.4, P = 0.01) or >211 mg/dL (RR = 19.8, CI 3.6-107.9, P = 0.0006) and use of SRL (RR = 3, CI 1.0-8.8, P = 0.0049) were independently associated with development of persistent hypertriglyceridemia (CavTG >200 mg/dL). Persistent hypercholesterolemia was more frequent among patients with higher pretransplant cholesterol concentrations and was dependent on both CsA and SRL concentrations. Persistent hypertriglyceridemia was more frequent among patients with higher pretransplant triglyceride concentrations and was dependent on SRL concentrations.

Autoimmune Hepatitis: Recent Update on Diagnosis and Treatment / 대한간학회지

Autoimmune hepatitis (AIH) is an unresolving, predominantly periportal hepatitis that is usually displays hypergammaglobulinemia, and tissue autoantibodies, and this malady is responsive to immunosuppressive therapy. Our understanding about this clinical entity has been greatly expanded since the first description by Waldenstrom 50 years ago. The codified diagnostic criteria of AIH prepared by International Autoimmune Hepatitis Group are still valid, but new attempts are being made to overcome the shortcomings of this scoring system. Immunosuppressive therapies using prednisone and azathioprine are currently the mainstay for the treatment of AIH, but there are still many practical questions to be solved.