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.


Available from: Nils G Morgenthaler
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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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    ABSTRACT: Biomarkers are useful for establishing disease severity or prognosis in patients with chronic kidney disease. The aim of our study was to determine the plasma concentrations of novel cardiovascular biomarkers in patients on chronic hemodialysis in the context of published upper reference limits (URL) of these biomarkers; and to compare the plasma concentrations of those same analytes before and after hemodialysis session. Plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), mid-regional pro-A-type natriuretic peptide (MR-proANP), mid-regional pro-adrenomedullin (MR-proADM), C-terminal pro-endothelin-1 (CT-proET-1), C-terminal pro-arginine vasopressin (CT-proAVP, also known as Copeptin) and soluble ST2 (sST2) were measured in 28 patients before and after dialysis session. Of the 28 patients with conventional hemodialysis, 24 had low-flux hemofiltration and 4 had high-flux hemodiafiltration. Median plasma concentrations of the biomarkers obtained before hemodialysis were as follows: NT-proBNP, 11307ng/L (URL, 500ng/L); MR-proANP, 778 pmol/L (URL, 250 pmol/L); MR-proADM, 2.57nmol/L (URL, 0.52nmol/L); median CT-proET-1, 252 pmol/L (URL, 75 pmol/L); median CT-proAVP, 142 pmol/L (URL, 19 pmol/L); and median sST2, 27ng/mL (URL, 50ng/mL). Median relative analyte changes after low-flux vs. high-flux dialysis compared to predialysis values were +19% vs. -43% for NT-proBNP; +7% vs. -45% for MR-proANP; -2% vs. -63% for MR-proADM; -19% vs. -61% for CT-proET-1; +13% vs. -64% for CT-proAVP; and +2% vs. +3% for sST2. Plasma concentrations of the investigated biomarkers were markedly increased in chronic hemodialysis patients (with the exception of sST2). After hemodialysis session, analyte concentrations (with the exception of sST2) decreased significantly using a high-flux membrane but not if using a low-flux membrane. Copyright © 2015. Published by Elsevier Inc.
    Clinical biochemistry 07/2015; 48(16). DOI:10.1016/j.clinbiochem.2015.07.031 · 2.28 Impact Factor
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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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    ABSTRACT: Background The role of mixed pneumonia (virus + bacteria) in community-acquired pneumonia (CAP) has been described in recent years. However, it is not known whether the systemic inflammatory profile is different compared to monomicrobial CAP. We wanted to investigate this profile of mixed viral-bacterial infection and to compare it to monomicrobial bacterial or viral CAP. Methods We measured baseline serum procalcitonin (PCT), C reactive protein (CRP), and white blood cell (WBC) count in 171 patients with CAP with definite etiology admitted to a tertiary hospital: 59 (34.5%) bacterial, 66 (39.%) viral and 46 (27%) mixed (viral-bacterial). Results Serum PCT levels were higher in mixed and bacterial CAP compared to viral CAP. CRP levels were higher in mixed CAP compared to the other groups. CRP was independently associated with mixed CAP. CRP levels below 26 mg/dL were indicative of an etiology other than mixed in 83% of cases, but the positive predictive value was 45%. PCT levels over 2.10 ng/mL had a positive predictive value for bacterial-involved CAP versus viral CAP of 78%, but the negative predictive value was 48%. Conclusions Mixed CAP has a different inflammatory pattern compared to bacterial or viral CAP. High CRP levels may be useful for clinicians to suspect mixed CAP.
    BMC Pulmonary Medicine 07/2014; 14(1):123. DOI:10.1186/1471-2466-14-123 · 2.40 Impact Factor
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    • "Thus, there are restrictions with interpreting the ADM data of these studies due to the limited number of patients investigated and the type of ADM assays used, and consequently, the true potential clinical value of ADM measurement in septic patients has been difficult to judge. Measurement of a stable fragment of the ADM precursor peptide, namely MR-proADM, has been introduced to circumvent some of these existing problems [22-24]. However, conceptually, using MR-proADM as a surrogate for ADM has limitations: It does not reflect potential imbalances between the non-functional glycine-extended and the bioactive amidated ADM, and it must be assumed to have different clearing kinetics to ADM. "
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    ABSTRACT: The incidence of death among patients admitted for severe sepsis or septic shock is high. Adrenomedullin (ADM) plays a central role in initiating the hyperdynamic response during the early stages of sepsis. Pilot studies indicate an association of plasma ADM with the severity of the disease. In the present study we utilized a novel sandwich immunoassay of bioactive plasma ADM in patients hospitalized with sepsis in order to assess the clinical utility. We enrolled 101 consecutive patients admitted to the emergency department with suspected sepsis in this study. Sepsis was defined by fulfillment of at least two systemic inflammatory response syndrome (SIRS) criteria plus clinical suspicion of infection. Plasma samples for ADM measurement were obtained on admission and for the next four days. The 28-day mortality rate was recorded. ADM at admission was associated with severity of disease (correlation with Acute Physiology and Chronic Health Evaluation II (APACHE II) score: r = 0.46; P <0.0001). ADM was also associated with 28-day mortality (ADM median (IQR): survivors: 50 (31 to 77) pg/mL; non-survivors: 84 (48 to 232) pg/mL; P <0.001) and was independent from and additive to APACHE II (P = 0.02). Cox regression analysis revealed an additive value of serial measurement of ADM over baseline assessment for prediction of 28-day mortality (P < 0.01). ADM was negatively correlated with mean arterial pressure (r = -0.39; P <0.0001), and it strongly discriminated those patients requiring vasopressor therapy from the others (ADM median (IQR): no vasopressors 48 (32 to 75) pg/mL; with vasopressors 129 (83 to 264) pg/mL, P <0.0001). In patients admitted with sepsis, severe sepsis or septic shock plasma ADM is strongly associated with severity of disease, vasopressor requirement and 28-day mortality.
    Critical care (London, England) 02/2014; 18(1):R34. DOI:10.1186/cc13731 · 4.48 Impact Factor
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