Introduction: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising novel biomarker that correlates with the severity and outcome of acute kidney injury (AKI). However, its prognostic utility during the late course of AKI, especially in patients that require renal replacement therapy (RRT) remains unknown. The aim of this study was to evaluate the predictive value of serum NGAL in patients with established AKI at inception of RRT in the intensive care unit (ICU). Methods: Serum NGAL (ELISA methodology) was measured in 109 critically ill patients with AKI at inception of RRT in 7 ICUs of a tertiary care university hospital. The primary outcome studied was 28-day mortality. Secondary outcome measures were ICU length of stay, ventilator-free days, and renal recovery at day 28. Results: There was a significant difference in serum NGAL between healthy subjects (median [interquartile range] 39.0 [37.5-42.75] ng/mL), critically ill patients with systemic inflammatory response syndrome (SIRS) (297 [184-490] ng/mL), and critically ill patients with sepsis (708 [365-1301] ng/mL; P < 0.0001), respectively. Multiple linear regression showed that NGAL levels were independently related to the severity of AKI and the extent of systemic inflammation. NGAL levels were higher in non-survivors (430 [303-942] ng/mL) compared to survivors (298 [159-506] ng/mL; P = 0.004). Consistently, Cox proportional hazards regression analysis identified NGAL as a strong independent predictor for 28-day survival (hazard ratio 1.6 (95% confidence interval [CI] 1.15 - 2.23), P = 0.005). Conclusions: This is the first prospective evaluation of serum NGAL as an outcome-specific biomarker in critically ill patients at initiation of RRT. The results from this study indicate that serum NGAL is as an independent predictor of 28-day mortality in ICU patients with dialysis-dependent AKI.

Background: Early inflammation has been suggested as an important factor contributing to unfavorable prognosis after acute ischemic stroke. The present study aimed to clarify the temporal dynamics of discrete inflammatory markers/mediators for future mechanism-targeting anti-inflammatory strategies in ischemic brain damage. Methods: Blood samples of 69 patients with transient ischemic attack or ischemic stroke were taken upon admission and at time points 6, 12 and 24 h, as well as 3 and 7 days after symptom onset for analysis of monocyte chemotactic protein-1 (MCP-1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), interleukin-6 (IL-6), C-reactive protein (CRP) and the brain damage marker S100B. Clinical scores (modified Rankin Scale, National Institute of Health Stroke Scale) were assessed on day 90. Results: MCP-1, MMP-9, TIMP-1, IL-6, CRP and S100B showed significantly different time courses depending on stroke outcome. While the levels of IL-6, MCP-1 and MMP-9 increased already a few hours after symptom onset, CRP and S100B gradually rose commencing at 12–24 h. TIMP-1 demonstrated an extended plateau. By multiple linear regression analysis IL-6, MCP-1, TIMP-1 and S100B were determined to be independently related to clinical outcome scores at specific time points. Conclusions: Our data show important differences in the early time course of several potential markers for the complex network of inflammation and brain damage after ischemic stroke depending on stroke outcome. This must be considered for any therapeutical approach using anti-inflammatory treatment.

Matrix metalloproteinases (MMPs) are central to tissue remodelling; however, little is known about the temporal pattern and differential regulation of hepatic MMP expression in the course of chronic human liver disease. Using quantitative reverse transcription–PCR ELISA assays, we studied hepatic mRNA expression of MMP-1, -2, -3, -7, -9, -10, -11, -13 and -14 in patients with chronic hepatitis C and hepatitis C virus-induced end-stage liver cirrhosis and controls. Results were compared with histology, hepatic expression of tissue inhibitor of metalloproteinases (TIMP)-1, -2 and -3, procollagen types I and IV, laminin, and with circulating protein levels of hyaluronate, TIMP-1 and -2 and MMP proenzymes, as measured by ELISA. The impact of the MMP-3(-1171) promoter polymorphism on hepatic MMP-3 expression was analysed. Hepatic mRNA expression data identified differentially regulated groups of MMPs during the course of chronic hepatitis C, showing either steadily increasing mRNA expression with disease progression (MMP-1, -2, -7 and -14) or transiently elevated expression (MMP-9, -11 and -13). The first group closely correlated to the parameters of fibrogenesis. Hepatic MMP-3 expression was unrelated to disease stage, but was determined by the MMP-3(-1171) promoter polymorphism. In conclusion, MMP expression during the course of chronic hepatitis C appears to be a closely regulated process, with different clusters of coordinately regulated MMP genes being identified.

Ischemic stroke patients are prone to infection by stroke-induced immunodepression. We hypothesized that levels of lipopolysaccharide binding protein (LBP), interleukin-10 (IL-10), IL-6 and C-reactive protein (CRP) are early predictors for the development of stroke-associated infection. Fifty-six patients with ischemic stroke (n = 51) and transient ischemic attack (TIA) (n = 5) who presented within 6 hours after symptom onset and who were free of detectable infection on admission were included in the study. Of these, 20 developed early infections during the first week. Blood samples were taken at 6, 12, and 24 hours and at 3 and 7 days after stroke onset. Levels of LBP, Il-10, IL-6 and CRP, as well as S100B, were measured as markers of inflammation and brain damage by commercially available immunometric tests. In the univariate analysis, levels of LBP, IL-10, IL-6 and CRP significantly differed between patients who developed an infection and those who did not. In the binary logistic regression analysis, which was adjusted for National Institutes of Health Stroke Scale (NIHSS) on admission, stroke subtype and S100B peak levels, as indicator of the extent of brain damage, IL-10 at 6 hours, CRP at 6 hours and NIHSS on admission were identified as independent predictors of infection (IL-10: P = 0.009; CRP: P = 0.018; NIHSS: P = 0.041). The area under the curve (AUC) of the receiver operating characteristic (ROC) curves in relation to the dichotomized status of the infection (infection versus no infection) was 0.74 (95% confidence interval: 0.59 to 0.88) for CRP at 6 hours, 0.76 (0.61 to 0.9) for IL-10 at 6 hours, 0.83 (0.71 to 0.94) for NIHSS on admission and 0.94 (0.88 to 1) for the combination of CRP, IL-10 and NIHSS. In a subanalysis, 16 patients with early infections were matched with 16 patients without infection according to S100B peak levels. Here, the temporal pattern of LBP, IL-10, IL-6 and CRP significantly differed between the patient groups. Our data show that blood levels of inflammation markers may be used as early predictors of stroke-associated infection. We propose prospective studies to investigate if the calculated cut-offs of CRP, IL-10 and NIHSS might help to identify patients who should receive early preventive antibiotic treatment.