Article

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: 7.77). 10/2005; 51(10):1823-9. DOI: 10.1373/clinchem.2005.051110
Source: PubMed

ABSTRACT 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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    • "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 · 2.49 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
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    • "Elevated levels of ET-1 were found during systemic infections [16] and ET-1 levels correlated with mortality risk [21]. Recently, assays have become available to determine circulating mid-regional pro-adrenomedullin (MR-proADM) and carboxy-terminal pro-endothelin-1 (CT-proET-1) concentrations [26,27]. These peptides are co-synthesized with ADM and ET-1, respectively, and have the advantage of a longer half-life, lack of bioactivity and lack of protein binding, which makes them more suitable for daily practice [28]. "
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    ABSTRACT: We tested the hypothesis that higher mid-regional pro-adrenomedullin (MR-proADM), carboxy-terminal pro-endothelin-1 (CT-proET-1), procalcitonin (PCT) and C-reactive protein (CRP) plasma concentrations would be associated with increased prediction of mortality risk scores. Prospective observational study in two pediatric intensive care units (PICUs). 238 patients were included. MR-proADM, CT-proET-1, PCT and CRP levels were compared between children with PRISM III and PIM 2 > p75 (Group A; n = 33) and the rest (Group B; n = 205). Median (range) MR-proADM levels were 1.39 nmol/L (0.52--12.67) in group A vs. 0.54 (0.15--3.85) in group B (p < 0.001). CT-proET-1 levels were 172 pmol/L (27--500) vs. 58 (4--447) (p < 0.001). PCT levels were 7.77 ng/mL (0.34--552.00) vs. 0.28 (0.02--107.00) (p < 0.001). CRP levels were 6.23 mg/dL (0.08-28.25) vs. 1.30 mg/dL (0.00-42.09) (p = 0.210). The area under the ROC curve (AUC) for the differentiation of group A and B was 0.87 (95%CI:0.81--0.821) for MR-proADM, 0.86 (95%CI:0.79--0.92) for CT-proET-1 and 0.84 (95%CI:0.74--0.94) for PCT. A MR-proADM > 0.79 nmol/L had 93% sensitivity and 76% specificity to differentiate groups, whereas a CT-proET-1 > 123 pmol/L had 77% sensitivity and 84% specificity, and a PCT concentration > 2.05 ng/mL had 80% sensitivity and specificity. In critically ill children, high levels of MR-proADM, CT-proET-1 and PCT were associated with increased prediction of mortality risk scores. MR-proADM, CT-proET-1 and PCT concentrations higher than 0.80 nmol/L, 123 pmol/L and 2 ng/mL, respectively, could be used by clinicians to identify critically ill children at higher prediction of risk death scores.
    Critical care (London, England) 10/2013; 17(5):R240. DOI:10.1186/cc13064
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