Biomarcadores inovadores de dano renal em recém-nascidos prematuros com sepse e infecção neonatal

Detalhes bibliográficos
Ano de defesa: 2023
Autor(a) principal: Rebouças, Arthur da Silva
Orientador(a): Lemes, Romélia Pinheiro Gonçalves
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
Área do conhecimento CNPq:
Link de acesso: http://repositorio.ufc.br/handle/riufc/75438
Resumo: Acute Kidney Injury (AKI) is one of the most commonly associated complications with neonatal infections (NI), as well as with sepsis. AKI consists of a sudden reduction in renal function and can be fatal, being considered one of the main causes of morbidity and mortality in premature neonates. Renal impairment in sepsis is due to the mechanism of renal ischemia/reperfusion, which is described as the main cause of AKI. Additionally, reduced renal blood flow and hypoperfusion result in low oxygen demands that induce injury to tubular epithelial cells, apoptosis, and acute tubular necrosis in cases of prolonged hypoperfusion. The diagnosis of AKI is clinically evident by an increase in serum creatinine levels, a criterion that is imprecise and late, as its levels decrease after a loss of 50% of renal function and reflect maternal levels during the first 48 hours of life. The use of innovative biomarkers in the early diagnosis of AKI has been reported in the literature, including urinary cystatin-C (uCysC) and neutrophil gelatinase-associated lipocalin (uNGAL). It is noteworthy that uCysC and uNGAL, in addition to being non- invasive, are not influenced by muscle mass, sex, age, or maternal levels. The present study aimed to evaluate innovative biomarkers of renal damage, uNGAL and uCysC, as predictors in premature neonates diagnosed with sepsis and NI. This was a cross- sectional, descriptive, and observational study with 64 premature neonates, including 20 with NI, 20 with neonatal sepsis (NS), and 20 controls, at the Assis Chateaubriand School Maternity Hospital (MEAC), Fortaleza-Ceará. The diagnosis of NI and sepsis was made using MEAC clinical protocols. The anthropometric, clinical, and laboratory variables of the neonates and the clinical variables of the mothers were obtained from medical records. The analysis of uCysC and uNGAL was performed using an enzyme-linked immunosorbent assay (ELISA) methodology. Statistical significance was set at p<0.05. A total of 47 (73.4%) were male and mostly appropriate for gestational age (AGA). The evaluation of AKI by neonatal KDIGO demonstrated a total of 11 (17.2%), with 4 (20%) with NI and 7 (35%) with sepsis. The mean values of uCysC were 872.29 ng/ml-Cr in the NI group, 3058.93 ng/ml-Cr in the sepsis group, and 152.19 ng/ml-Cr in the control group. The mean values of uNGAL were 42.1 ng/ml-Cr in the NI group, 43.95 ng/ml-Cr in the sepsis group, and 12.5 ng/ml-Cr in the control group. There was a significant difference in uCysC and uNGAL levels between the NI and sepsis groups compared to the control group. uCysC was associated with the following clinical variables: respiratory complications, respiratory distress syndrome, mechanical ventilation, and orotracheal intubation. uNGAL levels were associated with variables such as hospitalization time >30 days, AKI by nKDIGO, mechanical ventilation, intubation, resuscitation in the delivery room, and respiratory distress/SDR. It is concluded that uCysC and uNGAL are promising biomarkers in the early diagnosis of renal damage in premature neonates with NI and sepsis.
