Avaliação de novos biomarcadores no diagnóstico precoce da lesão renal aguda em pacientes com leishmaniose visceral em uso de Anfotericina B lipossomal

Detalhes bibliográficos
Ano de defesa: 2018
Autor(a) principal: Bezerra, Gabriela Freire
Orientador(a): Martins, Alice Maria Costa
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/34433
Resumo: The use of amphotericin B is very effective for treatment of visceral leishmaniasis (VL), but it is one of the main causes of acute kidney injury (AKI) in these patients. The liposomal formulation has less nephrotoxicity, but few studies with renal biomarkers have been done evaluating these effects in patients with VL. Aims: To study the association of the use of liposomal Anf-B with renal injury in patients with visceral leishmaniasis Methods: A prospective and longitudinal study was conducted between April 2015 and January 2018, and after exclusion criteria, 17 patients with VL were hospitalized in a reference hospital of infectious disease, Fortaleza, Ceará. The work was approved by the ethics committee CAAE: 61488016.8.3001.5044. The serum and urine were collected in two periods, first before patients started treatment (time 1) and the second at 72 hours to 168 hours after starting treatment with liposomal Anf-B (time 2). The renal parameters evaluated were: glomerular filtration rate (GFR) estimated by CKD-EPI, creatinine and serum urea, fractional excretion of sodium and potassium, proteinuria, albuminuria. Urinary biomarkers, MCP-1, KIM-1, VEGF and inflamatory biomarkers, IL-6, IFN-y were made by the enzyme-linked immunosorbent assay (ELISA) Results: Patients had a mean age of 43 ± 16 years and 12 (71%) were males. In the paired analysis, it was observed that during the treatment the patients did not have significant increases of creatinine and serum urea, as well as a decrease of the GFR. In addition, there was no difference between the fractional excretion of sodium and potassium and also between proteinuria and albuminuria. Regarding the biomarkers, urinary MCP-1 and KIM-1 showed significant increases during the use of liposomal Anf-B; (656.02 (413.81 - 929.55) vs 1871.92 (834.25 - 2299.33) pg / mg-Cr, p <0.05) and (1.62 (1.20-1.0, 97) vs. 2.51 (1.85-3.24) ng / mg-Cr, p <0.05), respectively. IL-6 levels decreased significantly during treatment (17,37 (8,74 – 49,08) vs 0,21 (0,00 – 3,55) pg/mL, p<0,05). The levels of VEGF and INF-y did not show significant differences. Besides that, urinary MCP-1 levels correlated statistically with the renal markers currently used in clinical practice. Conclusions: The use of liposomal Anf-B did not present significant nephrotoxicity according to the classic parameters of renal function evaluated, but may have contributed to renal injury evidenced by elevation of urinary MCP-1 and urinary KIM-1.
