Ácido úrico e sua associação com o dano tubular e inflamação renal em pacientes com diabetes mellitus tipo 2
Ano de defesa: | 2017 |
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Autor(a) principal: | |
Orientador(a): | |
Banca de defesa: | |
Tipo de documento: | Dissertação |
Tipo de acesso: | Acesso aberto |
Idioma: | por |
Instituição de defesa: |
Universidade Federal de Santa Maria
Brasil Farmácia UFSM Programa de Pós-Graduação em Ciências Farmacêuticas Centro de Ciências da Saúde |
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://repositorio.ufsm.br/handle/1/18183 |
Resumo: | Hyperuricemia has emerged as a risk factor for the development of diabetes mellitus (DM) and consequently associated with the onset of diabetes kidney disease (DKD). It is known that the development of DKD is a complex process that promotes changes in different portions of the kidneys, and although hyperglycemia is a key mechanism in this process, it is not the only one. The inflammation has been evidenced as an important contributor to the pathophysiology of DKD. It is known that uric acid is a molecule that favors inflammation, both at the systemic and renal levels, contributing to kidney damage. In addition, uric acid has the potential to promote processes of afferent arteriolopathy, glomerular hypertrophy as well as direct damage to renal tubular cells. Damage to the renal tubules seems to be a primary contributor to the development of DKD and can be identified early by the presence of tubular damage markers. Despite the actions described, the mechanism by which uric acid acts in the context of DKD is not yet fully understood. Thus, the objective of this study was to evaluate the association between elevated uric acid levels and renal tubular damage, as well as its relation with renal inflammation in patients with type 2 diabetes mellitus (type 2 DM). A total of 125 patients with type 2 DM from the University Hospital of Santa Maria (HUSM), who had serum uric acid levels and other biochemical parameters measured, were recruited. In addition, urinary levels of the renal damage molecule-1 (KIM-1), used as a biomarker of tubular damage, and urinary levels of inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 ( IL- 6) and tumor necrosis factor alpha (TNF-alpha), used to check the renal inflammatory process. Patients were stratified into two groups according to the following levels of uric acid: <6.0 mg / dL and ≥6.0 mg / dL, and were compared for urinary levels of KIM-1, IL-1, IL -6 and TNF-alpha. Patients with higher serum uric acid levels were those who demonstrated higher urinary levels of KIM-1 and renal inflammation, as measured by quantification of urinary cytokines. It was also found that renal inflammation was positively correlated with the tubular damage process, as positive correlations were observed between the levels of KIM-1 and the proinflammatory cytokines evaluated in this study (IL-1, IL-6 and TNF-alpha ). Thus, we suggest that elevation of serum uric acid levels may be associated with a greater degree of tubular damage and renal inflammation in patients with type 2 DM. In addition, we believe that inflammation plays a significant role in the development of tubular renal damage and that uric acid may be promoting this inflammatory context. |
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Ácido úrico e sua associação com o dano tubular e inflamação renal em pacientes com diabetes mellitus tipo 2Uric acid and its association with tubular damage and renal inflammation in patients with type 2 diabetes mellitusHiperuricemiaDiabetes tipo 2Doença renal do diabetesDano tubularKIM-1InflamaçãoCitocinasHyperuricemiaType 2 diabetesKidney disease of diabetesTubular damageInflammationCytokinesCNPQ::CIENCIAS DA SAUDE::FARMACIAHyperuricemia has emerged as a risk factor for the development of diabetes mellitus (DM) and consequently associated with the onset of diabetes kidney disease (DKD). It is known that the development of DKD is a complex process that promotes changes in different portions of the kidneys, and although hyperglycemia is a key mechanism in this process, it is not the only one. The inflammation has been evidenced as an