Novos biomarcadores de função renal não convencionais em pacientes com hemoglobinúria paroxística noturna

Detalhes bibliográficos
Ano de defesa: 2019
Autor(a) principal: Pro, Juan Daniel Zuñiga
Orientador(a): Daher, Elizabeth de Francesco
Banca de defesa: Não Informado pela instituição
Tipo de documento: Dissertação
Tipo de acesso: Acesso aberto
Idioma: por
Instituição de defesa: Não Informado pela instituição
Programa de Pós-Graduação: Não Informado pela instituição
Departamento: Não Informado pela instituição
País: Não Informado pela instituição
Palavras-chave em Português:
Link de acesso: http://www.repositorio.ufc.br/handle/riufc/47684
Resumo: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare chronic acquired hemolytic disease, of which the pathophysiology of renal dysfunction is not well understood. Objectives:To evaluate the importance of new biomarkersof early renal injury in patients with PNH. Methods:A cross-sectional, observational and analytical case-control study was conducted with 17 PNH patients from the HUWC hematology outpatient clinic. After confirmation of the diagnosis by peripheral blood flowcytometry, random urine and blood samples were collected. Clinical and renal parameters associated with PNH were evaluated. For renal function analysis the glomerular filtration rate (eGFR) was estimated using the CKD-EPI formula. Two renal biomarkerswere evaluated: urinary KIM-1 (uKIM-1) and urinary MCP-1 (uMCP-1), which were quantified using the immunoassay method (ELISA). Statistical comparisons and correlations were performed to assess the role of renal biomarkers in detecting subclinical renal changes in PNH. Results:Patients with PNH had noticeablehematological disorders and signs of intravascular hemolytic anemia. The uMCP-1 levels were significantly higher compared to the control group (p = 0.017) and showed positive correlations with sodium excretion fraction (p = 0.004), chloride excretion fraction (p = 0.008),and inverse correlationwith uric acid (p = 0.016). Regarding uKIM-1 levels, no relevant statisticalsignificance wasfound between the two groups (p = 0.65). Conclusion:No clinically evident renal dysfunction was observed using the traditional markers of renal function. However, uMCP-1 showed elevated levels in PNH patients, who may have renal damage to the proximal tubule epithelial cells due to inflammatory processes in the intermediate space between the tubules (interstitial nephritis). This result suggests that uMCP-1 could represent a useful biomarker for early detection of renal dysfunction. The lack of significant results with the uKIM-1 biomarker may be attributableto the absenceof renal injury of ischemic origin due to the importantreduction in thrombotic events following
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spelling Pro, Juan Daniel ZuñigaDaher, Elizabeth de Francesco2019-11-12T17:17:18Z2019-11-12T17:17:18Z2019-08-29PRO, J. D. Z. Novos biomarcadores de função renal não convencionais em pacientes com hemoglobinúria paroxística noturna. 2018. 68 f. Dissertação (Mestrado em Ciências Médicas) - Faculdade de Medicina, Universidade Federal do Ceará, 2018.http://www.repositorio.ufc.br/handle/riufc/47684Paroxysmal nocturnal hemoglobinuria (PNH) is a rare chronic acquired hemolytic disease, of which the pathophysiology of renal dysfunction is not well understood. Objectives:To evaluate the importance of new biomarkersof early renal injury in patients with PNH. Methods:A cross-sectional, observational and analytical case-control study was conducted with 17 PNH patients from the HUWC hematology outpatient clinic. After confirmation of the diagnosis by peripheral blood flowcytometry, random urine and blood samples were collected. Clinical and renal parameters associated with PNH were evaluated. For renal function analysis the glomerular filtration rate (eGFR) was estimated using the CKD-EPI formula. Two renal biomarkerswere evaluated: urinary KIM-1 (uKIM-1) and urinary MCP-1 (uMCP-1), which were quantified using the immunoassay method (ELISA). Statistical comparisons and correlations were performed to assess the role of renal biomarkers in detecting subclinical renal changes in PNH. Results:Patients with PNH had noticeablehematological disorders and signs of intravascular