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spelling Bezerra, Gabriela FreireMartins, Alice Maria Costa2018-07-26T12:49:26Z2018-07-26T12:49:26Z2018-07-17BEZERRA, G. F. Avaliação de novos biomarcadores no diagnóstico precoce da lesão renal aguda em pacientes com leishmaniose visceral em uso de Anfotericina B lipossomal. 2018. 80 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2018.http://www.repositorio.ufc.br/handle/riufc/34433The use of amphotericin B is very effective for treatment of visceral leishmaniasis (VL), but it is one of the main causes of acute kidney injury (AKI) in these patients. The liposomal formulation has less nephrotoxicity, but few studies with renal biomarkers have been done evaluating these effects in patients with VL. Aims: To study the association of the use of liposomal Anf-B with renal injury in patients with visceral leishmaniasis Methods: A prospective and longitudinal study was conducted between April 2015 and January 2018, and after exclusion criteria, 17 patients with VL were hospitalized in a reference hospital of infectious disease, Fortaleza, Ceará. The work was approved by the ethics committee CAAE: 61488016.8.3001.5044. The serum and urine were collected in two periods, first before patients started treatment (time 1) and the second at 72 hours to 168 hours after starting treatment with liposomal Anf-B (time 2). The renal parameters evaluated were: glomerular filtration rate (GFR) estimated by CKD-EPI, creatinine and serum urea, fractional excretion of sodium and potassium, proteinuria, albuminuria. Urinary biomarkers, MCP-1, KIM-1, VEGF and inflamatory biomarkers, IL-6, IFN-y were made by the enzyme-linked immunosorbent assay (ELISA) Results: Patients had a mean age of 43 ± 16 years and 12 (71%) were males. In the paired analysis, it was observed that during the treatment the patients did not have significant increases of creatinine and serum urea, as well as a decrease of the GFR. In addition, there was no difference between the fractional excretion of sodium and potassium and also between proteinuria and albuminuria. Regarding the biomarkers, urinary MCP-1 and KIM-1 showed significant increases during the use of liposomal Anf-B; (656.02 (413.81 - 929.55) vs 1871.92 (834.25 - 2299.33) pg / mg-Cr, p <0.05) and (1.62 (1.20-1.0, 97) vs. 2.51 (1.85-3.24) ng / mg-Cr, p <0.05), respectively. IL-6 levels decreased significantly during treatment (17,37 (8,74 – 49,08) vs 0,21 (0,00 – 3,55) pg/mL, p<0,05). The levels of VEGF and INF-y did not show significant differences. Besides that, urinary MCP-1 levels correlated statistically with the renal markers currently used in clinical practice. Conclusions: The use of liposomal Anf-B did not present significant nephrotoxicity according to the classic parameters of renal function evaluated, but may have contributed to renal injury evidenced by elevation of urinary MCP-1 and urinary KIM-1.O uso de anfotericina B (Anf-B) é bastante eficaz para o tratamento de leishmaniose visceral (LV), mas é uma das principais causas de lesão renal aguda (LRA) nesses pacientes. A formulação lipossomal tem menor nefrotoxicidade, mas poucos estudos com biomarcadores renais foram feitos avaliando esses efeitos em pacientes com LV. Objetivo: Estudar a associação do uso da Anf-B lipossomal com a injúria renal em pacientes com leishmaniose visceral. Métodos. Foi realizado um estudo prospectivo, longitudinal entre abril de 2015 e janeiro de 2018; após a aplicação de critérios de inclusão e exclusão, foram acompanhados 17 pacientes com LV hospitalizados no Hospital São José de Doenças Infecciosas, Fortaleza, Ceará. O trabalho foi aprovado pelo comitê de ética CAAE: 61488016.8.3001.5044. Foram feitas duas coletas de soro e urina; a primeira na admissão hospitalar antes dos pacientes iniciarem o tratamento (tempo 1) e a segunda entre o período de 72 horas a 168 horas a partir do inicio do tratamento com Anf-B lipossomal (tempo 2). Os parâmetros renais avaliados foram taxa de filtração glomerular (TFG) estimada pelo CKD-EPI, creatinina e uréia sérica, fração de excreção de sódio e potássio, proteinúria, albuminúria e os biomarcadores MCP-1, KIM-1,VEGF urinários, além de IL-6 e IFN-y séricos pelo ensaio imunoenzimático (ELISA). Resultados. Os pacientes tiveram idade média de 43±16 anos e 12 (71%) eram do sexo masculino. Na análise pareada, foi observado que durante o tratamento os pacientes não tiveram aumentos significativos da creatinina e uréia sérica, bem como diminuição da TFG. Além disso, não houve diferença entre a fração de excreção de sódio e potássio e também entre a proteinúria e albuminúria. Em relação aos biomarcadores, o MCP-1 e KIM-1 urinários apresentaram aumentos significativos durante o uso de Anf-B lipossomal; (656,02 (413,81 – 929,55) vs 1871,92 (834,25 – 2299,33) pg/mg-Cr, p<0,05) e (1,62 (1,20 – 1,97) vs 2,51 (1,85 – 3,24) ng/mg-Cr, p<0,05), respectivamente. As concentrações plasmáticas de IL-6 diminuiram de forma significativa durante o tratamento (17,37 (8,74 – 49,08) vs 0,21 (0,00 – 3,55) pg/mL, p<0,05). Os níveis de VEGF e INF-y não apresentaram diferenças significativas. Além disso, os níveis de MCP-1 urinários se correlacionaram estatisticamente com os marcadores renais utilizados atualmente na prática clínica. Conclusões. O uso de Anf-B lipossomal não apresentou nefrotoxicidade importante de acordo com parâmetros clássicos de função renal avaliados, mas pode ter contribuído para algum grau de lesão renal evidenciada pela elevação de MCP-1 urinário e KIM-1 urinário.Anfotericina BBiomarcadoresLesão Renal AgudaLeishmaniose VisceralAvaliação de novos biomarcadores no diagnóstico precoce da lesão renal aguda em pacientes com leishmaniose visceral em uso de Anfotericina B lipossomalNovel biomarkers in early diagnosis of acute renal injury in patients with visceral leishmaniasis in treatment with liposomal Amphotericin Binfo: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/openAccessLICENSElicense.txtlicense.txttext/plain; charset=utf-81812http://repositorio.ufc.br/bitstream/riufc/34433/2/license.txt9351db63ea91b32e01910aaf21c0fd0aMD52ORIGINAL2018_dis_gfbezerra.pdf2018_dis_gfbezerra.pdfapplication/pdf1591468http://repositorio.ufc.br/bitstream/riufc/34433/3/2018_dis_gfbezerra.pdf7675acacb5b9151c2d823349ef6e95e0MD53riufc/344332019-10-16 09:26:55.044oai:repositorio.ufc.br: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ório InstitucionalPUBhttp://www.repositorio.ufc.br/ri-oai/requestbu@ufc.br || repositorio@ufc.bropendoar:2019-10-16T12:26:55Repositório Institucional da Universidade Federal do Ceará (UFC) - Universidade Federal do Ceará (UFC)false
dc.title.pt_BR.fl_str_mv Avaliação de novos biomarcadores no diagnóstico precoce da lesão renal aguda em pacientes com leishmaniose visceral em uso de Anfotericina B lipossomal
dc.title.en.pt_BR.fl_str_mv Novel biomarkers in early diagnosis of acute renal injury in patients with visceral leishmaniasis in treatment with liposomal Amphotericin B
title Avaliação de novos biomarcadores no diagnóstico precoce da lesão renal aguda em pacientes com leishmaniose visceral em uso de Anfotericina B lipossomal
spellingShingle Avaliação de novos biomarcadores no diagnóstico precoce da lesão renal aguda em pacientes com leishmaniose visceral em uso de Anfotericina B lipossomal
Bezerra, Gabriela Freire
Anfotericina B
Biomarcadores
Lesão Renal Aguda
Leishmaniose Visceral
title_short Avaliação de novos biomarcadores no diagnóstico precoce da lesão renal aguda em pacientes com leishmaniose visceral em uso de Anfotericina B lipossomal
title_full Avaliação de novos biomarcadores no diagnóstico precoce da lesão renal aguda em pacientes com leishmaniose visceral em uso de Anfotericina B lipossomal
title_fullStr Avaliação de novos biomarcadores no diagnóstico precoce da lesão renal aguda em pacientes com leishmaniose visceral em uso de Anfotericina B lipossomal
title_full_unstemmed Avaliação de novos biomarcadores no diagnóstico precoce da lesão renal aguda em pacientes com leishmaniose visceral em uso de Anfotericina B lipossomal
