Avaliação da efetividade do antígeno carboidrato CA 19-9 como biomarcador em modelo experimental de obstrução parcial do trato urinário

Detalhes bibliográficos
Autor(a) principal: Shida, Márcia Emília Francisco
Data de Publicação: 2021
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações da Uninove
Texto Completo: http://bibliotecatede.uninove.br/handle/tede/3018
Resumo: Introduction: Obstructive nephropathy, resulting from urinary tract obstruction during fetal development, represents the most common cause of kidney failure in infants and children. Despite the early intrauterine diagnosis, performed by prenatal ultrasound, the determination of the prognosis of the severity of the kidney injury is not well established yet. Therefore, the identification of blood and/or urinary markers to define the progression of renal damage would play an important role in deciding on earlier and more effective therapeutic interventions. Elevated carbohydrate antigen CA19-9 (originally a tumor marker) has been described in benign urinary obstruction. Aim: This study evaluated to which extent this easy-analysis biomarker could help in the earlier diagnosis, especially in doubtful cases, of obstructive uropathies with potential renal damage. We compared it to another biomarker, Lipocalin associated with neutrophil gelatinase (Ngal), related to the severity of the obstruction. Material and method: Forty-six female Wistar rats were divided into 5 groups, with different patterns of urinary tract obstruction: group control; group OIV: infravesical obstruction; group OIVd: infravesical obstruction with reversion, relief of the obstruction on the 7th postoperative day; group OUu: unilateral ureteral obstruction; group OUb: bilateral ureteral obstruction. The determination of CA 19-9, Ngal and creatinine basal in urine and blood was performed in the rats of the groups prior to surgery (T0). Surgical interventions promoted partial obstruction depending on the group. After 13 and14 days, new measurements (T1) of the markers were taken and compared to baseline values. Group OIVd underwent an intermediate (Ti) collection before clearance. Results: There was an increase in the urinary concentration of CA19-9 in all obstructed animals. In groups OIV, OUb and OIVd, the elevation at T1 and Ti, respectively, reached statistical significance in relation to the T0 value (p≤ 0,05). Changes in urinary CA19-9 were expressive in groups with infravesical obstruction. Relief of obstruction in group OIVd promoted a significant reduction in urinary CA19-9 values in the final evaluation with AUC=0.73. There was no positive correlation between the obstructed groups and serum CA19-9 levels. Conclusions: The urinary concentration of CA19-9 increased in the presence of partial urinary tract obstruction and there was a decline in urinary CA19-9 concentration after infravesical clearance.
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spelling Queiroz, Márcia Silvahttp://lattes.cnpq.br/1927869803694015Queiroz, Márcia Silvahttp://lattes.cnpq.br/1927869803694015Dalboni, Maria Aparecidahttp://lattes.cnpq.br/9818040147487320Dellê, Humbertohttp://lattes.cnpq.br/7435662740477057Fachin, Camila Girardihttp://lattes.cnpq.br/6244472569216613Leite, Mila Torii Correahttp://lattes.cnpq.br/8864053153199325http://lattes.cnpq.br/5205911666696552Shida, Márcia Emília Francisco2022-07-27T21:50:15Z2021-11-18Shida, Márcia Emília Francisco. Avaliação da efetividade do antígeno carboidrato CA 19-9 como biomarcador em modelo experimental de obstrução parcial do trato urinário. 2021. 87 f. Tese( Programa de Mestrado em Medicina) - Universidade Nove de Julho, São Paulo.http://bibliotecatede.uninove.br/handle/tede/3018Introduction: Obstructive nephropathy, resulting from urinary tract obstruction during fetal development, represents the most common cause of kidney failure in infants and children. Despite the early intrauterine diagnosis, performed by prenatal ultrasound, the determination of the prognosis of the severity of the kidney injury is not well established yet. Therefore, the identification of blood and/or urinary markers to define the progression of renal damage would play an important role in deciding on earlier and more effective therapeutic interventions. Elevated carbohydrate antigen CA19-9 (originally a tumor marker) has been described in benign urinary obstruction. Aim: This study evaluated to which extent this easy-analysis biomarker could help in the earlier diagnosis, especially in doubtful cases, of obstructive uropathies with