Doença por citomegalovírus em transplantados renais: características clínicas e cinética da carga viral

Detalhes bibliográficos
Autor(a) principal: Cavalcante, Samuel de Alencar [UNIFESP]
Data de Publicação: 2018
Tipo de documento: Tese
Idioma: por
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=6443089
https://repositorio.unifesp.br/handle/11600/52549
Resumo: Cytomegalovirus (CMV) is one of the main responsible for opportunistic infections in renal transplantation, associated with important morbidity and mortality. Knowledge about the particularity of viral kinetics may help in the clinical management of renal transplants and to obtain a better cost-effectiveness in the use of prevention therapies. Therefore, the aim of this study was to evaluate the cytomegalovirus (CMV) viral kinetics in renal transplant patients with and without CMV disease. This is a longitudinal study with follow-up of 90 days after transplantation developed at the general transplantation unit (UGT) and at the AC Hart Translational Research Laboratory in IMIP, from April / 2015 to July / 2016, and included 100 patients who underwent cadaveric or live donor kidney transplantation using thymoglobulin and absence of prevention strategies (prophylaxis or preemptive). Blood samples were collected before transplantation and 14, 21, 30, 45, 60, 75, 90 days after transplantation. The CMV viral load was determined by real-time Polymerase Chain Reaction (PCR), and the results expressed in log 10 and IU / mL. The Receiver Operating Characteristic (ROC) curve was used to calculate the best values of the CMV viral load associated with the occurrence of CMV disease, according to the highest accuracy value obtained. For statistical analysis, the program GraphPad Prism 7.0 was used, and considered significant p<0.05. The frequency of CMV disease was 61%, with a mean initial viral load of log10 5.54 or 346,736 IU/mL, median time to anti-CMV treatment was 35.8 days, and clinical recurrence was 13%. The days 30 and 45 after transplantation were the periods with the highest detection of CMV in the group of patients who develoled CMV disease when compared to those who did not developed (p = 0.001 and p <0.0001, respectively). Highers levels of viral load were observed in patients with disease when compared to those without CMV disease in the 21 (p = 0.01), 30 (p = 0.03), 45 (p = 0.001) and 60 (p = 0.01) days after renal transplantation. Viral load kinetics in patients with CMV disease showed exponential growth, with a higher peak at 45 days. Asymptomatic viremias were present in 36% of the patients, with viral load between log10 3.9 - 4.1 from 30 until 90 days after transplantation. A ROC curve with area of 0.77 (95% CI: 0.66- 0.87; p <0.0001) was obtained. The CMV viral load with log10 4.18 (15,135 IU/mL) showed better sensitivity and specificity (70% and 81%, respectively) for the diagnosis of CMV disease. It was observed that the CMV viral load in the patients using cyclosporin was elevated when compared to the tacrolimus and m-TOR inhibitor (p = 0.01). CMV disease showed a high frequency in transplants using thymoglobulin induction and in the absence of prevention strategies, with no impact on mortality. Stable CMV load levels in asymptomatic viremias in most periods after transplantation suggest that preemptive therapy is unnecessary with qPCR log10 <4.0.