hemolytic anemia. The uMCP-1 levels were significantly higher compared to the control group (p = 0.017) and showed positive correlations with sodium excretion fraction (p = 0.004), chloride excretion fraction (p = 0.008),and inverse correlationwith uric acid (p = 0.016). Regarding uKIM-1 levels, no relevant statisticalsignificance wasfound between the two groups (p = 0.65). Conclusion:No clinically evident renal dysfunction was observed using the traditional markers of renal function. However, uMCP-1 showed elevated levels in PNH patients, who may have renal damage to the proximal tubule epithelial cells due to inflammatory processes in the intermediate space between the tubules (interstitial nephritis). This result suggests that uMCP-1 could represent a useful biomarker for early detection of renal dysfunction. The lack of significant results with the uKIM-1 biomarker may be attributableto the absenceof renal injury of ischemic origin due to the importantreduction in thrombotic events followingA hemoglobinúria paroxística noturna (HPN) é uma doença hemolítica crônica adquirida classificada como rara, da qual a fisiopatologia da disfunção renal ainda não é bem entendida. Objetivos:Avaliar a importânciade novos biomarcadores de lesão renal precoce em pacientes com HPN. Métodos:Foi realizado um estudotransversalde caso-controle, observacional e analíticocom 17 pacientes com HPNdo ambulatório de hematologia do HUWC. Após a confirmação do diagnóstico pela citometria de fluxode sangue periférico, foram coletadas amostras aleatórias de urina e sangue. Foramavaliados parâmetros clínicos e renais associados à HPN. Para análise da função renal o ritmo de filtração glomerular (RFGe) foi estimado usando a fórmula CKD-EPI. Dois biomarcadores renais foram avaliados: KIM-1 urinário (uKIM-1) e MCP-1 urinário (uMCP-1), os quais foram quantificados utilizando o método de imunoensaio (ELISA). Foram realizadas comparações e correlações estatísticas para avaliar o papel dos biomarcadores renais para a detecção de alterações renais subclínicas na HPN. Resultados:Os pacientes com HPN apresentaram importantes distúrbios hematológicos e sinais de anemia hemolítica intravascular. Os níveis de uMCP-1 foram significativamente maiores em comparação com o grupo controle (p=0.017) e apresentou correlações positivas com a fração de excreção de sódio (p=0.004), fração de excreção de cloreto (p=0.008) e correlação inversa com o ácido úrico (p=0.016). Em relação aos níveis de uKIM-1, não foi encontrada significância estatisticamente relevante entre os dois grupos (p=0.65). Conclusão: Não foi observada disfunção renal clinicamente evidente utilizando os marcadores tradicionais de função renal. Porém,o uMCP-1 apresentou níveis elevados nos pacientes com HPN, quepodem apresentar danos renaisnascélulas epiteliais do túbulo proximaldevido a processos inflamatórios no espaço intermediário entre os túbulos (nefrite intersticial). Esse resultadosugereque o uMCP-1 poderia representar um biomarcador útil para a detecção precoce de disfunção renal. A falta de resultados significativos com o biomarcador uKIM-1 pode ser devido à ausência de lesão renal de origem isquêmica, devido à redução significativa de eventos trombóticosapós o uso de eculizumabe.Hemoglobinúria ParoxísticaLesão Renal AgudaBiomarcadoresÁcido 2-Metil-4-clorofenoxiacéticoNovos biomarcadores de função renal não convencionais em pacientes com hemoglobinúria paroxística noturnainfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFCinfo:eu-repo/semantics/openAccessORIGINAL2019_dis_jdzp.pdf2019_dis_jdzp.pdfapplication/pdf2682368http://repositorio.ufc.br/bitstream/riufc/47684/1/2019_dis_jdzp.pdfaa2b7aa6ae3b1db68017e716890af5b4MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/47684/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52riufc/476842022-03-04 16:10:22.093oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2022-03-04T19:10:22Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Novos biomarcadores de função renal não convencionais em pacientes com hemoglobinúria paroxística noturna
title Novos biomarcadores de função renal não convencionais em pacientes com hemoglobinúria paroxística noturna
spellingShingle Novos biomarcadores de função renal não convencionais em pacientes com hemoglobinúria paroxística noturna
