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Ana Cristina Simões e Silvahttp://lattes.cnpq.br/4408599021040004Prof. Eduardo Araújo OliveiraProf. Olberes Vitor BragaDr.ª Mariana Affonso VasconcelosProf. Lucas Kangussuhttp://lattes.cnpq.br/4343855115466995Roberta da Silva Filha2022-07-22T13:42:15Z2022-07-22T13:42:15Z2021-08-13http://hdl.handle.net/1843/43537https://orcid.org/0000-0002-4695-0672Introdução: A síndrome nefrótica primária (SNP) é uma doença glomerular comum na faixa etária pediátrica, relacionada a alterações intrínsecas dos glomérulos sem causa estabelecida, que leva à proteinúria, edema, hipoalbuminemia e dislipidemia. Inúmeros fatores têm sido relacionados aos mecanismos de desenvolvimento e evolução da doença como alterações dos componentes da barreira de filtração glomerular, modificações no sistema imune e atuação do sistema renina angiotensina (SRA). No entanto, a fisiopatologia da doença ainda não está elucidada e persistem diversas questões referentes ao tratamento mais apropriado. Objetivos: Avaliar a atuação do SRA, das moléculas inflamatórias, adipocinas, hormônios do metabolismo e marcadores de função endotelial em pacientes pediátricos com SN primária. Métodos: Foi realizado um estudo transversal que incluiu 33 crianças e adolescentes com SNP em remissão parcial e completa. As mensurações dos biomarcadores foram comparadas entre os pacientes e indivíduos saudáveis (grupo controle), pareados por idade e sexo. Os biomarcadores foram relacionados às variáveis clínicas e laboratoriais. Resultados: Em nosso primeiro estudo original, verificamos que as concentrações urinárias de Ang II, Ang-(1-7), ECA e MCP-1 encontravam-se aumentadas nos pacientes com SNP em comparação ao grupo controle. Por outro lado, os níveis urinários de ECA2 eram significativamente menores nos pacientes com SNP e correlacionavam negativamente com a proteinúria. No segundo estudo, os níveis urinários de leptina e as concentrações plasmáticas de resistina e grelina estavam significativamente aumentadas em relação ao grupo controle. Em contrapartida as concentrações urinárias de adiponectina e PAI-1 foram menores nos pacientes SN quando comparados aos controles. Conclusão: As moléculas do SRA, as quimiocinas, as adipocinas, os hormônios do metabolismo e marcadores de função endotelial foram encontrados em diferentes concentrações em pacientes com SNP comparados ao grupo controle, sugerindo que essas moléculas participam da fisiopatologia e da progressão da lesão renal.Introduction: Primary nephrotic syndrome (PNS) is a common glomerular disease in the pediatric age group, related to intrinsic changes in the glomeruli without an established cause, which leads to proteinuria, edema, hypoalbuminemia and dyslipidemia. Numerous factors have been related to the mechanisms of development and evolution of the disease, including changes in the components of the glomerular filtration barrier, alterations in the immune system and the effects of the renin angiotensin system (RAS). However, the pathophysiology of the disease remains to be elucidated and several questions regarding the most appropriate treatment persist. Objectives: To evaluate the role of RAS, inflammatory molecules, adipokines, metabolism hormones and endothelial function markers in pediatric patients with primary NS. Methods: This cross-sectional study included 33 children and adolescents with SNP in partial and complete remission. Biomarker measurements were compared between patients and healthy individuals (control group), matched for age and sex. Biomarkers were related to clinical and laboratory variables. Results: In our first original study, we found that urinary concentrations of Ang II, Ang-(1-7), ACE and MCP-1 were increased in patients with PNS compared to the control group. On the other hand, urinary ACE2 levels were significantly lower in patients with PNS and negatively correlated with proteinuria. In the second study, urinary leptin levels and plasma concentrations of resistin and ghrelin were significantly increased compared to the control group. In contrast, urinary adiponectin and PAI-1 concentrations were lower in PNS patients when compared to controls. Conclusion: RAS molecules, chemokines, adipokines, metabolism hormones and endothelial function markers were found in different concentrations in patients with PNS compared to the control group, suggesting that these molecules participate in the pathophysiology and progression of renal damage.CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorporUniversidade Federal de Minas GeraisPrograma de Pós-Graduação em Ciências da Saúde - Saúde da Criança e do AdolescenteUFMGBrasilMEDICINA - FACULDADE DE MEDICINASíndrome NefróticaAdipocinasBiomarcadoresSistema Renina-AngiotensinaSíndrome NefróticaSRAMoléculas inflamatóriasAdipocinasMarcadores metabólicosMarcadores de função endotelialAvaliação de potenciais biomarcadores na síndrome nefrótica primária em pacientes pediátricos.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGORIGINALTese.pdfTese.pdfapplication/pdf2536450https://repositorio.ufmg.br/bitstream/1843/43537/1/Tese.pdff4b110762a8f5160c48be33b2330f544MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-82118https://repositorio.ufmg.br/bitstream/1843/43537/2/license.txtcda590c95a0b51b4d15f60c9642ca272MD521843/435372022-07-22 10:42:15.831oai:repositorio.ufmg.br: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ório InstitucionalPUBhttps://repositorio.ufmg.br/oaiopendoar:2022-07-22T13:42:15Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false
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