title_sort Avaliação de novos biomarcadores no diagnóstico precoce da lesão renal aguda em pacientes com leishmaniose visceral em uso de Anfotericina B lipossomal
author Bezerra, Gabriela Freire
author_facet Bezerra, Gabriela Freire
author_role author
dc.contributor.author.fl_str_mv Bezerra, Gabriela Freire
dc.contributor.advisor1.fl_str_mv Martins, Alice Maria Costa
contributor_str_mv Martins, Alice Maria Costa
dc.subject.por.fl_str_mv Anfotericina B
Biomarcadores
Lesão Renal Aguda
Leishmaniose Visceral
topic Anfotericina B
Biomarcadores
Lesão Renal Aguda
Leishmaniose Visceral
description The use of amphotericin B is very effective for treatment of visceral leishmaniasis (VL), but it is one of the main causes of acute kidney injury (AKI) in these patients. The liposomal formulation has less nephrotoxicity, but few studies with renal biomarkers have been done evaluating these effects in patients with VL. Aims: To study the association of the use of liposomal Anf-B with renal injury in patients with visceral leishmaniasis Methods: A prospective and longitudinal study was conducted between April 2015 and January 2018, and after exclusion criteria, 17 patients with VL were hospitalized in a reference hospital of infectious disease, Fortaleza, Ceará. The work was approved by the ethics committee CAAE: 61488016.8.3001.5044. The serum and urine were collected in two periods, first before patients started treatment (time 1) and the second at 72 hours to 168 hours after starting treatment with liposomal Anf-B (time 2). The renal parameters evaluated were: glomerular filtration rate (GFR) estimated by CKD-EPI, creatinine and serum urea, fractional excretion of sodium and potassium, proteinuria, albuminuria. Urinary biomarkers, MCP-1, KIM-1, VEGF and inflamatory biomarkers, IL-6, IFN-y were made by the enzyme-linked immunosorbent assay (ELISA) Results: Patients had a mean age of 43 ± 16 years and 12 (71%) were males. In the paired analysis, it was observed that during the treatment the patients did not have significant increases of creatinine and serum urea, as well as a decrease of the GFR. In addition, there was no difference between the fractional excretion of sodium and potassium and also between proteinuria and albuminuria. Regarding the biomarkers, urinary MCP-1 and KIM-1 showed significant increases during the use of liposomal Anf-B; (656.02 (413.81 - 929.55) vs 1871.92 (834.25 - 2299.33) pg / mg-Cr, p <0.05) and (1.62 (1.20-1.0, 97) vs. 2.51 (1.85-3.24) ng / mg-Cr, p <0.05), respectively. IL-6 levels decreased significantly during treatment (17,37 (8,74 – 49,08) vs 0,21 (0,00 – 3,55) pg/mL, p<0,05). The levels of VEGF and INF-y did not show significant differences. Besides that, urinary MCP-1 levels correlated statistically with the renal markers currently used in clinical practice. Conclusions: The use of liposomal Anf-B did not present significant nephrotoxicity according to the classic parameters of renal function evaluated, but may have contributed to renal injury evidenced by elevation of urinary MCP-1 and urinary KIM-1.
publishDate 2018
dc.date.accessioned.fl_str_mv 2018-07-26T12:49:26Z
dc.date.available.fl_str_mv 2018-07-26T12:49:26Z
dc.date.issued.fl_str_mv 2018-07-17
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dc.identifier.citation.fl_str_mv BEZERRA, G. F. Avaliação de novos biomarcadores no diagnóstico precoce da lesão renal aguda em pacientes com leishmaniose visceral em uso de Anfotericina B lipossomal. 2018. 80 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2018.
dc.identifier.uri.fl_str_mv http://www.repositorio.ufc.br/handle/riufc/34433
identifier_str_mv BEZERRA, G. F. Avaliação de novos biomarcadores no diagnóstico precoce da lesão renal aguda em pacientes com leishmaniose visceral em uso de Anfotericina B lipossomal. 2018. 80 f. Dissertação (Mestrado em Farmacologia) - Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, 2018.
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