RESUMEN
Acute kidney injury (AKI) during sepsis is common and underestimated. Plasma neutrophil gelatinase-associated lipocalin (plasma-NGAL) is discussed as new biomarker for AKI diagnosis, but during inflammation its function and diagnostic impact remain unclear. The association between plasma-NGAL and inflammatory markers in septic patients, but also in healthy controls and patients with chronic inflammation before and after either maximum exercise test or treatment with an anti-TNF therapy were investigated. In-vitro blood stimulations with IL-6, lipopolysaccharide, NGAL or its combinations were performed to investigate cause-effect-relationship. Plasma-NGAL levels were stronger associated with inflammation markers including IL-6 (Sepsis: r = 0.785 P < 0.001; chronic inflammation after anti-TNF: r = 0.558 P < 0.001), IL-8 (Sepsis: r = 0.714 P<0.004; healthy controls after exercise r = 0.786 P < 0.028; chronic inflammation before anti-TNF: r = 0.429 P < 0.041) and IL-10 (healthy controls before exercise: r = 0.791 P < 0.028) than with kidney injury or function. Correlation to kidney injury or function was found only in septic patients (for creatinine: r = 0.906 P < 0.001; for eGFR: r = -0.686 P = 0.005) and in patients with rheumatic disease after anti-TNF therapy (for creatinine: r = 0.466 P < 0.025). In stimulation assays with IL-6 and lipopolysaccharide plasma-NGAL was increased. Co-stimulation of lipopolysaccharide with plasma-NGAL decreased cellular injury (P < 0.05) and in trend IL-10 levels (P = 0.057). Septic mice demonstrated a significantly improved survival rate after NGAL treatment (P < 0.01). Plasma-NGAL seams to be strongly involved in inflammation. For clinical relevance, it might not only be useful for AKI detection during severe inflammation - indeed it has to be interpreted carefully within this setting - but additionally might offer therapeutic potential.
Asunto(s)
Inflamación/sangre , Lipocalinas/sangre , Proteínas Oncogénicas/sangre , Proteínas Proto-Oncogénicas/sangre , Sepsis/sangre , Proteínas de Fase Aguda , Adulto , Anciano , Animales , Biomarcadores/sangre , Ejercicio Físico , Femenino , Tasa de Filtración Glomerular , Humanos , Interleucina-10/sangre , Interleucina-6/sangre , Estimación de Kaplan-Meier , Riñón/lesiones , Riñón/metabolismo , Lipocalina 2 , Lipopolisacáridos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Distribución Aleatoria , Enfermedades Reumáticas/metabolismo , Sepsis/fisiopatología , Investigación Biomédica TraslacionalRESUMEN
In experimental studies, the importance of aldosterone for the development of left ventricular (LV) hypertrophy has been demonstrated. In 120 healthy Caucasian men (aged 25 +/- 3 years; blood pressure, 134 +/- 15/86 +/- 12 mm Hg), we determined LV mass (2-dimensionally guided M-mode echocardiography), urinary aldosterone concentration, and the response of aldosterone to angiotensin II infusion (3.0 ng/kg/min). Seventy-six volunteers took part in a follow-up visit after 2 years when urinary aldosterone concentration and LV mass were determined again. At follow-up, LV mass increased in 42 subjects (by 33 +/- 26 g), whereas in 34 subjects LV mass decreased (by 27 +/- 22 g). Between the 2 groups, only the change in urinary aldosterone concentration over time was significantly different (group with increased LV mass had an increase in urinary aldosterone concentration by 2.5 +/- 5.4 microg/day; group with decreased LV mass had a decrease in urinary aldosterone concentration by 0.7 +/- 4.6; p <0.01 between groups). In accordance, we found significant correlations between changes in LV mass and changes in urinary aldosterone concentration (r = 0.29, p <0.05) and between changes in LV mass and the response of aldosterone to angiotensin II at baseline (r = 0.25, p <0.05). Both changes in aldosterone concentration over time and the response of aldosterone to angiotensin II were related to changes in LV mass over time. These data underscore the importance of aldosterone for the development of LV hypertrophy. This process is already evident in young subjects with apparently small changes in LV mass over a mean follow-up period of 2 years.