Biomarcadores de injúria tubular aguda como preditores da mortalidade na COVID – 19

Detalhes bibliográficos
Ano de defesa: 2023
Autor(a) principal: Moreira, Gabriela Freire Bezerra
Orientador(a): Martins, Alice Maria Costa
Banca de defesa: Não Informado pela instituição
Tipo de documento: Tese
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
Link de acesso: http://repositorio.ufc.br/handle/riufc/75017
Resumo: COVID-19 is an infectious disease caused by a new type of coronavirus called SARS-CoV-2, which has a high capacity to infect humans and high transmissibility. Acute kidney injury (AKI) is a common complication in severe patients with COVID-19, affecting about 50% of patients in intensive care units (ICU), in addition, kidney injury is a risk factor for mortality. The use of more sensitive and specific urinary biomarkers can be useful in the early detection of kidney injury and can be used as predictors for different events. This work was carried out with the objective of evaluating the role of urinary biomarkers in predicting the mortality of critically ill patients with COVID-19 in the ICU. A prospective study was carried out with participants affected by COVID-19, admitted to the ICU of the Instituto Doutor José Frota (IJF) in Fortaleza, from June 2020 to April 2021 (1st and 2nd wave of COVID-19). Blood and urine samples were collected within 24 hours of admission to the ICU and the participants' medical records were monitored to verify changes in laboratory parameters. AKI was defined according to the KDIGO criteria. The urinary biomarkers MCP-1, Nephrin, NGAL and KIM-1 were quantified by ELISA and the predictive values for mortality of each biomarker were analyzed using ROC curves. Additionally, analyses were performed to estimate the chance of survival at 2 months using regression models. The average age of participants was 57 ± 16 years. Around 69% of participants developed AKI during their hospital stay and 38% died. Nephrin and MCP-1 biomarkers did not show significant differences between survivors and death groups. The biomarkers proteinuria (0.728; p = 0.004), NGAL (0.750; p = 0.002) and KIM-1 (0.749; p = 0.002) showed good values of ROC curves to predict death and in the combined analysis proteinuria*KIM- 1*NGAL was found to provide the best result (0.810; p < 0.001). In Cox regression models, proteinuria/creatinine ratio (>0.90), urinary KIM-1 (>1.8 ng/mg-Cr) and urinary NGAL (>118.8 ng/mg-Cr) were associated with a lower chance of survival at 2 months in the univariate analysis; however, in the multivariate model, after adjustments, only urinary NGAL remained associated, presenting a hazard ratio = 5.666 (95% CI: 1.761–18.227). Tubular renal damage was observed according to changes in the levels of biomarkers of acute tubular injury. KIM-1, NGAL and proteinuria correlated with death, and NGAL was an independent predictor for this outcome.
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spelling Moreira, Gabriela Freire BezerraMartins, Alice Maria Costa2023-11-21T16:45:46Z2023-11-21T16:45:46Z2023MOREIRA, Gabriela Freire Bezerra. Biomarcadores de injúria tubular aguda como preditores da mortalidade na COVID – 19. 2023. 89 f. Tese (Doutorado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://repositorio.ufc.br/handle/riufc/75017. Acesso em: 21 nov. 2023.http://repositorio.ufc.br/handle/riufc/75017COVID-19 is an infectious disease caused by a new type of coronavirus called SARS-CoV-2, which has a high capacity to infect humans and high transmissibility. Acute kidney injury (AKI) is a common complication in severe patients with COVID-19, affecting about 50% of patients in intensive care units (ICU), in addition, kidney injury is a risk factor for mortality. The use of more sensitive and specific urinary biomarkers can be useful in the early detection of kidney injury and can be used as predictors for different events. This work was carried out with the objective of evaluating the role of urinary biomarkers in predicting the mortality of critically ill patients with COVID-19 in the ICU. A prospective study was carried out with participants affected by COVID-19, admitted to the ICU of the Instituto Doutor José Frota (IJF) in Fortaleza, from June 2020 to April 2021 (1st and 2nd wave of COVID-19). Blood and urine samples were collected within 24 hours of admission to the ICU and the participants' medical records were monitored to verify changes in laboratory parameters. AKI was defined according to the KDIGO criteria. The urinary biomarkers MCP-1, Nephrin, NGAL and KIM-1 were quantified by ELISA and the predictive values for mortality of each biomarker were analyzed using ROC curves. Additionally, analyses were performed to estimate the chance of survival at 2 months using regression models. The average age of