Rituximab em glomerulopatias primárias, 10 anos de experiência
Data
2022-05-15
Autores
Sales, Gabriel Teixeira Montezuma 
Orientadores
Kirsztajn, Gianna Mastroianni
Tipo
Dissertação de mestrado
Título da Revista
ISSN da Revista
Título de Volume
Resumo
NTRODUÇÃO: As glomerulopatias são a terceira causa de doença renal crônica em estágio terminal no Brasil e no mundo e a base do tratamento é a imunossupressão. O rituximab (RTX), anticorpo monoclonal contra linfócitos B (anti-CD20), apareceu nos últimos anos como opção terapêutica, mas com questões sobre segurança e eficiência ainda em aberto em algumas situações, como nas podocitopatias. OBJETIVOS: Descrever perfil clínico e laboratorial dos pacientes acompanhados no Ambulatório de Nefrites da UNIFESP com diagnóstico de glomerulopatia primária e que fizeram uso de RTX. Analisar variáveis associadas a resposta terapêutica e perfil de segurança da medicação. MÉTODOS: Estudo retrospectivo, observacional, longitudinal, realizado com revisão de prontuário. Os critérios de inclusão foram idade superior a 12 anos, laudo disponível da biópsia renal e uso de pelo menos 1 dose de RTX durante o acompanhamento; foram excluídos pacientes com suspeita de glomerulopatia secundária. RESULTADOS: Foram encontrados 45 pacientes dentro dos critérios de inclusão. A maioria foi do sexo masculino (62,2%), com média de idade no momento da infusão de 35,0 anos. A glomeruloesclerose segmentar e focal foi o padrão anatomopatológico em 55,6% dos casos, seguido por doença de lesões mínimas, com 26,7%. Ao considerar-se apenas as podocitopatias, encontramos taxa de remissão completa em T1 e T2 de 16,7% e 17,8%, respectivamente, enquanto a de remissão adaptada foi de 33,3% nos tempos analisados. Sensibilidade ao corticoide foi encontrada em 51,6% dos casos, e esses apresentaram algum tipo de remissão em 68,5% dos pacientes, enquanto os corticorresistentes não apresentaram remissão parcial ou completa e 21,4% preencheram critério de remissão adaptada. A presença de hipertensão arterial sistêmica e o uso prévio de inibidor de calcineurina teve valor preditivo de não resposta clínica. O evento adverso mais comum no período de até 1 ano após a infusão do RTX foi infecção, que ocorreu em 28,9% dos pacientes, seguido por rash (6,7%). Não houve identificação de óbitos no período de seguimento dos pacientes. Dois (4,17%) pacientes apresentaram piora progressiva da função renal, com início de terapia renal substitutiva 3 e 12 meses após a infusão. CONCLUSÕES: Tem-se demonstrado que o RTX é uma opção terapêutica nas glomerulopatias primárias, com perfil de segurança satisfatório, não sendo diferente na nossa população. Entretanto, ainda existe grande heterogeneidade de resposta de acordo com algumas características clínicas, tendo sido demonstrado principalmente a influência das variáveis resposta a corticoide, uso prévio de calcineurina, valor de albumina sérica pré infusão e presença de hipertensão.