potential renal damage. We compared it to another biomarker, Lipocalin associated with neutrophil gelatinase (Ngal), related to the severity of the obstruction. Material and method: Forty-six female Wistar rats were divided into 5 groups, with different patterns of urinary tract obstruction: group control; group OIV: infravesical obstruction; group OIVd: infravesical obstruction with reversion, relief of the obstruction on the 7th postoperative day; group OUu: unilateral ureteral obstruction; group OUb: bilateral ureteral obstruction. The determination of CA 19-9, Ngal and creatinine basal in urine and blood was performed in the rats of the groups prior to surgery (T0). Surgical interventions promoted partial obstruction depending on the group. After 13 and14 days, new measurements (T1) of the markers were taken and compared to baseline values. Group OIVd underwent an intermediate (Ti) collection before clearance. Results: There was an increase in the urinary concentration of CA19-9 in all obstructed animals. In groups OIV, OUb and OIVd, the elevation at T1 and Ti, respectively, reached statistical significance in relation to the T0 value (p≤ 0,05). Changes in urinary CA19-9 were expressive in groups with infravesical obstruction. Relief of obstruction in group OIVd promoted a significant reduction in urinary CA19-9 values in the final evaluation with AUC=0.73. There was no positive correlation between the obstructed groups and serum CA19-9 levels. Conclusions: The urinary concentration of CA19-9 increased in the presence of partial urinary tract obstruction and there was a decline in urinary CA19-9 concentration after infravesical clearance.Introdução: A nefropatia obstrutiva, decorrente da obstrução do trato urinário durante o desenvolvimento fetal, representa a causa mais comum de insuficiência renal em bebês e crianças. Apesar do diagnóstico precoce intrauterino, realizado pela ultrassonografia pré-natal, a determinação do prognóstico da gravidade da lesão renal ainda não é bem estabelecida. Portanto, a identificação de marcadores sanguíneos e/ou urinários para definição da progressão do dano renal teria papel de importância na decisão de intervenções terapêuticas mais precoces e efetivas. A elevação do antígeno carboidrato CA19-9 (originalmente um marcador tumoral) tem sido descrita na obstrução urinária benigna. Objetivo: Este trabalho avaliou, de forma experimental, um biomarcador (CA19-9) de fácil análise, disponível na rotina da maioria dos laboratórios de análise clínicas e que poderia auxiliar no diagnóstico mais precoce, principalmente em casos duvidosos, de uropatias obstrutivas com potencial dano renal. Utilizamos, como comparador, outro biomarcador, a Lipocalina associada à gelatinase de neutrófilos (Ngal), relacionado à gravidade da obstrução. Material e método: Quarenta e seis ratas da linhagem Wistar foram divididas em cinco grupos, com diferentes padrões de obstrução parcial do trato urinário: grupo controle; grupo OIV: obstrução infravesical; grupo OIVd: obstrução infravesical com reversão e alívio da obstrução no 7o dia pós-operatório; grupo OUu: obstrução ureteral unilateral direita; grupo OUb: obstrução ureteral bilateral. A determinação basal do CA19-9, Ngal e da creatinina, na urina e no sangue, foi feita nas cobaias dos grupos previamente a cirurgia (T0). Intervenções cirúrgicas promoveram obstrução parcial dependendo do grupo. Após 13 e 14 dias novas medidas (T1) dos marcadores foram realizadas e comparadas aos valores basais. O grupo OIVd foi submetido a uma colheita intermediária prévia a desobstrução (Ti). Resultados: Houve aumento da concentração urinária do CA19-9 em todos os animais obstruídos. Nos grupos OIV, OUb e OIVd a elevação em T1 e Ti, respectivamente, atingiu significância estatística em relação ao valor de T0 (p≤ 0,05). As mudanças do CA19-9 urinário foram mais expressivas no grupo com obstrução infravesical OIV (AUC=0,81). O alívio da obstrução no grupo OIVd promoveu importante redução dos valores urinários do CA 19-9 na avaliação final com AUC=0,73. Não houve correlação positiva entre os grupos obstruídos e os níveis séricos de CA 19-9. CONCLUSÕES: A concentração urinária do CA19-9 elevou-se na presença de obstrução do trato urinário; o desempenho do CA19-9 urinário como marcador foi superior nas obstruções infravesicais (baixas) e houve um declínio da concentração urinária do CA19-9 após a desobstrução infravesical.Submitted by Nadir Basilio (nadirsb@uninove.br) on 2022-07-27T21:50:15Z No. of bitstreams: 1 Márcia Emília Francisco Shida.pdf: 