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spelling Doença por citomegalovírus em transplantados renais: características clínicas e cinética da carga viralCytomegalovirus disease in kidney transplant recipients: clinical characteristics and viral load kineticsCytomegalovirusKidney transplantationPolymerase chain reactionViral loadCitomegalovirusTransplante de rimReação em cadeia da polimeraseCarga viralCytomegalovirus (CMV) is one of the main responsible for opportunistic infections in renal transplantation, associated with important morbidity and mortality. Knowledge about the particularity of viral kinetics may help in the clinical management of renal transplants and to obtain a better cost-effectiveness in the use of prevention therapies. Therefore, the aim of this study was to evaluate the cytomegalovirus (CMV) viral kinetics in renal transplant patients with and without CMV disease. This is a longitudinal study with follow-up of 90 days after transplantation developed at the general transplantation unit (UGT) and at the AC Hart Translational Research Laboratory in IMIP, from April / 2015 to July / 2016, and included 100 patients who underwent cadaveric or live donor kidney transplantation using thymoglobulin and absence of prevention strategies (prophylaxis or preemptive). Blood samples were collected before transplantation and 14, 21, 30, 45, 60, 75, 90 days after transplantation. The CMV viral load was determined by real-time Polymerase Chain Reaction (PCR), and the results expressed in log 10 and IU / mL. The Receiver Operating Characteristic (ROC) curve was used to calculate the best values of the CMV viral load associated with the occurrence of CMV disease, according to the highest accuracy value obtained. For statistical analysis, the program GraphPad Prism 7.0 was used, and considered significant p<0.05. The frequency of CMV disease was 61%, with a mean initial viral load of log10 5.54 or 346,736 IU/mL, median time to anti-CMV treatment was 35.8 days, and clinical recurrence was 13%. The days 30 and 45 after transplantation were the periods with the highest detection of CMV in the group of patients who develoled CMV disease when compared to those who did not developed (p = 0.001 and p <0.0001, respectively). Highers levels of viral load were observed in patients with disease when compared to those without CMV disease in the 21 (p = 0.01), 30 (p = 0.03), 45 (p = 0.001) and 60 (p = 0.01) days after renal transplantation. Viral load kinetics in patients with CMV disease showed exponential growth, with a higher peak at 45 days. Asymptomatic viremias were present in 36% of the patients, with viral load between log10 3.9 - 4.1 from 30 until 90 days after transplantation. A ROC curve with area of 0.77 (95% CI: 0.66- 0.87; p <0.0001) was obtained. The CMV viral load with log10 4.18 (15,135 IU/mL) showed better sensitivity and specificity (70% and 81%, respectively) for the diagnosis of CMV disease. It was observed that the CMV viral load in the patients using cyclosporin was elevated when compared to the tacrolimus and m-TOR inhibitor (p = 0.01). CMV disease showed a high frequency in transplants using thymoglobulin induction and in the absence of prevention strategies, with no impact on mortality. Stable CMV load levels in asymptomatic viremias in most periods after transplantation suggest that preemptive therapy is unnecessary with qPCR log10 <4.0.O citomegalovírus (CMV) é um dos principais responsáveis pelas infecções oportunistas em transplante renal, associado com importante morbimortalidade. O conhecimento sobre a particularidade da cinética viral pode ajudar no manejo clínico dos transplantados renais, a fim de obter um melhor custo efetividade no uso das terapias de prevenção. Portanto, objetivo deste estudo foi avaliar a cinética viral do citomegalovírus (CMV) nos pacientes transplantados renais com e sem doença por CMV. Trata-se de um estudo de longitudinal com seguimento de 90 dias após transplante. O estudo foi realizado na unidade geral de transplantes e no Laboratório de Pesquisa Translacional A.C. Hart do IMIP entre os períodos de abril/2015 a julho/2016, sendo incluídos 100 pacientes submetidos a transplante renal doador cadáver ou vivo, em uso de timoglobulina e na ausência de estratégias de prevenção (profilaxia ou preemptivo). Amostras sanguíneas foram coletadas antes do transplante e 14, 21, 30, 45, 60, 75, 90 dias após o transplante. A carga viral de CMV foi determinada por Polymerase Chain Reaction (PCR) em tempo