Avaliação de biomarcadores em pacientes com podocitopatias pediátricas

Detalhes bibliográficos
Autor(a) principal: PEREIRA, Lívia Helena de Morais
Data de Publicação: 2018
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da UFTM
Texto Completo: http://bdtd.uftm.edu.br/handle/tede/650
Resumo: Introdução: Doença de Lesões Mínimas (DLM) e Glomeruloesclerose Segmentar e Focal (GESF) são podocitopatias, um dos principais grupos de glomerulopatias da infância. Há controvérsias se são lesões glomerulares distintas ou manifestações diversas dentro do mesmo espectro de doenças, pois podem apresentar curso clínico semelhante e podem ter evoluções variadas, indo da remissão à falha terapêutica. O CD80, o uPAR e algumas proteínas do diafragma slit nos podócitos podem estar alterados no glomérulo de pacientes com GESF e DLM e podem funcionar como biomarcadores e/ou marcador de prognóstico dessas podocitopatias em biópsias renais. Objetivo: Avaliar o potencial diagnóstico de CD80, uPAR, nefrina e podocina para DLM e GESF na biópsia renal pediátrica, detectar o possível potencial prognóstico dos marcadores e avaliar a evolução clínica desses pacientes. Metodologia: Foram selecionadas biópsias renais de 50 crianças, de 2 a 18 anos, com diagnóstico de DLM (29) e GESF (21). O grupo controle foi composto por 15 casos de autópsias pediátricas, sem alteração da função renal. Foram avaliadas as expressões in situ de WT1, Nefrina, Podocina, CD80 e uPAR por meio da técnica de imunoperoxidase. Foi utilizada curva ROC para análise de desempenho diagnóstico dos biomarcadores. Foi avaliado também a evolução clínica e a terapia medicamentosa de 22 crianças, seis anos após o diagnóstico. Os biomarcadores foram avaliados em relação a evolução clínica. Resultado: Pacientes com DLM e GESF expressaram menos WT1 e nefrina na biópsia renal que pacientes do grupo controle (p≤0,0001; F=19,35 e p<0,0001; H=21,54). Pacientes com GESF expressaram menos nefrina e podocina que os casos controle (p<0,0359; H=6,655) e houve correlação positiva e significativa entre nefrina e podocina (p=0,0026; rS=0,6502). Não houve diferença entre os grupos, quanto a expressão de CD80 (p=0,1895; H=3,327). Casos de GESF expressaram mais uPAR que casos controle e DLM (p=0,0019; H=12,57). A podocina apresentou sensibilidade de 73,3% e especificidade de 86,7% (p=0,006) e uPAR teve sensibilidade de 78,9% e especificidade de 73,3% (p=0,004) nas biópsias de pacientes com GESF. A maioria dos pacientes apresentou algum grau de remissão do quadro inicial após o tratamento (64%). A expressão de uPAR no momento do diagnóstico foi significativamente maior entre os pacientes que evoluíram com resistência terapêutica em relação aos que evoluíram com remissão (p=0,04; t=0,2524). Conclusão: Podocina e uPAR são bons marcadores para GESF. Maior expressão de uPAR em casos de podocitopatias é fator preditor de resistência terapêutica. Esses achados sugerem que podocina e uPAR podem ser usados como biomarcadores na rotina da biópsia renal nos casos de podocitopatias em que alesão (esclerose) não for amostrada, e que o uPAR pode auxiliar na determinação do prognóstico desses pacientes.