3004223 bytes, checksum: 477e92cd53c13dd264ea47f9e7f196f9 (MD5)Made available in DSpace on 2022-07-27T21:50:15Z (GMT). No. of bitstreams: 1 Márcia Emília Francisco Shida.pdf: 3004223 bytes, checksum: 477e92cd53c13dd264ea47f9e7f196f9 (MD5) Previous issue date: 2021-11-18application/pdfporUniversidade Nove de JulhoPrograma de Mestrado em MedicinaUNINOVEBrasilSaúdeobstrução parcial do trato urinárioantígeno CA19-9lipocalina associada à gelatinase de neutrófilos (Ngal)ratas wistarpartial obstruction of the urinary tractCA19-9 antigenlipocalin associated with neutrophil gelatinase (Ngal)wistar ratsCIENCIAS DA SAUDEAvaliação da efetividade do antígeno carboidrato CA 19-9 como biomarcador em modelo experimental de obstrução parcial do trato urinárioEvaluation of the effectiveness of CA 19-9 carbohydrate antigen as a biomarker in an experimental model of partial obstruction of the urinary tractinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesis8765449414823306929600info:eu-repo/semantics/openAccessreponame:Biblioteca Digital de Teses e Dissertações da Uninoveinstname:Universidade Nove de Julho (UNINOVE)instacron:UNINOVEORIGINALMárcia Emília Francisco Shida.pdfMárcia Emília Francisco Shida.pdfapplication/pdf3004223http://localhost:8080/tede/bitstream/tede/3018/2/M%C3%A1rcia+Em%C3%ADlia+Francisco+Shida.pdf477e92cd53c13dd264ea47f9e7f196f9MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82165http://localhost:8080/tede/bitstream/tede/3018/1/license.txtbd3efa91386c1718a7f26a329fdcb468MD51tede/30182022-07-27 18:50:15.433oai:localhost: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Biblioteca Digital de Teses e Dissertaçõeshttp://bibliotecatede.uninove.br/PRIhttp://bibliotecatede.uninove.br/oai/requestbibliotecatede@uninove.br||bibliotecatede@uninove.bropendoar:2022-07-27T21:50:15Biblioteca Digital de Teses e Dissertações da Uninove - Universidade Nove de Julho (UNINOVE)false
dc.title.por.fl_str_mv Avaliação da efetividade do antígeno carboidrato CA 19-9 como biomarcador em modelo experimental de obstrução parcial do trato urinário
dc.title.alternative.eng.fl_str_mv Evaluation of the effectiveness of CA 19-9 carbohydrate antigen as a biomarker in an experimental model of partial obstruction of the urinary tract
title Avaliação da efetividade do antígeno carboidrato CA 19-9 como biomarcador em modelo experimental de obstrução parcial do trato urinário
spellingShingle Avaliação da efetividade do antígeno carboidrato CA 19-9 como biomarcador em modelo experimental de obstrução parcial do trato urinário
Shida, Márcia Emília Francisco
obstrução parcial do trato urinário
antígeno CA19-9
lipocalina associada à gelatinase de neutrófilos (Ngal)
ratas wistar
partial obstruction of the urinary tract
CA19-9 antigen
lipocalin associated with neutrophil gelatinase (Ngal)
wistar rats
CIENCIAS DA SAUDE
title_short Avaliação da efetividade do antígeno carboidrato CA 19-9 como biomarcador em modelo experimental de obstrução parcial do trato urinário
title_full Avaliação da efetividade do antígeno carboidrato CA 19-9 como biomarcador em modelo experimental de obstrução parcial do trato urinário
title_fullStr Avaliação da efetividade do antígeno carboidrato CA 19-9 como biomarcador em modelo experimental de obstrução parcial do trato urinário
title_full_unstemmed Avaliação da efetividade do antígeno carboidrato CA 19-9 como biomarcador em modelo experimental de obstrução parcial do trato urinário
title_sort Avaliação da efetividade do antígeno carboidrato CA 19-9 como biomarcador em modelo experimental de obstrução parcial do trato urinário
author Shida, Márcia Emília Francisco
author_facet Shida, Márcia Emília Francisco
author_role author
dc.contributor.advisor1.fl_str_mv Queiroz, Márcia Silva
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/1927869803694015
dc.contributor.referee1.fl_str_mv Queiroz, Márcia Silva
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/1927869803694015
dc.contributor.referee2.fl_str_mv Dalboni, Maria Aparecida
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/9818040147487320
dc.contributor.referee3.fl_str_mv Dellê, Humberto
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/7435662740477057
dc.contributor.referee4.fl_str_mv Fachin, Camila Girardi
dc.contributor.referee4Lattes.fl_str_mv http://lattes.cnpq.br/6244472569216613
dc.contributor.referee5.fl_str_mv Leite, Mila Torii Correa
dc.contributor.referee5Lattes.fl_str_mv http://lattes.cnpq.br/8864053153199325
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/5205911666696552
