Asymmetric dimethyl-arginine (ADMA) response to inflammation in acute infections

• Published in: Nephrology, dialysis, transplantation Vol. 22; no. 3; pp. 801 - 806
• Main Authors: Zoccali, Carmine, Maas, Renke, Cutrupi, Sebastiano, Pizzini, Patrizia, Finocchiaro, Piero, Cambareri, Francesco, Panuccio, Vincenzo, Martorano, Carmela, Schulze, Friedrich, Enia, Giuseppe, Tripepi, Giovanni, Boger, Rainer
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.03.2007; Oxford Publishing Limited (England)
• Subjects: Acute Disease; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Arginine - analogs & derivatives; Arginine - blood; asymmetrical dimethyl-arginine; Bacterial Infections - blood; Bacterial Infections - physiopathology; Biological and medical sciences; Biomarkers - blood; Blood Pressure - physiology; C-reactive protein; C-Reactive Protein - metabolism; Calcitonin - blood; Calcitonin Gene-Related Peptide; Chromatography, High Pressure Liquid; Creatinine - blood; Disease Progression; Emergency and intensive care: renal failure. Dialysis management; Enzyme-Linked Immunosorbent Assay; Female; Follow-Up Studies; Glycoproteins; Human viral diseases; Humans; Infectious diseases; inflammation; Inflammation - blood; Intensive care medicine; interleukin-6; Interleukin-6 - blood; Male; Medical sciences; Middle Aged; Nephrology. Urinary tract diseases; Nephropathies. Renovascular diseases. Renal failure; Nitric Oxide Synthase - antagonists & inhibitors; Nitric Oxide Synthase - blood; procalcitonin; Protein Precursors - blood; Renal failure; Severity of Illness Index; Tyrosine - analogs & derivatives; Tyrosine - blood; Viral diseases; Viral hepatitis; procalcitonin; C-reactive protein; asymmetrical dimethyl-arginine; inflammation; interleukin-6; Kidney disease; Urinary system disease; Hemodialysis; Procalcitonin; Inflammation; Infection; Interleukin 6; Extrarenal dialysis; Arginine; Aminoacid; Renal failure; C reactive protein
• ISSN: 0931-0509; 1460-2385
• DOI: 10.1093/ndt/gfl719

Background and methods. The endogenous inhibitor of nitric oxide synthase (NOs) asymmetrical dimethyl-arginine (ADMA) has been implicated as a possible modulator of inducible NOs during acute inflammation. We examined the evolution in the plasma concentration of ADMA measured at the clinical outset of acute inflammation and after its resolution in a series of 17 patients with acute bacterial infections. Results. During the acute phase of inflammation/infection, patients displayed very high levels of C-reactive protein (CRP), interleukin-6 (IL-6), procalcitonin and nitrotyrosine. Simultaneous plasma ADMA concentration was similar to that in healthy subjects while symmetric dimethyl-arginine (SDMA) levels were substantially increased and directly related with creatinine. When infection resolved, ADMA rose from 0.62 ± 0.23 to 0.80 ± 0.18 μmol/l (+29%, P = 0.01) while SDMA remained unmodified. ADMA changes were independent on concomitant risk factor changes and inversely related with baseline systolic and diastolic pressure. Changes in the ADMA/SDMA ratio were compatible with the hypothesis that inflammatory cytokines activate ADMA degradation. Conclusions. Resolution of acute inflammation is characterized by an increase in the plasma concentration of ADMA. The results imply that ADMA suppression may actually serve to stimulate NO synthesis or that in this situation plasma ADMA levels may not reflect the inhibitory potential of this methylarginine at the cellular level.