participants was 57 ± 16 years. Around 69% of participants developed AKI during their hospital stay and 38% died. Nephrin and MCP-1 biomarkers did not show significant differences between survivors and death groups. The biomarkers proteinuria (0.728; p = 0.004), NGAL (0.750; p = 0.002) and KIM-1 (0.749; p = 0.002) showed good values of ROC curves to predict death and in the combined analysis proteinuria*KIM- 1*NGAL was found to provide the best result (0.810; p < 0.001). In Cox regression models, proteinuria/creatinine ratio (>0.90), urinary KIM-1 (>1.8 ng/mg-Cr) and urinary NGAL (>118.8 ng/mg-Cr) were associated with a lower chance of survival at 2 months in the univariate analysis; however, in the multivariate model, after adjustments, only urinary NGAL remained associated, presenting a hazard ratio = 5.666 (95% CI: 1.761–18.227). Tubular renal damage was observed according to changes in the levels of biomarkers of acute tubular injury. KIM-1, NGAL and proteinuria correlated with death, and NGAL was an independent predictor for this outcome.A COVID – 19 é uma doença infecciosa causada por um novo tipo de coronavírus denominado SARS-CoV-2, que possui alta capacidade de infectar seres humanos e alta transmissibilidade. A injúria renal aguda (IRA) é uma complicação comum em pacientes graves com COVID-19, acometendo cerca de 50% dos pacientes nas unidades de terapia intensiva (UTI), além disso, a injúria renal é um fator de risco para a mortalidade. O uso de biomarcadores urinários mais sensíveis e específicos pode ser útil na detecção precoce da injúria renal, e podem ser utilizados como preditores para diferentes eventos. Esse trabalho foi realizado com o objetivo de avaliar o papel dos biomarcadores urinários na predição da mortalidade em pacientes graves com COVID-19. Foi realizado um estudo prospectivo com participantes acometidos pela COVID-19, internados na UTI do Instituto Doutor José Frota (IJF) em Fortaleza, de junho de 2020 a abril de 2021(1ª e 2ª onda da COVID-19). Amostras de sangue e urina foram coletadas em até 24 horas da admissão na UTI e os prontuários dos participantes foram acompanhados a fim de verificar alterações de parâmetros laboratoriais. A definição de IRA foi realizada de acordo com o critério KDIGO. Os biomarcadores urinários MCP-1, Nefrina, NGAL e KIM-1 foram quantificados por ELISA e através de curvas ROC foram analisados os valores preditivos para a mortalidade de cada biomarcador. Além disso, foram feitas análises para estimar a chance de sobrevivência em 2 meses por meio de modelos de regressão. A idade média dos participantes foi de 57 ± 16 anos. Cerca de 69% dos participantes desenvolveram IRA durante a internação hospitalar e 38% foi a óbito. Os biomarcadores urinários nefrina e MCP-1 não apresentaram diferenças significativas entre os grupos sobreviventes e óbito. Já os biomarcadores proteinúria (0,728; p = 0,004), NGAL (0,750; p = 0,002) e KIM-1(0,749; p = 0,002) apresentaram bons valores de curvas ROC para prever o óbito. Na análise combinada proteinúria*KIM-1*NGAL foi encontrado o melhor resultado (0,810; p < 0,001). Nos modelos de regressão de cox, na análise univariada, a razão proteinúria/creatinina (>0,90), KIM-1 urinário (>1,8 ng/mg-Cr) e NGAL urinária (>118,8 ng/mg-Cr) se associaram a uma menor chance de sobrevida em 2 meses; porém no modelo multivariado, após os ajustes apenas a NGAL urinária se manteve associada, apresentando hazard ratio = 5,666 (IC 95%: 1,761–18,227). Foi observado um dano renal tubular de acordo com as alterações nos níveis dos biomarcadores de injúria tubular aguda. KIM-1, NGAL e proteinúria se correlacionaram com o óbito, e a NGAL foi preditora independente para este desfecho.Biomarcadores de injúria tubular aguda como preditores da mortalidade na COVID – 19Biomarkers of acute tubular injury as predictors of mortality in covid-19info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisCOVID-19Injúria Renal AgudaBiomarcadoresLipocalina-2COVID-19Acute Kidney InjuryBiomarkersLipocalin-2info:eu-repo/semantics/openAccessporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFChttp://lattes.cnpq.br/2259347180366778http://lattes.cnpq.br/7532334620264577ORIGINAL2023_tese_gfbmoreira.pdf2023_tese_gfbmoreira.pdfapplication/pdf5785271http://repositorio.ufc.br/bitstream/riufc/75017/1/2023_tese_gfbmoreira.pdf1cee6bff0a107a9c89f9cd8df31fdff3MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/75017/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52riufc/750172023-11-21 14:12:23.141oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2023-11-21T17:12:23Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Biomarcadores de injúria tubular aguda como preditores da mortalidade na COVID – 19
dc.title.en.pt_BR.fl_str_mv Biomarkers of acute tubular injury as predictors of mortality in covid-19