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spelling Avaliação de biomarcadores em pacientes com podocitopatias pediátricasBiomarcadores.Biópsia renal pediátrica.Podocina.uPAR.Resistência Terapêutica.Podocitopatias.Biomarkers.Renal biopsy.Podocin.uPAR.Therapeutic resistence.Podocytopathies.Anatomia Patológica e Patologia ClínicaIntrodução: Doença de Lesões Mínimas (DLM) e Glomeruloesclerose Segmentar e Focal (GESF) são podocitopatias, um dos principais grupos de glomerulopatias da infância. Há controvérsias se são lesões glomerulares distintas ou manifestações diversas dentro do mesmo espectro de doenças, pois podem apresentar curso clínico semelhante e podem ter evoluções variadas, indo da remissão à falha terapêutica. O CD80, o uPAR e algumas proteínas do diafragma slit nos podócitos podem estar alterados no glomérulo de pacientes com GESF e DLM e podem funcionar como biomarcadores e/ou marcador de prognóstico dessas podocitopatias em biópsias renais. Objetivo: Avaliar o potencial diagnóstico de CD80, uPAR, nefrina e podocina para DLM e GESF na biópsia renal pediátrica, detectar o possível potencial prognóstico dos marcadores e avaliar a evolução clínica desses pacientes. Metodologia: Foram selecionadas biópsias renais de 50 crianças, de 2 a 18 anos, com diagnóstico de DLM (29) e GESF (21). O grupo controle foi composto por 15 casos de autópsias pediátricas, sem alteração da função renal. Foram avaliadas as expressões in situ de WT1, Nefrina, Podocina, CD80 e uPAR por meio da técnica de imunoperoxidase. Foi utilizada curva ROC para análise de desempenho diagnóstico dos biomarcadores. Foi avaliado também a evolução clínica e a terapia medicamentosa de 22 crianças, seis anos após o diagnóstico. Os biomarcadores foram avaliados em relação a evolução clínica. Resultado: Pacientes com DLM e GESF expressaram menos WT1 e nefrina na biópsia renal que pacientes do grupo controle (p≤0,0001; F=19,35 e p<0,0001; H=21,54). Pacientes com GESF expressaram menos nefrina e podocina que os casos controle (p<0,0359; H=6,655) e houve correlação positiva e significativa entre nefrina e podocina (p=0,0026; rS=0,6502). Não houve diferença entre os grupos, quanto a expressão de CD80 (p=0,1895; H=3,327). Casos de GESF expressaram mais uPAR que casos controle e DLM (p=0,0019; H=12,57). A podocina apresentou sensibilidade de 73,3% e especificidade de 86,7% (p=0,006) e uPAR teve sensibilidade de 78,9% e especificidade de 73,3% (p=0,004) nas biópsias de pacientes com GESF. A maioria dos pacientes apresentou algum grau de remissão do quadro inicial após o tratamento (64%). A expressão de uPAR no momento do diagnóstico foi significativamente maior entre os pacientes que evoluíram com resistência terapêutica em relação aos que evoluíram com remissão (p=0,04; t=0,2524). Conclusão: Podocina e uPAR são bons marcadores para GESF. Maior expressão de uPAR em casos de podocitopatias é fator preditor de resistência terapêutica. Esses achados sugerem que podocina e uPAR podem ser usados como biomarcadores na rotina da biópsia renal nos casos de podocitopatias em que alesão (esclerose) não for amostrada, e que o uPAR pode auxiliar na determinação do prognóstico desses pacientes.Introduction: Minimal Change Disease (MCD) and Focal and Segmental Glomerulosclerosis (FSGS) are podocytopathies, one of the main groups of glomerulopathies in childhood. It is controversial whether they are distinct glomerular lesions or diverse manifestations within the same spectrum of diseases, since they may present a similar clinical course and may have varying outcomes ranging from remission to therapeutic failure. CD80, uPAR and some podocyte slit diaphragm proteins may be altered in glomerulus of patients with FSGS and MCD and may function as podocytopathy biomarkers and / or prognostic markers in renal biopsies. Objective: To evaluate the diagnostic potential of CD80, uPAR, nephrin and podocin for MCD and FSGS in renal pediatric biopsies and to detect the potential of uPAR as prognostic marker. Methods: Renal biopsies of 50 children with age ranging from two to 18 years old, with diagnosis of MCD (29) and FSGS (21) were selected. Control group consisted of 15 renal