Measurement of midregional proadrenomedullin in plasma with an immunoluminometric assay

Research Department, B.R.A.H.M.S AG, Biotechnology Centre Hennigsdorf/Berlin, Germany.
Clinical Chemistry (Impact Factor: 7.91). 10/2005; 51(10):1823-9. DOI: 10.1373/clinchem.2005.051110
Source: PubMed


Adrenomedullin (ADM) is a potent vasodilatory peptide, and circulating concentrations have been described for several disease states, including dysfunction of the cardiovascular system and sepsis. Reliable quantification has been hampered by the short half-life, the existence of a binding protein, and physical properties. Here we report the technical evaluation of an assay for midregional pro-ADM (MR-proADM) that does not have these problems.
MR-proADM was measured in a sandwich immunoluminometric assay using 2 polyclonal antibodies to amino acids 45-92 of proADM. The reference interval was defined in EDTA plasma of 264 healthy individuals (117 male, 147 female), and increased MR-proADM concentrations were found in 95 patients with sepsis and 54 patients with cardiovascular disease.
The assay has an analytical detection limit of 0.08 nmol/L, and the interassay CV was <20% for values >0.12 nmol/L. The assay was linear on dilution with undisturbed recovery of the analyte. EDTA-, heparin-, and citrate-plasma samples were stable (<20% loss of analyte) for at least 3 days at room temperature, 14 days at 4 degrees C, and 1 year at -20 degrees C. MR-proADM values followed a gaussian distribution in healthy individuals with a mean (SD) of 0.33 (0.07) nmol/L (range, 0.10-0.64 nmol/L), without significant difference between males or females. The correlation coefficient for MR-proADM vs age was 0.50 (P < 0.001). MR-proADM was significantly (P < 0.001) increased in patients with cardiovascular disease [median (range), 0.56 (0.08-3.9) nmol/L] and patients with sepsis [3.7 (0.72-25.4) nmol/L].
MR-proADM is stable in plasma of healthy individuals and patients. MR-proADM measurements may be useful for evaluating patients with sepsis, systemic inflammation, or heart failure.

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Available from: Nils G Morgenthaler
    • "Finally, tubes were washed four times with 1 ml of washing solution, and bound chemiluminescence was measured spectroscopically in a luminometer . According to the literature, the lower detection limit of the assay is 0.08 nmol/l, and the functional assay sensitivity defined as the lowest concentration detectable is less than 0.2 nmol/l with an inter-assay coefficient of variation of 20% (Morgenthaler et al., 2005). "
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    ABSTRACT: It has been postulated that patients with heart failure have a high risk of ventricular arrhythmias and sudden cardiac death resulting from anxiety-induced autonomic arousal. In the prospective and multicenter DIAST-CHF (Diagnostic Trial on Prevalence and Clinical Course of Diastolic Dysfunction and Heart Failure) study, we therefore, tested the hypothesis that adrenomedullin (ADM), a well-established predictor for cardiovascular outcome, is associated with self-rated anxiety symptoms in patients at risk of suffering from or actually with overt heart failure. Study participants with risk factors for diastolic dysfunction were requested to complete the Hospital Anxiety and Depression Scale (HADS), and plasma mid-regional pro-adrenomedullin (MR-proADM) concentrations were measured. In bivariate analysis, we found significantly lower plasma MR-proADM levels in patients with elevated HADS-anxiety scores above the clinically relevant cut-off level of ≥11 (n=118, 536pmol/l, interquartile range [IQR] 449-626) as compared to non-anxious study participants (n=1,292, 573pmol/l, IQR 486-702, p=0.001). A set of multivariate models adjusted for potential confounders confirmed the negative association between self-rated anxiety symptoms and plasma MR-proADM. In similar models, no significant association was detected between HADS-depression scores and MR-proADM. The inverse relationship between plasma MR-proADM and anxiety observed in patients with cardiovascular risk factors supports a previous experimental study using a mutant mouse line with a brain-specific loss of ADM expression which displayed hyperactive and over-anxious behavior. Further experimental and clinical studies are warranted to test the hypothesis that also in humans ADM acts as a neuromodulator with anxiolytic properties. Copyright © 2015. Published by Elsevier Ltd.
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    • "Median concentrations of MR-proANP are considered to be b45 pmol/L in healthy individuals and the URL is b 250 pmol/L [4] [5]. A reference value study on healthy blood donors and a population-based cohort revealed a median MR-proADM concentration b 0.45 nmol/L and an URL of ~ 0.52 nmol/L [6] [7]. The information given in the package insert and a published study on blood donors [8] refer to a median CT-proET-1 plasma concentration b 47 pmol/L in healthy individuals and an URL b 75 pmol/L. "
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    • "The assay has an analytical detection limit of 0.06 mg/L and a functional assay sensitivity of 0.11 mg/L. Procalcitonin concentrations were determined using sandwich immunoassays and time-resolved amplified cryptate emission (TRACE) measurement (PCT sensitive KRYPTOR, BRAHMS, Hennigsdorf, Germany), as described in detail previously [20]. The analytical detection limit and the functional assay sensitivity for the assays were 0.02 ng/mL and 0.06 ng/mL, respectively, for procalcitonin. "
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