title: Net renal extraction of asymmetrical (ADMA) and symmetrical (SDMA) dimethylarginine in fasting humans.
abstract: BACKGROUND
  Recently, the potential importance of dimethylarginines as endogenously produced inhibitors of nitric oxide synthase has become clearer. Interestingly, elevated levels have been reported in patients with vascular disease, but especially in patients suffering end-stage renal disease. Although the kidney obviously seems to play a key role in the elimination of dimethylarginines, clear insight into the renal handling of these compounds is lacking. Thus, our aim was to investigate the renal extraction of dimethylarginines.
  
  
  METHODS
  Plasma concentrations of dimethylarginines were determined in both arterial and renal venous blood in 20 fasting patients with normal renal function. Renal extraction was calculated as the arteriovenous concentration difference divided by the arterial concentration times 100%.
  
  
  RESULTS
  A significant renal extraction was found for both dimethylarginines. Renal extraction was significantly higher for asymmetrical dimethylarginine (ADMA) when compared with symmetrical dimethylarginine (SDMA) (16.2 vs 10.5% respectively, P=0.001). In addition, arterial SDMA concentration, but not ADMA concentration, significantly correlated with arterial creatinine concentration.
  
  
  CONCLUSIONS
  In healthy humans, the kidney contributes to the regulation of plasma levels of dimethylarginines, since both ADMA and SDMA were significantly extracted from the arterial supply. Interestingly, a higher renal extraction of ADMA was found when compared to SDMA extraction, which strongly suggests the presence of an additional catabolic pathway for ADMA in the kidney.
authors.affiliation: Department of Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Nijveldt
authors.forename: Paul A M
authors.initials: PA
authors.lastname: Van Leeuwen
authors.forename: Coen
authors.initials: C
authors.lastname: Van Guldener
authors.forename: Coen D A
authors.initials: CD
authors.lastname: Stehouwer
authors.forename: Jan A
authors.initials: JA
authors.lastname: Rauwerda
authors.forename: Tom
authors.initials: T
authors.lastname: Teerlink
mesh_terms: D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood / Q000737:chemistry / Q000378:metabolism*; D001158:Arteries; D003404:Creatinine / Q000097:blood / Q000378:metabolism; D005215:Fasting / Q000378:metabolism*; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008968:Molecular Conformation; D009994:Osmolar Concentration
chemical_list: C018524:N,N-dimethylarginine; D001120:Arginine; D003404:Creatinine