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spelling Rebouças, Arthur da SilvaSilva Júnior, Geraldo Bezerra daLemes, Romélia Pinheiro Gonçalves2023-12-21T11:20:28Z2023-12-21T11:20:28Z2023REBOUÇAS, Arthur da Silva. Biomarcadores inovadores de dano renal em recém-nascidos prematuros com sepse e infecção neonatal. 2023. 70 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://www.repositorio.ufc.br/handle/riufc/75438. Acesso em: 21 dez. 2023.http://repositorio.ufc.br/handle/riufc/75438Acute Kidney Injury (AKI) is one of the most commonly associated complications with neonatal infections (NI), as well as with sepsis. AKI consists of a sudden reduction in renal function and can be fatal, being considered one of the main causes of morbidity and mortality in premature neonates. Renal impairment in sepsis is due to the mechanism of renal ischemia/reperfusion, which is described as the main cause of AKI. Additionally, reduced renal blood flow and hypoperfusion result in low oxygen demands that induce injury to tubular epithelial cells, apoptosis, and acute tubular necrosis in cases of prolonged hypoperfusion. The diagnosis of AKI is clinically evident by an increase in serum creatinine levels, a criterion that is imprecise and late, as its levels decrease after a loss of 50% of renal function and reflect maternal levels during the first 48 hours of life. The use of innovative biomarkers in the early diagnosis of AKI has been reported in the literature, including urinary cystatin-C (uCysC) and neutrophil gelatinase-associated lipocalin (uNGAL). It is noteworthy that uCysC and uNGAL, in addition to being non- invasive, are not influenced by muscle mass, sex, age, or maternal levels. The present study aimed to evaluate innovative biomarkers of renal damage, uNGAL and uCysC, as predictors in premature neonates diagnosed with sepsis and NI. This was a cross- sectional, descriptive, and observational study with 64 premature neonates, including 20 with NI, 20 with neonatal sepsis (NS), and 20 controls, at the Assis Chateaubriand School Maternity Hospital (MEAC), Fortaleza-Ceará. The diagnosis of NI and sepsis was made using MEAC clinical protocols. The anthropometric, clinical, and laboratory variables of the neonates and the clinical variables of the mothers were obtained from medical records. The analysis of uCysC and uNGAL was performed using an enzyme-linked immunosorbent assay (ELISA) methodology. Statistical significance was set at p<0.05. A total of 47 (73.4%) were male and mostly appropriate for gestational age (AGA). The evaluation of AKI by neonatal KDIGO demonstrated a total of 11 (17.2%), with 4 (20%) with NI and 7 (35%) with sepsis. The mean values of uCysC were 872.29 ng/ml-Cr in the NI group, 3058.93 ng/ml-Cr in the sepsis group, and 152.19 ng/ml-Cr in the control group. The mean values of uNGAL were 42.1 ng/ml-Cr in the NI group, 43.95 ng/ml-Cr in the sepsis group, and 12.5 ng/ml-Cr in the control group. There was a significant difference in uCysC and uNGAL levels between the NI and sepsis groups compared to the control group. uCysC was associated with the following clinical variables: respiratory complications, respiratory distress syndrome, mechanical ventilation, and orotracheal intubation. uNGAL levels were associated with variables such as hospitalization time >30 days, AKI by nKDIGO, mechanical ventilation, intubation, resuscitation in the delivery room, and respiratory distress/SDR. It is concluded that uCysC and uNGAL are promising biomarkers in the early diagnosis of renal damage in premature neonates with NI and sepsis.A Injúria Renal Aguda (IRA) é uma das complicações mais associadas as infecções neonatais (INN), bem como na Sepse. A mesma consiste em uma redução súbita da função renal, podendo ser fatal, sendo considerada como uma das principais causas de morbimortalidade em neonatos prematuros. O comprometimento renal na sepse se deve ao mecanismo de isquemia/reperfusão renal que é descrito como a principal causa de IRA. Além disso a redução do fluxo sanguíneo renal e hipoperfusão resultam em baixas demandas de oxigênio que induzem a lesão das células do epitélio tubular, apoptose e a necrose tubular aguda em casos de hipoperfusão prolongada. O diagnóstico da IRA é clinicamente evidenciado pelo aumento dos níveis de creatinina sérica, critério este pouco preciso e tardio, visto que seus níveis reduzem após perda de 50% da função renal, além de refletir os níveis maternos durante as primeiras 48 horas de vida. O uso de biomarcadores inovadores no diagnóstico precoce da IRA tem sido reportado na