INTRODUCTION: Membranoproliferative glomerulonephritis (MPGN) corresponds to approximately 7-10% of all cases of biopsied glomerulonephritis. It was previously classified into three categories according to the location of the immune deposits based upon electron microscopy findings. Currently, a new classification has been proposed based upon immunofluorescence microscopy (IF) findings. It is classified as being mediated by immune complexes, complement dysregulation or mechanisms not involving immunoglobulin or complement deposition. Such new classification intends to show different aspects of the disease. Its clinical presentation is quite variable, ranging from a slow and progressive course to rapidly progressive glomerulonephritis. Therefore, establishing characteristics that helps to better establish course and prognosis can provide a rationale for clinical investigation and disease-specific treatments. OBJECTIVES: The primary objectives of the study were: to determine the clinical, laboratory and histopathological characteristics of patients diagnosed with primary MPGN and to reclassify them based upon IF findings. The secondary objectives were to compare laboratory characteristics and renal prognosis in patients with histological diagnosis of primary and secondary MPGN; and evaluate the incidence of remission after therapy in primary MPGN. METHODS: This is an observational retrospective cohort study carried out in a single center (UNIFESP – EPM), based on the data collection from medical records of patients followed from 1996 to 2019. RESULTS: Out of 53 cases of MPGN, 36 (67.9%) were classified as primary and 17 (32.1%) as secondary MPGN. The average age of patients at the beginning of the follow-up was 38.8 years. Most patients were hypertensive (84.9%), had edema (88.7%) and anemia (84.9%); 33 (91.7%) of the patients classified as primary MPGN were reclassified as associated with immunocomplexes and 3 (8.3%) as associated with complement. The secondary MPGN group showed more frequent hematuria (p <0.001) and a higher prevalence of deposits of IgG (p = 0.019) and C1q (p = 0.003) when compared to the primary group. Regarding the outcome, final serum albumin <3g/dL and final P24h> 3.5g/24h were factors that drove the worst renal prognosis. CONCLUSIONS: According to the new classification based upon IF findings, the vast majority of MPGN cases were classified as being mediated by immune complexes, then there was not adequate number of cases to compose other comparison groups. There were few differences between primary and secondary MPGN in relation to their clinical and laboratory characteristics, standing out greater hematuria and higher prevalence of deposits of IgG and C1q in the secondary group, corroborating the importance of a classification based upon IF findings to distinguish these two groups.
INTRODUCTION: Membranoproliferative glomerulonephritis (MPGN) corresponds to approximately 7-10% of all cases of biopsied glomerulonephritis. It was previously classified into three categories according to the location of the immune deposits based upon electron microscopy findings. Currently, a new classification has been proposed based upon immunofluorescence microscopy (IF) findings. It is classified as being mediated by immune complexes, complement dysregulation or mechanisms not involving immunoglobulin or complement deposition. Such new classification intends to show different aspects of the disease. Its clinical presentation is quite variable, ranging from a slow and progressive course to rapidly progressive glomerulonephritis. Therefore, establishing characteristics that helps to better establish course and prognosis can provide a rationale for clinical investigation and disease-specific treatments. OBJECTIVES: The primary objectives of the study were: to determine the clinical, laboratory and histopathological characteristics of patients diagnosed with primary MPGN and to reclassify them based upon IF findings. The secondary objectives were to compare laboratory characteristics and renal prognosis in patients with histological diagnosis of primary and secondary MPGN; and evaluate the incidence of remission after therapy in primary MPGN. METHODS: This is an observational retrospective cohort study carried out in a single center (UNIFESP – EPM), based on the data collection from medical records of patients followed from 1996 to 2019. RESULTS: Out of 53 cases of MPGN, 36 (67.9%) were classified as primary and 17 (32.1%) as secondary MPGN. The average age of patients at the beginning of the follow-up was 38.8 years. Most patients were hypertensive (84.9%), had edema (88.7%) and anemia (84.9%); 33 (91.7%) of the patients classified as primary MPGN were reclassified as associated with immunocomplexes and 3 (8.3%) as associated with complement. The secondary MPGN group showed more frequent hematuria (p <0.001) and a higher prevalence of deposits of IgG (p = 0.019) and C1q (p = 0.003) when compared to the primary group. Regarding the outcome, final serum albumin <3g/dL and final P24h> 3.5g/24h were factors that drove the worst renal prognosis. CONCLUSIONS: According to the new classification based upon IF findings, the vast majority of MPGN cases were classified as being mediated by immune complexes, then there was not adequate number of cases to compose other comparison groups. There were few differences between primary and secondary MPGN in relation to their clinical and laboratory characteristics, standing out greater hematuria and higher prevalence of deposits of IgG and C1q in the secondary group, corroborating the importance of a classification based upon IF findings to distinguish these two groups.
Descrição
Citação
Sales, G.T.M. Rituximab nas glomerulopatias primárias: 10 anos de experiência. São Paulo, 2022. 76 f. Dissertação (Mestrado em Nefrologia) - Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, 2022.