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Doctoral Thesis
DOI
https://doi.org/10.11606/T.17.2022.tde-10042023-090522
Document
Author
Full name
Renata Valente Lisboa
Institute/School/College
Knowledge Area
Date of Defense
Published
Ribeirão Preto, 2022
Supervisor
Committee
Júnior, Paulo Louzada (President)
Dantas, Marcio
Carvalho, Luciana Martins de
Souza, Viviane Angelina de
Title in Portuguese
Avaliação sérica da survivina e do Fator de Crescimento Endotelial Vascular (VEGF) em pacientes com nefrite lúpica
Keywords in Portuguese
Biomarcadores
Fator de Crescimento Endotelial Vascular
Nefrite lúpica
Survivina
Abstract in Portuguese
Introdução: Lupus eritematoso sistêmico (LES) é uma doença inflamatória autoimune na qual o acometimento renal (NL) atinge até 50% dos pacientes, tendo aspectos sobre seu desenvolvimento e acompanhamento ainda pouco esclarecidos. A análise clínica tem um importante papel, entretanto, a biópsia renal é o padrão ouro para NL. Novos biomarcadores poderiam auxiliar no diagnóstico e manejo não-invasivo da NL, e dentre os candidatos estudamos a Survivina e o Fator de Crescimento Endotelial Vascular (VEGF). Objetivo: Avaliar se Survivina e VEGF estão associados com atividade de doença, classe histológica e resposta à terapia com ciclofosfamida na NL. Avaliar o comportamento da albumina e do sedimento urinário na NL. Pacientes e Métodos: Foram avaliados, em seguimento longitudinal, 97 pacientes com NL ativa antes e após tratamento com pulsoterapia. Outros 200 pacientes lúpicos foram divididos em quatro grupos: com e sem nefrite lúpica, em atividade e em remissão da doença, e comparados entre si e ao grupo de voluntários sadios. A dosagem de Survivina e VEGF foi realizada por método de ELISA em amostras de soro previamente coletadas. Análise estatística feita no IBM SPSS versão 21.0 e o valor de p≤0,05 foi adotado para significância estatística. Resultados: Os pacientes lúpicos apresentaram níveis reduzidos de survivina e níveis aumentados de VEGF quando comparados a indivíduos saudáveis. Após a pulsoterapia ocorreu redução significativa dos níveis de survivina, sem diferença na análise envolvendo VEGF. Não houve poder discriminativo dos pacientes em atividade daqueles em remissão, bem como do acometimento renal ou sua classe histológica, apesar das diferenças. A presença de hematúria e leucocitúria no sedimento urinário foram mais prevalentes naqueles pacientes com classe proliferativa da NL. Os níveis de albumina sérica aumentaram significativamente após pulsoterapia, com comportamento similar às frações do complemento na NL. Conclusão: Survivina e VEGF não foram capazes de atuar como biomarcadores de resposta terapêutica nem de evidenciar o acometimento renal nos pacientes com LES.
Title in English
Serum assessment of survivin and Vascular Endothelial Growth Factor (VEGF) in patients with lupus nephritis
Keywords in English
Biomarkers
Lupus nephritis
Survivin
Vascular Endothelial Growth Factor
Abstract in English
Introduction: Systemic lupus erythematosus (SLE) is an autoimmune inflammatory disease in which renal involvement (LN) affects up to 50% of patients, with aspects of its development and follow-up still unclear. Clinical analysis plays an important role, however, renal biopsy is the gold standard for LN. New biomarkers could help in the diagnosis and non-invasive management of LN, and among the candidates we studied Survivin and Vascular Endothelial Growth Factor (VEGF). Objective: To assess whether Survivin and VEGF are associated with disease activity, histological class and response to cyclophosphamide therapy in LN. To evaluate the behavior of albumin and urinary sediment in LN. Patients and Methods: In longitudinal follow-up, 97 patients with active LN were evaluated before and after treatment with pulse therapy. Another 200 lupus patients were divided into four groups: with and without lupus nephritis, in activity and in disease remission, and compared with each other and with the group of healthy volunteers. Survivin and VEGF dosage was performed by ELISA method in previously collected serum samples. Statistical analysis performed in IBM SPSS version 21.0 and the value of p≤0.05 was adopted for statistical significance. Results: SLE patients had reduced levels of survivin and increased levels of VEGF when compared to healthy subjects. After pulse therapy, there was a significant reduction in survivin levels, with no difference in the analysis involving VEGF. There was no discriminative power between active patients and those in remission, as well a renal involvement or histological class, despite the differences. The presence of hematuria and leukocyturia in the urinary sediment were more prevalent in those patients with LN proliferative class. Serum albumin levels increased significantly after pulse therapy, with a similar behavior to the complement fractions in LN. Conclusion: Survivin and VEGF were not able to act as biomarkers of therapeutic response or to evidence renal involvement in patients with SLE.
 
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Publishing Date
2023-04-13
 
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