literatura dentre eles a Cistatina-C (uCysC) e o NGAL (uNGAL) urinário. Destaca-se ainda que a uCysC e o uNGAL, além de não serem invasivos, não se deixam influenciar por massa muscular, sexo, idade e níveis maternas. O presente estudo teve como objetivo avaliar os biomarcadores inovadores de dano renal uNGAL e uCysC, preditores em RNs prematuros com diagnóstico de sepse e INN. Trata-se de um estudo transversal, descritivo e observacional com 64 RNs prematuros, sendo 20 prematuros com infecção neonatal (INN), 20 com sepse neonatal (RNsepse) e 20 controles, na Maternidade Escola Assis Chateaubriand (MEAC), Fortaleza - Ceará. O diagnóstico de INN e sepse foi realizado através de protocolos clínicos da MEAC. As variáveis antropométricas, clínicas e laboratoriais dos RNs e as variaveis clínicas das mães foram obtidas de prontuários clínicos. As análises de uCysC e da uNGAL foram realizadas por metodologia de imunoensaio enzimático (ELISA). A significância estatística com p<0,05. Um total de 47 (73,4%) do sexo masculino e na sua maioria apropriados para idade gestacional (AIG). A avaliação da IRA pelo KDIGO neonatal demonstrou um total de 11(17,2%), sendo 4(20%) com INN e 7(35%) com sepse. Os valores médios de uCysC foram 872,29 ng/ml-Cr no grupo com INN, 3058,93 ng/ml-Cr na sepse e 152,19 ng/ml- Cr no grupo controle. Os valores médios de uNGAL foram 42,1 ng/ml-Cr no grupo com INN, 43,95 ng/ml-Cr na sepse e 12,5 ng/ml-Cr no grupo controle. Houve uma diferença significante dos níveis de uCysC e de uNGAL entre os grupos com INN e Sepse em relação ao grupo controle. A uCysC apresentou associação com as seguintes variáveis clinicas: intercorrências respiratórias; síndrome do desconforto respiratório; ventilação mecânica e intubação orotraqueal. Os níveis de uNGAL se associou com as variáveis : tempo de internação hospitalar >30 dias; IRA pelo nKDIGO; ventilação mecânica; intubação; reanimação na sala de parto e com desconforto respiratório/ SDR. Conclui-se que a uCysC e o uNGAL são biomarcadores promissores no diagnóstico precoce de dano renal, em RNs prematuros com INN e com sepse.Biomarcadores inovadores de dano renal em recém-nascidos prematuros com sepse e infecção neonatalinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisInjúria Renal AgudaSepseBiomarcadoresAcute Kidney InjurySepsisBiomarkersCNPQ::CIENCIAS DA SAUDE::FARMACIAinfo:eu-repo/semantics/openAccessporreponame:Repositório Institucional da Universidade Federal do Ceará (UFC)instname:Universidade Federal do Ceará (UFC)instacron:UFChttp://lattes.cnpq.br/9889254293980897https://orcid.org/0000-0003-3178-412Xhttp://lattes.cnpq.br/8202510508068072https://orcid.org/0000-0002-8971-0994http://lattes.cnpq.br/7234328753543020ORIGINAL2023_dis_asrebouças.pdf2023_dis_asrebouças.pdfapplication/pdf1634133http://repositorio.ufc.br/bitstream/riufc/75438/4/2023_dis_asrebou%c3%a7as.pdf3a2f121ba9b2e5356cd096815bfe258bMD54LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://repositorio.ufc.br/bitstream/riufc/75438/6/license.txt8a4605be74aa9ea9d79846c1fba20a33MD56riufc/754382023-12-21 08:21:37.174oai:repositorio.ufc.br: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Repositório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2023-12-21T11:21:37Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Biomarcadores inovadores de dano renal em recém-nascidos prematuros com sepse e infecção neonatal
title Biomarcadores inovadores de dano renal em recém-nascidos prematuros com sepse e infecção neonatal
spellingShingle Biomarcadores inovadores de dano renal em recém-nascidos prematuros com sepse e infecção neonatal
Rebouças, Arthur da Silva
CNPQ::CIENCIAS DA SAUDE::FARMACIA
Injúria Renal Aguda
Sepse
Biomarcadores
Acute Kidney Injury
Sepsis
Biomarkers
title_short Biomarcadores inovadores de dano renal em recém-nascidos prematuros com sepse e infecção neonatal
title_full Biomarcadores inovadores de dano renal em recém-nascidos prematuros com sepse e infecção neonatal
title_fullStr Biomarcadores inovadores de dano renal em recém-nascidos prematuros com sepse e infecção neonatal
title_full_unstemmed Biomarcadores inovadores de dano renal em recém-nascidos prematuros com sepse e infecção neonatal
title_sort Biomarcadores inovadores de dano renal em recém-nascidos prematuros com sepse e infecção neonatal
author Rebouças, Arthur da Silva
author_facet Rebouças, Arthur da Silva
author_role author
dc.contributor.co-advisor.none.fl_str_mv Silva Júnior, Geraldo Bezerra da
dc.contributor.author.fl_str_mv Rebouças, Arthur da Silva
dc.contributor.advisor1.fl_str_mv Lemes, Romélia Pinheiro Gonçalves
