title: Relationship of asymmetric dimethylarginine to dialysis treatment and atherosclerotic disease.
abstract: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of endothelial nitric oxide (NO) synthase. Its concentration is elevated in patients with end-stage renal disease (ESRD), in part because it is excreted via the kidneys. In addition, ADMA is degraded by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), which hydrolyzes ADMA to L-citrulline and dimethylamine. Activity of DDAH is decreased by oxidized low density lipoprotein (LDL) or tumor necrosis factor-alpha (TNF-alpha) in vitro yielding increased levels of ADMA. Furthermore, plasma levels of ADMA are elevated in hyperhomocyst(e)inemia and in hypertensive patients on a high salt diet. Data from several experimental studies suggest that ADMA concentrations in a pathophysiologically high range (3 to 10 micromol/L) significantly inhibit vascular NO formation by NO synthase in the presence of L-arginine in isolated human blood vessels, cultured macrophages, and in cultured endothelial cells. It has been well demonstrated that ADMA accumulates in chronic renal failure. Although there is controversy concerning the absolute concentration of ADMA, all authors found a two- to sixfold increase in ADMA levels in patients in chronic renal failure as compared to controls. Different dialysis treatment strategies differentially affect ADMA levels. The presence of atherosclerosis is associated with higher ADMA levels in patients with normal renal function as well as in dialysis patients, but this phenomenon may be unrelated to renal handling of ADMA. Reduced NO elaboration secondary to accumulation of ADMA may be an important pathogenic factor for atherosclerosis in chronic renal failure and ADMA may be a new uremic toxin. Clinical studies on the effect of ADMA are needed to further elucidate its pathophysiological role in atherosclerosis and uremia.
authors.affiliation: Institute of Clinical Pharmacology and Department of Nephrology, Hannover Medical School, 30625 Hannover, Germany. Kielstein@yahoo.com
authors.forename: J T
authors.initials: JT
authors.lastname: Kielstein
authors.forename: S M
authors.initials: SM
authors.lastname: Bode-Böger
authors.forename: J C
authors.initials: JC
authors.lastname: Frölich
authors.forename: H
authors.initials: H
authors.lastname: Haller
authors.forename: R H
authors.initials: RH
authors.lastname: Böger
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives / Q000378:metabolism*; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism*; D015415:Biomarkers; D006801:Humans; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000378:metabolism / Q000628:therapy; D009569:Nitric Oxide / Q000096:biosynthesis; D010530:Peritoneal Dialysis; D006435:Renal Dialysis; D014511:Uremia / Q000378:metabolism
chemical_list: D015415:Biomarkers; D009569:Nitric Oxide; C018524:N,N-dimethylarginine; D001120:Arginine