Association of sepsis-related mortality with early increase of TIMP-1/MMP-9 ratio

Lorente, L. ; Martín, M. M. ; Solé-Violn, J. ; Blanquer, J. ; Labarta, L. (Universidad de Zaragoza) ; Díaz, C. ; Borreguero-León, J. M. ; Orbe, J. ; Rodríguez, J. A. ; Jiménez, A. ; Páramo, J. A.

Resumen: Objective: Higher circulating levels of tissue inhibitor of matrix metalloproteinases (TIMP)-1 at the time of severe sepsis diagnosis have been reported in nonsurviving than in surviving patients. However, the following questions remain unanswered: 1) Does TIMP-1/MMP-9 ratio differ throughout the first week of intensive care between surviving and nonsurviving patients? 2) Is there an association between TIMP-1/MMP-9 ratio and sepsis severity and mortality during such period? 3) Could TIMP-1/MMP-9 ratio during the first week be used as an early biomarker of sepsis outcome? 4) Is there an association between TIMP-1/MMP-9 ratio and coagulation state and circulating cytokine levels during the first week of intensive care in these patients? The present study sought to answer these questions. Methods: Multicenter, observational and prospective study carried out in six Spanish Intensive Care Units (ICUs) of 295 patients with severe sepsis. Were measured circulating levels of TIMP-1, MMP-9, tumour necrosis factor (TNF)-alpha, interleukin (IL)-10 and plasminogen activator inhibitor (PAI)-1 at day 1, 4 and 8. End-point was 30-day mortality. Results: We found higher TIMP-1/MMP-9 ratio during the first week in non-surviving (n = 98) than in surviving patients (n = 197) (p, 0.01). Logistic regression analyses showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 was associated with mortality. Receiver operating characteristic (ROC) curves showed that TIMP-1/MMP-9 ratio at days 1, 4 and 8 could predict mortality. There was an association between TIMP-1/MMP-9 ratio and TNF-alpha, IL-10, PAI-1 and lactic acid levels, SOFA score and platelet count at days 1, 4 and 8. Conclusions: The novel findings of our study were that non-surviving septic patients showed persistently higher TIMP-1/ MMP-9 ratio than survivors ones during the first week, which was associated with severity, coagulation state, circulating cytokine levels and mortality; thus representing a new biomarker of sepsis outcome.

Idioma: Inglés

DOI: 10.1371/journal.pone.0094318

Año: 2014

Publicado en: PLoS One 9, 4 (2014), e94318 [7 pp]
ISSN: 1932-6203

Factor impacto JCR: 3.234 (2014)

Categ. JCR: MULTIDISCIPLINARY SCIENCES rank: 9 / 57 = 0.158 (2014) - Q1 - T1

Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI10-01572
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/I3SNS-INT-11-063
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/I3SNS-INT-12-087

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Medicina (Departamento de Medicina, Psiquiatría y Dermatología)