[Eculizumab for the treatment of atypical hemolytic uremic syndrome: case report and revision of the literature]. / Uso do eculizumab na síndrome hemolítica urêmica atípica: relato de caso e revisão da literatura.

SHU atypical (aHUS), that is, not associated with Escherichia coli Shiga toxinproducing, is seen in 5 to 10% of cases of Hemolytic Uremic Syndrome (HUS), and can occur at any age and may be sporadic or familial. The prognosis in these cases is reserved, with high mortality and morbidity in the acute phase of the disease, and about 50% of cases can develop chronic kidney disease. The increased knowledge of the pathogenesis of aHUS (overactivation of the alternative pathway of complement), was accompanied by the appearance of a drug, eculizumab, which acts as an inhibitor of membrane attack complex. Our goal is to report a case of infant with aHUS with excellent clinical and laboratory response with the use of eculizumab. 14 month old infant, previously healthy, male, presented anemia and thrombocytopenia at 12 months of age. He was treated with corticosteroids and forwarded to our service for high blood pressure. However, the scans showed nephrotic proteinuria with renal involvement and hypoalbuminemia with direct Coombs negative. He developed anemia, thrombocytopenia, worsening of renal function and hypertension. Renal biopsy showed thrombotic microangiopathy (TMA). On the non-hemolytic anemia, thrombocytopenia and acute renal failure with histological substrate MAT, was diagnosed of aHUS. The patient received eculizumab excellent clinical and laboratory response. This case shows the importance of early diagnosis and treatment of the aHUS. Eculizumab is effective and keeps long-term remission, avoiding invasive measures such as plasmapheresis, which resolves only part of the picture.

Uso do eculizumab na síndrome hemolítica urêmica atípica: relato de caso e revisão da literatura / Eculizumab for the treatment of atypical hemolytic uremic syndrome: case report and revision of the literature

Síndrome Hemolítico Urêmica atípica (SHUa), isto é, não associada à Escherichia coli, produtora de Shiga toxina, é vista em 5% a 10% dos casos de Síndrome Hemolítico Urêmica (SHU), podendo ocorrer em qualquer idade e ser esporádica ou familiar. O prognóstico nestes casos é reservado, com alta mortalidade e morbidade na fase aguda da doença, e cerca de 50% dos casos podem evoluir para doença renal crônica terminal. O aumento do conhecimento da patôgenese da SHUa (hiperativação da via alternativa do complemento) foi acompanhado pelo surgimento de uma droga, eculizumab, a qual age como inibidor da via final do complemento. Nosso objetivo é relatar um caso de lactente com SHUa que apresentou excelente resposta clínica e laboratorial com o uso de eculizumab. Lactente, 14 meses de idade, sexo masculino, previamente hígido, apresentou quadro de anemia e plaquetopenia aos 12 meses de idade. Foi tratado com corticoterapia e encaminhado ao nosso serviço por hipertensão arterial. Entretanto, os exames demonstraram acometimento renal com proteinúria nefrótica e hipoalbuminemia, com Coombs direto negativo. Evoluiu com anemia, plaquetopenia, piora de função renal e hipertensão. Realizada biópsia renal que mostrou microangiopatia trombótica (MAT). Diante do quadro de anemia não hemolítica, plaquetopenia e insuficiência renal aguda com substrato histológico de MAT, foi feito diagnóstico de SHUa. O paciente recebeu eculizumab, com excelente resposta clínico-laboratorial. Este caso denota a importância de diagnóstico e tratamento precoces nesta entidade grave que é a SHUa. Eculizumab é eficaz e mantém remissão a longo prazo, evitando medidas invasivas como a plasmaferese, a qual resolve apenas parcialmente o quadro.

SHU atypical (aHUS), that is, not associated with Escherichia coli Shiga toxinproducing, is seen in 5 to 10% of cases of Hemolytic Uremic Syndrome (HUS), and can occur at any age and may be sporadic or familial. The prognosis in these cases is reserved, with high mortality and morbidity in the acute phase of the disease, and about 50% of cases can develop chronic kidney disease. The increased knowledge of the pathogenesis of aHUS (overactivation of the alternative pathway of complement), was accompanied by the appearance of a drug, eculizumab, which acts as an inhibitor of membrane attack complex. Our goal is to report a case of infant with aHUS with excellent clinical and laboratory response with the use of eculizumab. 14 month old infant, previously healthy, male, presented anemia and thrombocytopenia at 12 months of age. He was treated with corticosteroids and forwarded to our service for high blood pressure. However, the scans showed nephrotic proteinuria with renal involvement and hypoalbuminemia with direct Coombs negative. He developed anemia, thrombocytopenia, worsening of renal function and hypertension. Renal biopsy showed thrombotic microangiopathy (TMA). On the non-hemolytic anemia, thrombocytopenia and acute renal failure with histological substrate MAT, was diagnosed of aHUS. The patient received eculizumab excellent clinical and laboratory response. This case shows the importance of early diagnosis and treatment of the aHUS. Eculizumab is effective and keeps long-term remission, avoiding invasive measures such as plasmapheresis, which resolves only part of the picture.