important contributor to the pathophysiology of DKD. It is known that uric acid is a molecule that favors inflammation, both at the systemic and renal levels, contributing to kidney damage. In addition, uric acid has the potential to promote processes of afferent arteriolopathy, glomerular hypertrophy as well as direct damage to renal tubular cells. Damage to the renal tubules seems to be a primary contributor to the development of DKD and can be identified early by the presence of tubular damage markers. Despite the actions described, the mechanism by which uric acid acts in the context of DKD is not yet fully understood. Thus, the objective of this study was to evaluate the association between elevated uric acid levels and renal tubular damage, as well as its relation with renal inflammation in patients with type 2 diabetes mellitus (type 2 DM). A total of 125 patients with type 2 DM from the University Hospital of Santa Maria (HUSM), who had serum uric acid levels and other biochemical parameters measured, were recruited. In addition, urinary levels of the renal damage molecule-1 (KIM-1), used as a biomarker of tubular damage, and urinary levels of inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 ( IL- 6) and tumor necrosis factor alpha (TNF-alpha), used to check the renal inflammatory process. Patients were stratified into two groups according to the following levels of uric acid: <6.0 mg / dL and ≥6.0 mg / dL, and were compared for urinary levels of KIM-1, IL-1, IL -6 and TNF-alpha. Patients with higher serum uric acid levels were those who demonstrated higher urinary levels of KIM-1 and renal inflammation, as measured by quantification of urinary cytokines. It was also found that renal inflammation was positively correlated with the tubular damage process, as positive correlations were observed between the levels of KIM-1 and the proinflammatory cytokines evaluated in this study (IL-1, IL-6 and TNF-alpha ). Thus, we suggest that elevation of serum uric acid levels may be associated with a greater degree of tubular damage and renal inflammation in patients with type 2 DM. In addition, we believe that inflammation plays a significant role in the development of tubular renal damage and that uric acid may be promoting this inflammatory context.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESA hiperuricemia tem emergido como fator de risco para o desenvolvimento de diabetes mellitus (DM) e, consequentemente associada ao surgimento da doença renal do diabetes (DRD). Sabe-se que o desenvolvimento da DRD é um processo complexo que promove alterações em diferentes porções dos rins e, embora a hiperglicemia seja um mecanismo chave nesse processo, ela não é o único. A inflamação tem sido evidenciada como uma importante contribuinte para a fisiopatologia da DRD. Sabe-se que o ácido úrico é uma molécula que favorece a inflamação, tanto a nível sistêmico quanto renal, contribuindo para o dano renal. Além disso, o ácido úrico possui potencial para promover processos de arteriolopatia aferente, hipertrofia glomerular, bem como o dano direto às células tubulares renais. O dano aos túbulos renais parece ser um contribuinte primário para o desenvolvimento da DRD e pode ser identificado precocemente pela presença de marcadores de dano tubular. Apesar das ações descritas, ainda não se conhece completamente o mecanismo pelo qual o ácido úrico atua no contexto da DRD. Dessa forma, o objetivo deste trabalho foi avaliar a existência da associação entre os elevados níveis séricos de ácido úrico e o dano tubular renal, bem como sua relação com a inflamação renal em pacientes com diabetes mellitus tipo 2 (DM tipo 2). Foram recrutados 125 pacientes com DM tipo 2 provenientes do Hospital Universitário de Santa Maria (HUSM), que tiveram os níveis séricos de ácido úrico e de outros parâmetros bioquímicos mensurados. Além disso, foram quantificados os níveis urinários da molécula de dano renal-1 (KIM-1), utilizada como biomarcador de dano tubular, e os níveis urinários de citocinas inflamatórias como a interleucina-1 (IL-1), interleucina-6 (IL-6) e fator de necrose tumoral alfa (TNF-alfa), utilizadas para a verificação do processo inflamatório renal. Os