Plasma Glial Fibrillary Acidic Protein in the Differential Diagnosis of Intracerebral Hemorrhage.

BACKGROUND AND PURPOSE: Plasma GFAP (glial fibrillary acidic protein) has recently emerged as a potential biomarker for the differentiation of acute intracerebral hemorrhage (ICH) from acute ischemic stroke (AIS). We prospectively assessed the diagnostic accuracy of GFAP in the differential diagnosis of ICH. METHODS: Consecutive patients presenting to the emergency department within 6 hours from symptom onset were evaluated. All patients underwent extensive diagnostic work-up and were classified according to discharge diagnosis in AIS, ICH, subarachnoid hemorrhage, and stroke mimics. GFAP was also measured in healthy volunteers (controls). Baseline stroke severity was evaluated using National Institutes of Health Stroke Scale. Receiver operating characteristic curve analysis was used to identify the optimal cutoff point for the differentiation between subgroups. Correlation analyses of GFAP plasma concentrations with baseline National Institutes of Health Stroke Scale and onset to sampling time were performed with the nonparametric Spearman rank test and fractional polynomial regression, respectively. RESULTS: Our study population consisted of 270 individuals (AIS: 121, ICH: 34, stroke mimics: 31, subarachnoid hemorrhage: 5, controls: 79). No differences on baseline stroke severity and onset to sampling time were detected between AIS and ICH. Higher median plasma GFAP values were documented in ICH compared with AIS, stroke mimics, and controls (P<0.001). Receiver operating characteristic analysis highlighted a cutoff value of 0.43 ng/mL as the optimal threshold for the differentiation between ICH and AIS (sensitivity: 91%, specificity: 97%). No association was detected between plasma GFAP concentrations and baseline stroke severity for both AIS (P=0.515) and ICH (P=0.387). In the fractional polynomial analysis, the association between GFAP concentration and onset to sampling time was best described by a J-shaped curve for AIS and an inverted U-shaped curve for ICH, with a peak at 2 hours. CONCLUSIONS: Plasma GFAP seems to be a sensitive and specific biomarker for the differentiation of ICH from both AIS and other acute neurological disorders, with the optimal diagnostic yield being present in the second hour from symptom onset.

Evaluation of a particle enhanced turbidimetric assay for the measurement of neutrophil gelatinase-associated lipocalin in plasma and urine on Architect-8000: Analytical performance and establishment of reference values.

OBJECTIVES: Neutrophil gelatinase-associated lipocalin (NGAL) is a promising biomarker for acute kidney injury. NGAL can be measured in both blood and urine. Apart from kidney injury, NGAL levels in both plasma and urine can be influenced by various pathological situations. Accurate evaluation and comparison of results deriving from clinical studies require robust assays, appropriate specimen handling and reference intervals that will reflect its levels in a healthy population for both biological matrices. METHODS: We report the analytical validation of a latex particle-enhanced turbidimetric immunoassay (PETIA) aimed to measure NGAL in plasma and urine on an automated biochemistry analyzer (ABBOTT-Architect-8000). Assay performance characteristics were evaluated using standard protocols. Urine and plasma specimen storage requirements were determined and reference ranges for blood and urine were determined using healthy controls. RESULTS: The assay is precise (total CV%<4.8%), and sensitive (limit of quantification: 8.4 ng/mL for plasma and 9.0 ng/mL for urine), showing no hook effect. Calibration is stable for at least 30 days. The assay showed excellent linearity over the studied interval (20-4450 ng/mL). The analyte is stable at 4 °C for at least 5 days, and at 20 °C for 4h. Gender specific reference ranges for plasma (male: 38.7-157.6 ng/mL, female: 24.4-142.5 ng/mL) and unisex for urine (<9.0-49.41 ng/mL) are proposed. CONCLUSION: Our data indicate that NGAL can be measured with adequate precision and sensitivity on automated biochemistry analyzers and its measurement could easily be added to a standard panel to screen kidney diseases.