fragments from pediatric autopsies, with no change in renal function. In situ expressions of WT1, Nephrin, Podocin, CD80 and uPAR were evaluated by immunoperoxidase technique. ROC curve was used to analyze biomarkers diagnostic performance. Clinical outcome and drug therapy of 22 children, six years after diagnosis, were also evaluated. Biomarkers were evaluated regarding clinical outcome. Results: Patients with MCD and FSGS had decreased expression of WT1 and nephrin on renal biopsies comparing to control group (p≤0,0001, F = 19.35 and p <0.0001; H = 21.54). Patients with FSGS showed less nephrin and podocin than control cases (p <0.0359; H = 6.655) and there was a positive and significant correlation between nephrin and podocin (p = 0.0026, rS = 0.6502). There was no difference between groups regarding CD80 expression (p = 0.1895; H = 3.327). FSGS cases expressed more uPAR than control and MCD cases (p = 0.0019; H = 12.57). Podocin presented sensitivity of 73.3% and specificity of 86.7% (p = 0.006) and uPAR had sensitivity of 78.9% and specificity of 73.3% (p = 0.004) in FSGS biopsies. Most patients presented some degree of remission of initial condition after treatment (64%). UPAR expression at the time of diagnosis was significantly higher among patients who evolved with therapeutic resistance than those who evolved with remission (p = 0.04; t = 0.2524). Conclusion: Podocin and uPAR are good markers for FSGS. Higher uPAR expression in cases of podocytopathies is a predictor of therapeutic resistance. These findings suggest that podocin and uPAR can be routinely used as biomarkers in renal biopsies from cases of podocytopathies in which the lesion (sclerosis) is not sampled and that uPAR may assist in determining prognosisCoordenação de Aperfeiçoamento de Pessoal de Nível SuperiorConselho Nacional de Desenvolvimento Científico e TecnológicoFundação de Ensino e Pesquisa de UberabaUniversidade Federal do Triângulo MineiroInstituto de Ciências da Saúde - ICS::Programa de Pós-Graduação em Ciências da SaúdeBrasilUFTMPrograma de Pós-Graduação em Ciências da SaúdeSILVA, Juliana Reis Machado e06911408636http://lattes.cnpq.br/5289363102869037REIS, Marlene Antônia dos51733277668http://lattes.cnpq.br/3194932402580523PEREIRA, Lívia Helena de Morais2019-05-16T18:37:41Z2018-06-29info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisapplication/pdfapplication/pdfPEREIRA, Lívia Helena de Morais. 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dc.title.none.fl_str_mv Avaliação de biomarcadores em pacientes com podocitopatias pediátricas
title Avaliação de biomarcadores em pacientes com podocitopatias pediátricas
spellingShingle Avaliação de biomarcadores em pacientes com podocitopatias pediátricas
PEREIRA, Lívia Helena de Morais
Biomarcadores.
Biópsia renal pediátrica.
Podocina.
uPAR.
Resistência Terapêutica.
Podocitopatias.
Biomarkers.
Renal biopsy.
Podocin.
uPAR.
Therapeutic resistence.
Podocytopathies.
Anatomia Patológica e Patologia Clínica
title_short Avaliação de biomarcadores em pacientes com podocitopatias pediátricas
title_full Avaliação de biomarcadores em pacientes com podocitopatias pediátricas
title_fullStr Avaliação de biomarcadores em pacientes com podocitopatias pediátricas
title_full_unstemmed Avaliação de biomarcadores em pacientes com podocitopatias pediátricas
title_sort Avaliação de biomarcadores em pacientes com podocitopatias pediátricas
author PEREIRA, Lívia Helena de Morais
author_facet PEREIRA, Lívia Helena de Morais
author_role author
dc.contributor.none.fl_str_mv SILVA, Juliana Reis Machado e
06911408636
http://lattes.cnpq.br/5289363102869037
REIS, Marlene Antônia dos
51733277668
http://lattes.cnpq.br/3194932402580523
dc.contributor.author.fl_str_mv PEREIRA, Lívia Helena de Morais
dc.subject.por.fl_str_mv Biomarcadores.
Biópsia renal pediátrica.
Podocina.
uPAR.
Resistência Terapêutica.
Podocitopatias.
Biomarkers.
Renal biopsy.
Podocin.
uPAR.
Therapeutic resistence.
Podocytopathies.
Anatomia Patológica e Patologia Clínica
topic Biomarcadores.
Biópsia renal pediátrica.
Podocina.
uPAR.
Resistência Terapêutica.
Podocitopatias.
Biomarkers.
Renal biopsy.
Podocin.
uPAR.
Therapeutic resistence.
Podocytopathies.