real, e os resultados expressos em logaritmo 10 e UI/mL. A curva Receiver Operating Characteristic (ROC) foi realizada para cálculo dos melhores valores da carga viral de CMV associado com a ocorrência de doença por CMV, de acordo com o valor de maior acurácia obtido. Para análises estatísticas, foi utilizado o programa GraphPad Prism 7.0, e considerado significativo p<0.05. A frequência de doença por CMV foi de 61%, com média de carga viral inicial log 5.54 ou 346.736 UI/mL, e mediana do tempo de tratamento anti-CMV foi 35,8 dias, e a recidiva clínica foi em 13% dos pacientes. Os dias 30 e 45 após o transplante foram os períodos com maior detecção de CMV no grupo de pacientes que evoluíram para doença quando comparado aos que não evoluíram (p=0,001 e p<0,0001, respectivamente). Foi observado elevados níveis de carga viral nos pacientes com doença quando comparado aos sem doença por CMV nos períodos de 21 (p=0,01), 30 (p=0,03), 45 (p=0,001) e 60 (p=0,01) dias após transplante renal. A cinética da carga viral nos pacientes com doença por CMV teve crescimento exponencial, com um maior pico aos 45 dias. As viremias assintomáticas estiveram presentes em 36% dos pacientes, com carga viral entre log 3,9 - 4,1 partir dos 30 e até os 90 dias após transplante. Obteve-se uma curva ROC com área de 0,77 (IC 95%: 0,66-0,87; p<0,0001). A carga viral do CMV com log de 4,18 (15.135 UI/mL) apresentou melhor sensibilidade e especificidade (70% e 81%, respectivamente) para o diagnóstico de doença por CMV Observou-se que a carga viral de CMV nos pacientes utilizando ciclosporina foi elevada quando comparado aos grupos com tacrolimo e inibidores da m-TOR (p=0,01). A doença por CMV apresentou uma frequência elevada nos transplantados em uso de indução de timoglobulina e na ausência de estratégias de prevenção, sem impacto na mortalidade. Os níveis das cargas do CMV estáveis nas viremias assintomáticas na maioria dos períodos após transplante, sugere ser desnecessário tratamento preemptivo qPCR log < 4.0.Dados abertos - Sucupira - Teses e dissertações (2018)Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco (FACEPE)FACEPE: Processo APQ – 351-4.01/11Universidade Federal de São Paulo (UNIFESP)Pestana, Jose Osmar Medina De Abreu [UNIFESP]Silva Junior, Helio Tedesco [UNIFESP]Torres, Leuridan Cavalcantehttp://lattes.cnpq.br/1621797721074970http://lattes.cnpq.br/7250195328752808http://lattes.cnpq.br/1551824344150025Universidade Federal de São Paulo (UNIFESP)Cavalcante, Samuel de Alencar [UNIFESP]2020-03-25T11:44:02Z2020-03-25T11:44:02Z2018-11-28info:eu-repo/semantics/doctoralThesisinfo:eu-repo/semantics/publishedVersion96 f.application/pdfhttps://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=6443089Tese - versão final - Samuel de Alencar Cavalcante.pdfhttps://repositorio.unifesp.br/handle/11600/52549porSão Pauloinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-10T12:48:42Zoai:repositorio.unifesp.br/:11600/52549Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-08-10T12:48:42Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Doença por citomegalovírus em transplantados renais: características clínicas e cinética da carga viral
Cytomegalovirus disease in kidney transplant recipients: clinical characteristics and viral load kinetics
title Doença por citomegalovírus em transplantados renais: características clínicas e cinética da carga viral
spellingShingle Doença por citomegalovírus em transplantados renais: características clínicas e cinética da carga viral
Cavalcante, Samuel de Alencar [UNIFESP]
Cytomegalovirus
Kidney transplantation
Polymerase chain reaction
Viral load
Citomegalovirus
Transplante de rim
Reação em cadeia da polimerase
Carga viral
title_short Doença por citomegalovírus em transplantados renais: características clínicas e cinética da carga viral
title_full Doença por citomegalovírus em transplantados renais: características clínicas e cinética da carga viral
title_fullStr Doença por citomegalovírus em transplantados renais: características clínicas e cinética da carga viral
title_full_unstemmed Doença por citomegalovírus em transplantados renais: características clínicas e cinética da carga viral
title_sort Doença por citomegalovírus em transplantados renais: características clínicas e cinética da carga viral
author Cavalcante, Samuel de Alencar [UNIFESP]
author_facet Cavalcante, Samuel de Alencar [UNIFESP]
author_role author
dc.contributor.none.fl_str_mv Pestana, Jose Osmar Medina De Abreu [UNIFESP]
Silva Junior, Helio Tedesco [UNIFESP]