contributor_str_mv Lemes, Romélia Pinheiro Gonçalves
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::FARMACIA
topic CNPQ::CIENCIAS DA SAUDE::FARMACIA
Injúria Renal Aguda
Sepse
Biomarcadores
Acute Kidney Injury
Sepsis
Biomarkers
dc.subject.ptbr.pt_BR.fl_str_mv Injúria Renal Aguda
Sepse
Biomarcadores
dc.subject.en.pt_BR.fl_str_mv Acute Kidney Injury
Sepsis
Biomarkers
description Acute Kidney Injury (AKI) is one of the most commonly associated complications with neonatal infections (NI), as well as with sepsis. AKI consists of a sudden reduction in renal function and can be fatal, being considered one of the main causes of morbidity and mortality in premature neonates. Renal impairment in sepsis is due to the mechanism of renal ischemia/reperfusion, which is described as the main cause of AKI. Additionally, reduced renal blood flow and hypoperfusion result in low oxygen demands that induce injury to tubular epithelial cells, apoptosis, and acute tubular necrosis in cases of prolonged hypoperfusion. The diagnosis of AKI is clinically evident by an increase in serum creatinine levels, a criterion that is imprecise and late, as its levels decrease after a loss of 50% of renal function and reflect maternal levels during the first 48 hours of life. The use of innovative biomarkers in the early diagnosis of AKI has been reported in the literature, including urinary cystatin-C (uCysC) and neutrophil gelatinase-associated lipocalin (uNGAL). It is noteworthy that uCysC and uNGAL, in addition to being non- invasive, are not influenced by muscle mass, sex, age, or maternal levels. The present study aimed to evaluate innovative biomarkers of renal damage, uNGAL and uCysC, as predictors in premature neonates diagnosed with sepsis and NI. This was a cross- sectional, descriptive, and observational study with 64 premature neonates, including 20 with NI, 20 with neonatal sepsis (NS), and 20 controls, at the Assis Chateaubriand School Maternity Hospital (MEAC), Fortaleza-Ceará. The diagnosis of NI and sepsis was made using MEAC clinical protocols. The anthropometric, clinical, and laboratory variables of the neonates and the clinical variables of the mothers were obtained from medical records. The analysis of uCysC and uNGAL was performed using an enzyme-linked immunosorbent assay (ELISA) methodology. Statistical significance was set at p<0.05. A total of 47 (73.4%) were male and mostly appropriate for gestational age (AGA). The evaluation of AKI by neonatal KDIGO demonstrated a total of 11 (17.2%), with 4 (20%) with NI and 7 (35%) with sepsis. The mean values of uCysC were 872.29 ng/ml-Cr in the NI group, 3058.93 ng/ml-Cr in the sepsis group, and 152.19 ng/ml-Cr in the control group. The mean values of uNGAL were 42.1 ng/ml-Cr in the NI group, 43.95 ng/ml-Cr in the sepsis group, and 12.5 ng/ml-Cr in the control group. There was a significant difference in uCysC and uNGAL levels between the NI and sepsis groups compared to the control group. uCysC was associated with the following clinical variables: respiratory complications, respiratory distress syndrome, mechanical ventilation, and orotracheal intubation. uNGAL levels were associated with variables such as hospitalization time >30 days, AKI by nKDIGO, mechanical ventilation, intubation, resuscitation in the delivery room, and respiratory distress/SDR. It is concluded that uCysC and uNGAL are promising biomarkers in the early diagnosis of renal damage in premature neonates with NI and sepsis.
publishDate 2023
dc.date.accessioned.fl_str_mv 2023-12-21T11:20:28Z
dc.date.available.fl_str_mv 2023-12-21T11:20:28Z
dc.date.issued.fl_str_mv 2023
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/masterThesis
format masterThesis
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dc.identifier.citation.fl_str_mv REBOUÇAS, Arthur da Silva. Biomarcadores inovadores de dano renal em recém-nascidos prematuros com sepse e infecção neonatal. 2023. 70 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://www.repositorio.ufc.br/handle/riufc/75438. Acesso em: 21 dez. 2023.
dc.identifier.uri.fl_str_mv http://repositorio.ufc.br/handle/riufc/75438
identifier_str_mv REBOUÇAS, Arthur da Silva. Biomarcadores inovadores de dano renal em recém-nascidos prematuros com sepse e infecção neonatal. 2023. 70 f. Dissertação (Mestrado em Ciências Farmacêuticas) - Faculdade de Farmácia, Odontologia e Enfermagem, Universidade Federal do Ceará, Fortaleza, 2023. Disponível em: http://www.repositorio.ufc.br/handle/riufc/75438. Acesso em: 21 dez. 2023.
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