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Doctoral Thesis
DOI
10.11606/T.5.2009.tde-09062009-172844
Document
Author
Full name
Amanda Francisco Martins
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2009
Supervisor
Committee
Yu, Luis (President)
Burdmann, Emmanuel de Almeida
Homsi, Eduardo
Santos, Bento Fortunato Cardoso dos
Seguro, Antonio Carlos
Title in Portuguese
Avaliação de marcadores de inflamação em pacientes com lesão renal aguda em unidade de terapia intensiva
Keywords in Portuguese
Citocinas
Estudos de casos e controles
Inflamação
Insuficiência renal aguda
Unidades de terapia intensiva
Abstract in Portuguese
A incidência de lesão renal aguda (LRA) em Unidade de Terapia Intensiva (UTI) é de 5 a 25% e está associada a elevada mortalidade. A intensidade da resposta inflamatória reflete a magnitude do processo fisiopatológico da LRA e parece estar relacionada a um aumento na gravidade desses pacientes. Os objetivos desse estudo foram: a) avaliar o nível de mediadores inflamatórios em pacientes críticos com LRA; b) avaliar o perfil desses mediadores em conjunto com parâmetros clínicos e laboratoriais, comparando pacientes críticos com e sem LRA; c) avaliar o impacto desses mediadores na sobrevida dos pacientes. Foi realizado um estudo observacional, prospectivo, do tipo caso-controle, em quatro UTIs do HCFMUSP no período entre novembro de 2006 e março de 2008. LRA foi definida segundo a classificação de RIFLE. Foram realizadas dosagens séricas dos seguintes marcadores: fator de necrose tumoral- (TNF-), receptor solúvel do tipo 1 do TNF- (sTNFR1), interleucina (IL)-6, IL-8, IL-10, leptina e proteína C-reativa (PCR). Os mediadores foram dosados no dia do diagnóstico de LRA (D1), dois dias após o D1, denominado D3 e quatro dias após o D1, denominado D5. A população final de análise foi composta por 52 pacientes no grupo caso e 9 pacientes no grupo controle. No D1, os níveis séricos de IL-6 estavam significativamente mais elevados nos pacientes com LRA: 61,68 (14,30 389,11) pg/mL versus 13,21 (1,50 47,06) pg/mL (p=0,032). Da mesma forma, os níveis de TNF-: 3,22 (0,57 xvi 15,9) pg/mL nos pacientes com LRA versus 0,32 (0,32 0,34) pg/mL nos controles (p<0,001). Os níveis séricos de sTNFR1 dosados, neste primeiro dia, foi significativamente menor no grupo LRA: 554,48 (459,48 770,61) pg/mL versus 768,82 (590,78 840,86) pg/mL no grupo controle, (p=0,035). No D3, os níveis séricos de TNF- mantiveram-se mais elevados, 4,64 (1,10 11,81) pg/mL versus 0,32 (0,32 0,34) pg/mL (p<0,001). Após análise de regressão logística, a dosagem mais elevada de TNF-, no D1, permaneceu como fator independente associado a LRA. Dentre os pacientes do grupo LRA, os marcadores inflamatórios que tiveram valor preditivo para menor sobrevida, quando dosados no D1, foram: PCR maior ou igual a 80 mg/dL, 39±6,7 dias versus 42±8,1 dias (p=0,023); IL-8 maior ou igual a 77 pg/mL, 25±11,4 dias versus 42±15,7 dias (p=0,037); IL-10 maior ou igual a 90 pg/mL, 24±9,2 dias versus 39±5,7 dias (p=0,029) e sTNFR1 menor ou igual a 540 pg/mL, 29±6,7 dias versus 39±5,7 dias (p=0,029). Após análise de regressão proporcional de Cox, IL-10 e sTNFR1 permaneceram como preditores independentes de menor sobrevida entre os pacientes com LRA. Na população analisada, o perfil de citocinas nos pacientes com LRA sugere um aumento da resposta imunológica pró-inflamatória, já no dia do diagnóstico da LRA, sendo TNF- um marcador de LRA neste dia. O perfil de citocinas preditoras de sobrevida em pacientes com LRA sugere o envolvimento da resposta imunológica anti-inflamatória na menor sobrevida destes pacientes, sendo sTNFR1 e IL-10 preditores independentes de menor sobrevida em pacientes críticos com LRA
Title in English
Assessement of inflammatory mediators in critically ill AKI patients
Keywords in English
Case-control studies
Cytokines
Inflammation
Intensive care units
Renal insufficiency acute
Abstract in English
The incidence of Acute Kidney Injury (AKI) in Intensive Care Units (ICU) ranges between 5 and 25% and is associated with an increased mortality. The degree of the inflammatory response reflects the severity of the physiopathologic process involved in AKI which appears to be correlated to the underline severity of the disease in these patients. The aims of this study were: a) evaluate serum level of inflammatory mediators in AKI critically ill patients; b) assess the pattern of these inflammatory mediators in addition to some others clinical and laboratory parameters, in order to compare these values in patients with and without AKI; c) correlate the serum level of these inflammatory markers and patient survival. We conduct a prospective, observational, case-control study in four ICUs at Clinic Hospital of University of Sao Paulo from November 2006 to March 2008. AKI was defined based on the RIFLE classification system. The following inflammatory mediators were measured in the serum: tumor necrosis factor-alpha (TNF-), soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin (IL) -6, IL-8, IL-10, leptin e C-reactive protein (PCR). The inflammatory mediators were measured in the day of AKI diagnosis (D1), two and four days after the diagnosis, named D3 and D5, respectively. We analyzed 52 AKI patients and 9 controls. In D1 serum levels of IL-6 were significantly higher in AKI patients: 61.68 (14.30 389.11) pg/mL vs 13.21 (1.50 47.06) pg/mL in controls (p=0.032). Also the serum levels of TNF- were higher in AKI patients; 3.22 (0.57 15.9) pg/mL vs 0.32 (0.32 0.34) pg/mL in controls (p<0.001). The serum levels of sTNFR1 in the first day were significantly lower in the AKI group; 554.48 (459.48 770.61) pg/mL vs 768.82 (590.78 840.86) pg/mL in controls, (p=0.035). In D3, the serum levels of TNF- were still higher, 4.64 (1.10 11.81) pg/mL vs 0.32 (0.32 0.34) pg/mL (p<0.001). After logistic regression, the higher serum levels of TNF- remained as independent factor associated to AKI. Among the AKI patients, the inflammatory mediators that were predictive of survival in the first day were: PCR 80 mg/dL, 39±6.7 days vs 42±8.1 days (p=0.023); IL-8 77 pg/mL, 25±11.4 days vs 42±15.7 days (p=0.037); IL-10 90 pg/mL, 24±9.2 days vs 39±5.7 days (p=0.029) and sTNFR1 540 pg/mL, 29±6.7 days vs 39±5.7 days (p=0.029). After Cox proportional hazards survival regression, IL-10 and sTNFR1 remained as independent predictors of lower survival among patients with AKI. In the population studied, the pattern of cytokines in patients presenting AKI suggests an elevated pro-inflammatory immunologic response since AKI diagnosis. TNF- was the AKI marker in this first day. The pattern of cytokines related to AKI point to the role of immunologic anti-inflammatory response on the lower survival of these patients. The higher levels of sTNFR1 and IL-10 were independent factors associated with lower survival rates in AKI critically ill patients
 
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Publishing Date
2009-06-30
 
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