Torres, Leuridan Cavalcante
http://lattes.cnpq.br/1621797721074970
http://lattes.cnpq.br/7250195328752808
http://lattes.cnpq.br/1551824344150025
Universidade Federal de São Paulo (UNIFESP)
dc.contributor.author.fl_str_mv Cavalcante, Samuel de Alencar [UNIFESP]
dc.subject.por.fl_str_mv Cytomegalovirus
Kidney transplantation
Polymerase chain reaction
Viral load
Citomegalovirus
Transplante de rim
Reação em cadeia da polimerase
Carga viral
topic Cytomegalovirus
Kidney transplantation
Polymerase chain reaction
Viral load
Citomegalovirus
Transplante de rim
Reação em cadeia da polimerase
Carga viral
description Cytomegalovirus (CMV) is one of the main responsible for opportunistic infections in renal transplantation, associated with important morbidity and mortality. Knowledge about the particularity of viral kinetics may help in the clinical management of renal transplants and to obtain a better cost-effectiveness in the use of prevention therapies. Therefore, the aim of this study was to evaluate the cytomegalovirus (CMV) viral kinetics in renal transplant patients with and without CMV disease. This is a longitudinal study with follow-up of 90 days after transplantation developed at the general transplantation unit (UGT) and at the AC Hart Translational Research Laboratory in IMIP, from April / 2015 to July / 2016, and included 100 patients who underwent cadaveric or live donor kidney transplantation using thymoglobulin and absence of prevention strategies (prophylaxis or preemptive). Blood samples were collected before transplantation and 14, 21, 30, 45, 60, 75, 90 days after transplantation. The CMV viral load was determined by real-time Polymerase Chain Reaction (PCR), and the results expressed in log 10 and IU / mL. The Receiver Operating Characteristic (ROC) curve was used to calculate the best values of the CMV viral load associated with the occurrence of CMV disease, according to the highest accuracy value obtained. For statistical analysis, the program GraphPad Prism 7.0 was used, and considered significant p<0.05. The frequency of CMV disease was 61%, with a mean initial viral load of log10 5.54 or 346,736 IU/mL, median time to anti-CMV treatment was 35.8 days, and clinical recurrence was 13%. The days 30 and 45 after transplantation were the periods with the highest detection of CMV in the group of patients who develoled CMV disease when compared to those who did not developed (p = 0.001 and p <0.0001, respectively). Highers levels of viral load were observed in patients with disease when compared to those without CMV disease in the 21 (p = 0.01), 30 (p = 0.03), 45 (p = 0.001) and 60 (p = 0.01) days after renal transplantation. Viral load kinetics in patients with CMV disease showed exponential growth, with a higher peak at 45 days. Asymptomatic viremias were present in 36% of the patients, with viral load between log10 3.9 - 4.1 from 30 until 90 days after transplantation. A ROC curve with area of 0.77 (95% CI: 0.66- 0.87; p <0.0001) was obtained. The CMV viral load with log10 4.18 (15,135 IU/mL) showed better sensitivity and specificity (70% and 81%, respectively) for the diagnosis of CMV disease. It was observed that the CMV viral load in the patients using cyclosporin was elevated when compared to the tacrolimus and m-TOR inhibitor (p = 0.01). CMV disease showed a high frequency in transplants using thymoglobulin induction and in the absence of prevention strategies, with no impact on mortality. Stable CMV load levels in asymptomatic viremias in most periods after transplantation suggest that preemptive therapy is unnecessary with qPCR log10 <4.0.
publishDate 2018
dc.date.none.fl_str_mv 2018-11-28
2020-03-25T11:44:02Z
2020-03-25T11:44:02Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/doctoralThesis
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Tese - versão final - Samuel de Alencar Cavalcante.pdf
https://repositorio.unifesp.br/handle/11600/52549
url https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=6443089
https://repositorio.unifesp.br/handle/11600/52549
identifier_str_mv Tese - versão final - Samuel de Alencar Cavalcante.pdf
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dc.publisher.none.fl_str_mv Universidade Federal de São Paulo (UNIFESP)
publisher.none.fl_str_mv Universidade Federal de São Paulo (UNIFESP)
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
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reponame_str Repositório Institucional da UNIFESP
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