pacientes foram estratificados em dois grupos de acordo com os seguintes níveis de ácido úrico: <6,0 mg/dL e ≥6,0 mg/dL, e foram comparados quanto aos níveis urinários de KIM-1, IL-1, IL-6 e TNFalfa. Os pacientes com níveis séricos mais elevados de ácido úrico foram aqueles que demonstraram maiores níveis urinários de KIM-1 e de inflamação renal, avaliada pela quantificação das citocinas urinárias. Também foi verificado que a inflamação renal foi positivamente correlacionada com o processo de dano tubular, visto que foram observadas correlações positivas entre os níveis de KIM-1 e as citocinas próinflamatórias avaliadas neste estudo (IL-1, IL-6 eTNF-alfa). Desta forma, sugerimos que a elevação dos níveis séricos de ácido úrico possa estar associada a um maior grau de dano tubular e inflamação renal em pacientes com DM tipo 2. Além disso, acreditamos que a inflamação participe consideravelmente do desenvolvimento do dano renal tubular e que o ácido úrico possa estar promovendo esse contexto inflamatório.Universidade Federal de Santa MariaBrasilFarmáciaUFSMPrograma de Pós-Graduação em Ciências FarmacêuticasCentro de Ciências da SaúdeMoresco, Rafael Noalhttp://lattes.cnpq.br/2269922709577261Vaucher, Rodrigo de Almeidahttp://lattes.cnpq.br/0953074420467371Brucker, Natáliahttp://lattes.cnpq.br/7188237428821146Guarda, Naiara dos Santos2019-09-10T19:24:41Z2019-09-10T19:24:41Z2017-12-15info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesisapplication/pdfhttp://repositorio.ufsm.br/handle/1/18183porAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessreponame:Manancial - Repositório Digital da UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSM2022-10-07T19:04:14Zoai:repositorio.ufsm.br:1/18183Biblioteca Digital de Teses e Dissertaçõeshttps://repositorio.ufsm.br/ONGhttps://repositorio.ufsm.br/oai/requestatendimento.sib@ufsm.br||tedebc@gmail.comopendoar:2022-10-07T19:04:14Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM)false |
dc.title.none.fl_str_mv |
Ácido úrico e sua associação com o dano tubular e inflamação renal em pacientes com diabetes mellitus tipo 2 Uric acid and its association with tubular damage and renal inflammation in patients with type 2 diabetes mellitus |
title |
Ácido úrico e sua associação com o dano tubular e inflamação renal em pacientes com diabetes mellitus tipo 2 |
spellingShingle |
Ácido úrico e sua associação com o dano tubular e inflamação renal em pacientes com diabetes mellitus tipo 2 Guarda, Naiara dos Santos Hiperuricemia Diabetes tipo 2 Doença renal do diabetes Dano tubular KIM-1 Inflamação Citocinas Hyperuricemia Type 2 diabetes Kidney disease of diabetes Tubular damage Inflammation Cytokines CNPQ::CIENCIAS DA SAUDE::FARMACIA |
title_short |
Ácido úrico e sua associação com o dano tubular e inflamação renal em pacientes com diabetes mellitus tipo 2 |
title_full |
Ácido úrico e sua associação com o dano tubular e inflamação renal em pacientes com diabetes mellitus tipo 2 |
title_fullStr |
Ácido úrico e sua associação com o dano tubular e inflamação renal em pacientes com diabetes mellitus tipo 2 |
title_full_unstemmed |
Ácido úrico e sua associação com o dano tubular e inflamação renal em pacientes com diabetes mellitus tipo 2 |
title_sort |
Ácido úrico e sua associação com o dano tubular e inflamação renal em pacientes com diabetes mellitus tipo 2 |
author |
Guarda, Naiara dos Santos |
author_facet |
Guarda, Naiara dos Santos |
author_role |
author |
dc.contributor.none.fl_str_mv |
Moresco, Rafael Noal http://lattes.cnpq.br/2269922709577261 Vaucher, Rodrigo de Almeida http://lattes.cnpq.br/0953074420467371 Brucker, Natália http://lattes.cnpq.br/7188237428821146 |
dc.contributor.author.fl_str_mv |
Guarda, Naiara dos Santos |
dc.subject.por.fl_str_mv |
Hiperuricemia Diabetes tipo 2 Doença renal do diabetes Dano tubular KIM-1 Inflamação Citocinas Hyperuricemia Type 2 diabetes Kidney disease of diabetes Tubular damage Inflammation Cytokines CNPQ::CIENCIAS DA SAUDE::FARMACIA |
topic |
Hiperuricemia Diabetes tipo 2 Doença renal do diabetes Dano tubular KIM-1 Inflamação Citocinas Hyperuricemia Type 2 diabetes Kidney disease of diabetes Tubular damage Inflammation Cytokines CNPQ::CIENCIAS DA SAUDE::FARMACIA |