Anatomia Patológica e Patologia Clínica
description Introdução: Doença de Lesões Mínimas (DLM) e Glomeruloesclerose Segmentar e Focal (GESF) são podocitopatias, um dos principais grupos de glomerulopatias da infância. Há controvérsias se são lesões glomerulares distintas ou manifestações diversas dentro do mesmo espectro de doenças, pois podem apresentar curso clínico semelhante e podem ter evoluções variadas, indo da remissão à falha terapêutica. O CD80, o uPAR e algumas proteínas do diafragma slit nos podócitos podem estar alterados no glomérulo de pacientes com GESF e DLM e podem funcionar como biomarcadores e/ou marcador de prognóstico dessas podocitopatias em biópsias renais. Objetivo: Avaliar o potencial diagnóstico de CD80, uPAR, nefrina e podocina para DLM e GESF na biópsia renal pediátrica, detectar o possível potencial prognóstico dos marcadores e avaliar a evolução clínica desses pacientes. Metodologia: Foram selecionadas biópsias renais de 50 crianças, de 2 a 18 anos, com diagnóstico de DLM (29) e GESF (21). O grupo controle foi composto por 15 casos de autópsias pediátricas, sem alteração da função renal. Foram avaliadas as expressões in situ de WT1, Nefrina, Podocina, CD80 e uPAR por meio da técnica de imunoperoxidase. Foi utilizada curva ROC para análise de desempenho diagnóstico dos biomarcadores. Foi avaliado também a evolução clínica e a terapia medicamentosa de 22 crianças, seis anos após o diagnóstico. Os biomarcadores foram avaliados em relação a evolução clínica. Resultado: Pacientes com DLM e GESF expressaram menos WT1 e nefrina na biópsia renal que pacientes do grupo controle (p≤0,0001; F=19,35 e p<0,0001; H=21,54). Pacientes com GESF expressaram menos nefrina e podocina que os casos controle (p<0,0359; H=6,655) e houve correlação positiva e significativa entre nefrina e podocina (p=0,0026; rS=0,6502). Não houve diferença entre os grupos, quanto a expressão de CD80 (p=0,1895; H=3,327). Casos de GESF expressaram mais uPAR que casos controle e DLM (p=0,0019; H=12,57). A podocina apresentou sensibilidade de 73,3% e especificidade de 86,7% (p=0,006) e uPAR teve sensibilidade de 78,9% e especificidade de 73,3% (p=0,004) nas biópsias de pacientes com GESF. A maioria dos pacientes apresentou algum grau de remissão do quadro inicial após o tratamento (64%). A expressão de uPAR no momento do diagnóstico foi significativamente maior entre os pacientes que evoluíram com resistência terapêutica em relação aos que evoluíram com remissão (p=0,04; t=0,2524). Conclusão: Podocina e uPAR são bons marcadores para GESF. Maior expressão de uPAR em casos de podocitopatias é fator preditor de resistência terapêutica. Esses achados sugerem que podocina e uPAR podem ser usados como biomarcadores na rotina da biópsia renal nos casos de podocitopatias em que alesão (esclerose) não for amostrada, e que o uPAR pode auxiliar na determinação do prognóstico desses pacientes.
publishDate 2018
dc.date.none.fl_str_mv 2018-06-29
2019-05-16T18:37:41Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
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status_str publishedVersion
dc.identifier.uri.fl_str_mv PEREIRA, Lívia Helena de Morais. Avaliação de biomarcadores em pacientes com podocitopatias pediátricas. 2018. 89f. Tese (Doutorado em Ciências da Saúde) - Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal do Triângulo Mineiro, Uberaba, 2018.
http://bdtd.uftm.edu.br/handle/tede/650
identifier_str_mv PEREIRA, Lívia Helena de Morais. Avaliação de biomarcadores em pacientes com podocitopatias pediátricas. 2018. 89f. Tese (Doutorado em Ciências da Saúde) - Programa de Pós-Graduação em Ciências da Saúde, Universidade Federal do Triângulo Mineiro, Uberaba, 2018.
url http://bdtd.uftm.edu.br/handle/tede/650
dc.language.iso.fl_str_mv por
language por
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Instituto de Ciências da Saúde - ICS::Programa de Pós-Graduação em Ciências da Saúde
Brasil
UFTM
Programa de Pós-Graduação em Ciências da Saúde
publisher.none.fl_str_mv Universidade Federal do Triângulo Mineiro
Instituto de Ciências da Saúde - ICS::Programa de Pós-Graduação em Ciências da Saúde
Brasil
UFTM
Programa de Pós-Graduação em Ciências da Saúde
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