Pro, Juan Daniel Zuñiga
Hemoglobinúria Paroxística
Lesão Renal Aguda
Biomarcadores
Ácido 2-Metil-4-clorofenoxiacético
title_short Novos biomarcadores de função renal não convencionais em pacientes com hemoglobinúria paroxística noturna
title_full Novos biomarcadores de função renal não convencionais em pacientes com hemoglobinúria paroxística noturna
title_fullStr Novos biomarcadores de função renal não convencionais em pacientes com hemoglobinúria paroxística noturna
title_full_unstemmed Novos biomarcadores de função renal não convencionais em pacientes com hemoglobinúria paroxística noturna
title_sort Novos biomarcadores de função renal não convencionais em pacientes com hemoglobinúria paroxística noturna
author Pro, Juan Daniel Zuñiga
author_facet Pro, Juan Daniel Zuñiga
author_role author
dc.contributor.author.fl_str_mv Pro, Juan Daniel Zuñiga
dc.contributor.advisor1.fl_str_mv Daher, Elizabeth de Francesco
contributor_str_mv Daher, Elizabeth de Francesco
dc.subject.por.fl_str_mv Hemoglobinúria Paroxística
Lesão Renal Aguda
Biomarcadores
Ácido 2-Metil-4-clorofenoxiacético
topic Hemoglobinúria Paroxística
Lesão Renal Aguda
Biomarcadores
Ácido 2-Metil-4-clorofenoxiacético
description Paroxysmal nocturnal hemoglobinuria (PNH) is a rare chronic acquired hemolytic disease, of which the pathophysiology of renal dysfunction is not well understood. Objectives:To evaluate the importance of new biomarkersof early renal injury in patients with PNH. Methods:A cross-sectional, observational and analytical case-control study was conducted with 17 PNH patients from the HUWC hematology outpatient clinic. After confirmation of the diagnosis by peripheral blood flowcytometry, random urine and blood samples were collected. Clinical and renal parameters associated with PNH were evaluated. For renal function analysis the glomerular filtration rate (eGFR) was estimated using the CKD-EPI formula. Two renal biomarkerswere evaluated: urinary KIM-1 (uKIM-1) and urinary MCP-1 (uMCP-1), which were quantified using the immunoassay method (ELISA). Statistical comparisons and correlations were performed to assess the role of renal biomarkers in detecting subclinical renal changes in PNH. Results:Patients with PNH had noticeablehematological disorders and signs of intravascular hemolytic anemia. The uMCP-1 levels were significantly higher compared to the control group (p = 0.017) and showed positive correlations with sodium excretion fraction (p = 0.004), chloride excretion fraction (p = 0.008),and inverse correlationwith uric acid (p = 0.016). Regarding uKIM-1 levels, no relevant statisticalsignificance wasfound between the two groups (p = 0.65). Conclusion:No clinically evident renal dysfunction was observed using the traditional markers of renal function. However, uMCP-1 showed elevated levels in PNH patients, who may have renal damage to the proximal tubule epithelial cells due to inflammatory processes in the intermediate space between the tubules (interstitial nephritis). This result suggests that uMCP-1 could represent a useful biomarker for early detection of renal dysfunction. The lack of significant results with the uKIM-1 biomarker may be attributableto the absenceof renal injury of ischemic origin due to the importantreduction in thrombotic events following
publishDate 2019
dc.date.accessioned.fl_str_mv 2019-11-12T17:17:18Z
dc.date.available.fl_str_mv 2019-11-12T17:17:18Z
dc.date.issued.fl_str_mv 2019-08-29
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
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dc.identifier.citation.fl_str_mv PRO, J. D. Z. Novos biomarcadores de função renal não convencionais em pacientes com hemoglobinúria paroxística noturna. 2018. 68 f. Dissertação (Mestrado em Ciências Médicas) - Faculdade de Medicina, Universidade Federal do Ceará, 2018.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/47684
identifier_str_mv PRO, J. D. Z. Novos biomarcadores de função renal não convencionais em pacientes com hemoglobinúria paroxística noturna. 2018. 68 f. Dissertação (Mestrado em Ciências Médicas) - Faculdade de Medicina, Universidade Federal do Ceará, 2018.
url http://www.repositorio.ufc.br/handle/riufc/47684
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