description |
Hyperuricemia has emerged as a risk factor for the development of diabetes mellitus (DM) and consequently associated with the onset of diabetes kidney disease (DKD). It is known that the development of DKD is a complex process that promotes changes in different portions of the kidneys, and although hyperglycemia is a key mechanism in this process, it is not the only one. The inflammation has been evidenced as an important contributor to the pathophysiology of DKD. It is known that uric acid is a molecule that favors inflammation, both at the systemic and renal levels, contributing to kidney damage. In addition, uric acid has the potential to promote processes of afferent arteriolopathy, glomerular hypertrophy as well as direct damage to renal tubular cells. Damage to the renal tubules seems to be a primary contributor to the development of DKD and can be identified early by the presence of tubular damage markers. Despite the actions described, the mechanism by which uric acid acts in the context of DKD is not yet fully understood. Thus, the objective of this study was to evaluate the association between elevated uric acid levels and renal tubular damage, as well as its relation with renal inflammation in patients with type 2 diabetes mellitus (type 2 DM). A total of 125 patients with type 2 DM from the University Hospital of Santa Maria (HUSM), who had serum uric acid levels and other biochemical parameters measured, were recruited. In addition, urinary levels of the renal damage molecule-1 (KIM-1), used as a biomarker of tubular damage, and urinary levels of inflammatory cytokines such as interleukin-1 (IL-1), interleukin-6 ( IL- 6) and tumor necrosis factor alpha (TNF-alpha), used to check the renal inflammatory process. Patients were stratified into two groups according to the following levels of uric acid: <6.0 mg / dL and ≥6.0 mg / dL, and were compared for urinary levels of KIM-1, IL-1, IL -6 and TNF-alpha. Patients with higher serum uric acid levels were those who demonstrated higher urinary levels of KIM-1 and renal inflammation, as measured by quantification of urinary cytokines. It was also found that renal inflammation was positively correlated with the tubular damage process, as positive correlations were observed between the levels of KIM-1 and the proinflammatory cytokines evaluated in this study (IL-1, IL-6 and TNF-alpha ). Thus, we suggest that elevation of serum uric acid levels may be associated with a greater degree of tubular damage and renal inflammation in patients with type 2 DM. In addition, we believe that inflammation plays a significant role in the development of tubular renal damage and that uric acid may be promoting this inflammatory context. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-12-15 2019-09-10T19:24:41Z 2019-09-10T19:24:41Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/masterThesis |
format |
masterThesis |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://repositorio.ufsm.br/handle/1/18183 |
url |
http://repositorio.ufsm.br/handle/1/18183 |
dc.language.iso.fl_str_mv |
por |
language |
por |
dc.rights.driver.fl_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess |
rights_invalid_str_mv |
Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/ |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Farmácia UFSM Programa de Pós-Graduação em Ciências Farmacêuticas Centro de Ciências da Saúde |
publisher.none.fl_str_mv |
Universidade Federal de Santa Maria Brasil Farmácia UFSM Programa de Pós-Graduação em Ciências Farmacêuticas Centro de Ciências da Saúde |
dc.source.none.fl_str_mv |
reponame:Manancial - Repositório Digital da UFSM instname:Universidade Federal de Santa Maria (UFSM) instacron:UFSM |
instname_str |
Universidade Federal de Santa Maria (UFSM) |
instacron_str |
UFSM |
institution |
UFSM |
reponame_str |
Manancial - Repositório Digital da UFSM |
collection |
Manancial - Repositório Digital da UFSM |
repository.name.fl_str_mv |
Manancial - Repositório Digital da UFSM - Universidade Federal de Santa Maria (UFSM) |
repository.mail.fl_str_mv |
atendimento.sib@ufsm.br||tedebc@gmail.com |
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1805930229541109760 |