Reference values for plasma concentrations of asymmetrical dimethylarginine (ADMA) and other arginine metabolites in men after validation of a chromatographic method.
BACKGROUND
Owing to the growing number of reports in the literature on ADMA as a possibly useful marker of endothelial health, its use in the clinical laboratory is of increasing interest. Age dependency and the small, but statistically significant differences between healthy subjects and disease groups are difficult to interpret. Additionally, levels of ADMA in comparable patient groups of different studies vary widely, even when similar methods have been used.


METHODS
After analytical evaluation of a chromatographic method according to international guidelines, we analysed asymmetrical (ADMA) and symmetrical dimethyl arginine (SDMA), homo-arginine and arginine in EDTA plasma of 292 healthy males aged 20 to 75 years (y) who had passed strict inclusion/exclusion criteria. For statistical analysis, 4 age groups were formed. Group differences were identified with the non-parametric Kruskal-Wallis test.


RESULTS
Calibration curves were linear throughout the selected ranges; the standard deviation for the regression line, recovery, imprecision, and accuracy results were all highly satisfactory. The reference ranges of ADMA for the 4 age groups are presented as age (mean+/-SD of age group, y); number of subjects; median, 2.5th-97.5th percentile: group <35 y: 26.7+/-4.0 y; n=78; 0.58, 0.43-0.69 micromol/L; group 35-49 y: 41.6+/-4.0 y; n=93; 0.59, 0.45-0.73 micromol/L; group 50-65 y: 57.5+/-4.2 y; n=82; 0.61, 0.46-0.78 micromol/L; and group >65 y: 69.6+/-3.3 y; n=39; 0.64, 0.54-0.79 micromol/L.


CONCLUSIONS
Only highly precise methods are able to detect small differences between groups. The application of an evaluated method to a well defined group of healthy subjects should provide a basis for comparison of ADMA concentrations in different patient populations of future studies.
Meinitzer
Andreas
A
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Austria. andreas.meinitzer@klinikum-graz.at
Puchinger
Markus
M
Winklhofer-Roob
Brigitte M
BM
Rock
Edmond
E
Ribalta
Josep
J
Roob
Johannes M
JM
Sundl
Isabella
I
Halwachs-Baumann
Gabriele
G
März
Winfried
W
D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood* / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006709:Homoarginine / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged
C487735:dimethylarginine; D006709:Homoarginine; C024917:symmetric dimethylarginine; D001120:Arginine