Measurement of midregional proadrenomedullin in plasma with an immunoluminometric assay.
BACKGROUND
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.


METHODS
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.


RESULTS
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].


CONCLUSIONS
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.
Morgenthaler
Nils G
NG
Research Department, B.R.A.H.M.S AG, Biotechnology Centre Hennigsdorf/Berlin, Germany. n.morgenthaler@brahms.de
Struck
Joachim
J
Alonso
Christine
C
Bergmann
Andreas
A
D000293:Adolescent; D053607:Adrenomedullin; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D002318:Cardiovascular Diseases / Q000097:blood*; D005260:Female; D006801:Humans; D007118:Immunoassay / Q000379:methods; D008163:Luminescent Measurements / Q000379:methods*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011498:Protein Precursors / Q000097:blood*; D011506:Proteins; D012680:Sensitivity and Specificity; D018805:Sepsis / Q000097:blood*; D013696:Temperature; D013997:Time Factors
D011498:Protein Precursors; D011506:Proteins; C088633:proadrenomedullin; D053607:Adrenomedullin