dc.contributor.author.fl_str_mv Shida, Márcia Emília Francisco
contributor_str_mv Queiroz, Márcia Silva
Queiroz, Márcia Silva
Dalboni, Maria Aparecida
Dellê, Humberto
Fachin, Camila Girardi
Leite, Mila Torii Correa
dc.subject.por.fl_str_mv obstrução parcial do trato urinário
antígeno CA19-9
lipocalina associada à gelatinase de neutrófilos (Ngal)
ratas wistar
topic obstrução parcial do trato urinário
antígeno CA19-9
lipocalina associada à gelatinase de neutrófilos (Ngal)
ratas wistar
partial obstruction of the urinary tract
CA19-9 antigen
lipocalin associated with neutrophil gelatinase (Ngal)
wistar rats
CIENCIAS DA SAUDE
dc.subject.eng.fl_str_mv partial obstruction of the urinary tract
CA19-9 antigen
lipocalin associated with neutrophil gelatinase (Ngal)
wistar rats
dc.subject.cnpq.fl_str_mv CIENCIAS DA SAUDE
description Introduction: Obstructive nephropathy, resulting from urinary tract obstruction during fetal development, represents the most common cause of kidney failure in infants and children. Despite the early intrauterine diagnosis, performed by prenatal ultrasound, the determination of the prognosis of the severity of the kidney injury is not well established yet. Therefore, the identification of blood and/or urinary markers to define the progression of renal damage would play an important role in deciding on earlier and more effective therapeutic interventions. Elevated carbohydrate antigen CA19-9 (originally a tumor marker) has been described in benign urinary obstruction. Aim: This study evaluated to which extent this easy-analysis biomarker could help in the earlier diagnosis, especially in doubtful cases, of obstructive uropathies with potential renal damage. We compared it to another biomarker, Lipocalin associated with neutrophil gelatinase (Ngal), related to the severity of the obstruction. Material and method: Forty-six female Wistar rats were divided into 5 groups, with different patterns of urinary tract obstruction: group control; group OIV: infravesical obstruction; group OIVd: infravesical obstruction with reversion, relief of the obstruction on the 7th postoperative day; group OUu: unilateral ureteral obstruction; group OUb: bilateral ureteral obstruction. The determination of CA 19-9, Ngal and creatinine basal in urine and blood was performed in the rats of the groups prior to surgery (T0). Surgical interventions promoted partial obstruction depending on the group. After 13 and14 days, new measurements (T1) of the markers were taken and compared to baseline values. Group OIVd underwent an intermediate (Ti) collection before clearance. Results: There was an increase in the urinary concentration of CA19-9 in all obstructed animals. In groups OIV, OUb and OIVd, the elevation at T1 and Ti, respectively, reached statistical significance in relation to the T0 value (p≤ 0,05). Changes in urinary CA19-9 were expressive in groups with infravesical obstruction. Relief of obstruction in group OIVd promoted a significant reduction in urinary CA19-9 values in the final evaluation with AUC=0.73. There was no positive correlation between the obstructed groups and serum CA19-9 levels. Conclusions: The urinary concentration of CA19-9 increased in the presence of partial urinary tract obstruction and there was a decline in urinary CA19-9 concentration after infravesical clearance.
publishDate 2021
dc.date.issued.fl_str_mv 2021-11-18
dc.date.accessioned.fl_str_mv 2022-07-27T21:50:15Z
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dc.identifier.citation.fl_str_mv Shida, Márcia Emília Francisco. Avaliação da efetividade do antígeno carboidrato CA 19-9 como biomarcador em modelo experimental de obstrução parcial do trato urinário. 2021. 87 f. Tese( Programa de Mestrado em Medicina) - Universidade Nove de Julho, São Paulo.
dc.identifier.uri.fl_str_mv http://bibliotecatede.uninove.br/handle/tede/3018
identifier_str_mv Shida, Márcia Emília Francisco. Avaliação da efetividade do antígeno carboidrato CA 19-9 como biomarcador em modelo experimental de obstrução parcial do trato urinário. 2021. 87 f. Tese( Programa de Mestrado em Medicina) - Universidade Nove de Julho, São Paulo.
url http://bibliotecatede.uninove.br/handle/tede/3018
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dc.publisher.none.fl_str_mv Universidade Nove de Julho
dc.publisher.program.fl_str_mv Programa de Mestrado em Medicina
dc.publisher.initials.fl_str_mv UNINOVE
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Saúde
publisher.none.fl_str_mv Universidade Nove de Julho
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