title Biomarcadores de injúria tubular aguda como preditores da mortalidade na COVID – 19
spellingShingle Biomarcadores de injúria tubular aguda como preditores da mortalidade na COVID – 19
Moreira, Gabriela Freire Bezerra
COVID-19
Injúria Renal Aguda
Biomarcadores
Lipocalina-2
COVID-19
Acute Kidney Injury
Biomarkers
Lipocalin-2
title_short Biomarcadores de injúria tubular aguda como preditores da mortalidade na COVID – 19
title_full Biomarcadores de injúria tubular aguda como preditores da mortalidade na COVID – 19
title_fullStr Biomarcadores de injúria tubular aguda como preditores da mortalidade na COVID – 19
title_full_unstemmed Biomarcadores de injúria tubular aguda como preditores da mortalidade na COVID – 19
title_sort Biomarcadores de injúria tubular aguda como preditores da mortalidade na COVID – 19
author Moreira, Gabriela Freire Bezerra
author_facet Moreira, Gabriela Freire Bezerra
author_role author
dc.contributor.author.fl_str_mv Moreira, Gabriela Freire Bezerra
dc.contributor.advisor1.fl_str_mv Martins, Alice Maria Costa
contributor_str_mv Martins, Alice Maria Costa
dc.subject.ptbr.pt_BR.fl_str_mv COVID-19
Injúria Renal Aguda
Biomarcadores
Lipocalina-2
topic COVID-19
Injúria Renal Aguda
Biomarcadores
Lipocalina-2
COVID-19
Acute Kidney Injury
Biomarkers
Lipocalin-2
dc.subject.en.pt_BR.fl_str_mv COVID-19
Acute Kidney Injury
Biomarkers
Lipocalin-2
description COVID-19 is an infectious disease caused by a new type of coronavirus called SARS-CoV-2, which has a high capacity to infect humans and high transmissibility. Acute kidney injury (AKI) is a common complication in severe patients with COVID-19, affecting about 50% of patients in intensive care units (ICU), in addition, kidney injury is a risk factor for mortality. The use of more sensitive and specific urinary biomarkers can be useful in the early detection of kidney injury and can be used as predictors for different events. This work was carried out with the objective of evaluating the role of urinary biomarkers in predicting the mortality of critically ill patients with COVID-19 in the ICU. A prospective study was carried out with participants affected by COVID-19, admitted to the ICU of the Instituto Doutor José Frota (IJF) in Fortaleza, from June 2020 to April 2021 (1st and 2nd wave of COVID-19). Blood and urine samples were collected within 24 hours of admission to the ICU and the participants' medical records were monitored to verify changes in laboratory parameters. AKI was defined according to the KDIGO criteria. The urinary biomarkers MCP-1, Nephrin, NGAL and KIM-1 were quantified by ELISA and the predictive values for mortality of each biomarker were analyzed using ROC curves. Additionally, analyses were performed to estimate the chance of survival at 2 months using regression models. The average age of participants was 57 ± 16 years. Around 69% of participants developed AKI during their hospital stay and 38% died. Nephrin and MCP-1 biomarkers did not show significant differences between survivors and death groups. The biomarkers proteinuria (0.728; p = 0.004), NGAL (0.750; p = 0.002) and KIM-1 (0.749; p = 0.002) showed good values of ROC curves to predict death and in the combined analysis proteinuria*KIM- 1*NGAL was found to provide the best result (0.810; p < 0.001). In Cox regression models, proteinuria/creatinine ratio (>0.90), urinary KIM-1 (>1.8 ng/mg-Cr) and urinary NGAL (>118.8 ng/mg-Cr) were associated with a lower chance of survival at 2 months in the univariate analysis; however, in the multivariate model, after adjustments, only urinary NGAL remained associated, presenting a hazard ratio = 5.666 (95% CI: 1.761–18.227). Tubular renal damage was observed according to changes in the levels of biomarkers of acute tubular injury. KIM-1, NGAL and proteinuria correlated with death, and NGAL was an independent predictor for this outcome.
publishDate 2023
dc.date.accessioned.fl_str_mv 2023-11-21T16:45:46Z
dc.date.available.fl_str_mv 2023-11-21T16:45:46Z
dc.date.issued.fl_str_mv 2023
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dc.identifier.citation.fl_str_mv MOREIRA, Gabriela Freire Bezerra. Biomarcadores de injúria tubular aguda como preditores da mortalidade na COVID – 19. 2023. 89 f. Tese (Doutorado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://repositorio.ufc.br/handle/riufc/75017. Acesso em: 21 nov. 2023.
dc.identifier.uri.fl_str_mv http://repositorio.ufc.br/handle/riufc/75017
identifier_str_mv MOREIRA, Gabriela Freire Bezerra. Biomarcadores de injúria tubular aguda como preditores da mortalidade na COVID – 19. 2023. 89 f. Tese (Doutorado em Farmacologia) – Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://repositorio.ufc.br/handle/riufc/75017. Acesso em: 21 nov. 2023.
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