Adesão ao tratamento imunossupressor no transplante renal / Compliance to immunosuppressive treatment in renal transplantation

Introdução: A não-adesão à terapia imunossupressora é um fenômeno que ocorre após o transplante renal em todas as faixas etárias, predominando na população pediátrica e nos adolescentes. O assunto é muito importante, pois implica em aumento do risco de rejeição aguda tardia e perda do enxerto. Objetivo: O objetivo deste estudo foi revisar a literatura a respeito da não-adesão ao tratamento medicamentoso após o transplante renal. Métodos: Foi realizado um levantamento bibliográfico do período de janeiro de 2000 a julho de 2007 nas plataformas de dados SciELO, PubMed, LILACS e MEDLINE utilizando descritores relacionados a esse tema. Resultados: Não há uma definição consensual do termo não-adesão. Os estudos disponíveis utilizaram uma variedade de instrumentos combinados para mensurar a adesão ao tratamento imunossupressor. Este fato certamente influenciou as diferenças na prevalência de não-adesão encontradas nos estudos, bem como na escolha das estratégias para evitá-la. Apesar dos autores concordarem que múltiplos fatores interferem na ocorrência de não-adesão em pacientes transplantados renais, existe discordância no que tange à qualidade desses fatores. Destacam-se os seguintes: idade do receptor, raça, gênero, nível socioeconômico, tipo de doador, relação médico-paciente, tempo de transplante, complexidade da doença e fatores psicossociais. Conclusão: Não está estabelecido um padrão-ouro para mensuração e prevenção da não-adesão. Entendê-la como um processo que perpassa por diferentes "saberes" parece um caminho a ser percorrido para melhor compreensão e atuação frente a esta relevante questão.

Introduction: Poor compliance with immunosuppressive treatment is seen after renal transplantation in patients of all ages, but it is more common in children and adolescents. This is an important matter because it increases the risk of late acute rejection and graft loss. The objective of this study was to review the literature on non-compliance with drug therapy after renal transplantation. Methods: SciELO, PubMed, LILACS, and MEDLINE databases from January 2000 to July 2007 were reviewed using descriptors related with this subject. Results: A widely accepted definition of non-compliance does not exist. The studies available used a variety of combined tools to measure compliance with immunosuppressive treatment. This, most likely, influenced the differences seen in the prevalence of non-compliance in patients after renal transplantation, as well as the choice of strategies to prevent it. Although the authors agreed that multiple factors interfere with the incidence of non-compliance after renal transplantation, they do not agree on the quality of those factors. Among those factors, we should mention: receptor age, race, gender, and socio-economical status, donor type, physician-patient relationship, time after transplantation, disease complexity, and psychosocial factors. Conclusion: A goldstandard method to measure and prevent non-compliance does not exist. The understanding that non-compliance is a multifactorial process seems to be the way to better understand and prevent this complex issue.

Co-interferências da farmacocinética dos inibidores de calcineurina em associação com micofenolato mofetil em pacientes transplantados renais / Interference of calcineurin inhibitors on the pharmakocinetics of mycophenolic acid in renal transplantation

O ácido micofenólico (MPA) é o metabólito ativo do micofenolato mofetil (MMF), um imunossupressor seletivo para linfócitos amplamente utilizado em transplantes. A exposição ao MPA na fase inicial pós-transplante renal está associada com menor incidência de rejeição aguda e com maior sobrevida do enxerto / Mycophenolic acid (MPA) is the active metabolite of mycophenolate mofetil (MMF), a selective lymphocyte anti-proliferative drug. It has been demonstrated that early adequate exposure to MPA is associated with less acute rejection and better long-term outcome in kidney transplantation. To the present, the recommended therapeutic range for MPA is an area under the concentration-time curve...

Seroprevalence of antibodies against varicella-zoster virus and response to the varicella vaccine in pediatric renal transplant patients.

The severity of varicella-zoster virus (VZV) in immunocompromised children, especially in those receiving renal transplants, is well known. However, the use of live attenuated virus vaccine in this population is controversial. This study aimed to: (i) assess the immunization status of pediatric renal transplant recipients at our center; (ii) determine the anti-VZV antibody titers in such patients; (iii) evaluate the response to VZV vaccine in seronegative children and in those who present low antibody titers (defined as <500 mAU/mL). Vaccinated children were monitored for adverse effects for 8 wk after vaccination. Fifty patients with a mean age of 13.7 yr (range, 3-17 yr) were enrolled. In 49, blood samples were collected and antibodies were screened using ELISA. Seropositivity to VZV was found in 43 (88%), and antibody titers were >/=500 mAU/mL in 37 (75.5%). Of the 12 children who were eligible for vaccination and had antibody titers <500 mAU/mL, one developed varicella before vaccination, two did not meet the inclusion criteria, and three parents refused the vaccination. In the six vaccinated children, there were no adverse reactions to the vaccine, and four (66.6%) responded with anti-VZV titers >/=500 mAU/mL 6-8 wk after vaccination. In conclusion, after renal transplantation, varicella vaccine is safe with a 66% rate of conversion to high antibody titers.