title: Low dialysance of asymmetric dimethylarginine (ADMA)--in vivo and in vitro evidence of significant protein binding.
abstract: BACKGROUND
  Increased blood levels of the endogenous nitric oxide synthase inhibitor asymmetric dimethylarginine (ADMA) predict cardiovascular mortality in patients with end-stage renal disease. Despite its low molecular weight, available information on the impact of hemodialysis (HD) on ADMA plasma levels is controversial.
  
  
  METHODS
  We assessed plasma concentrations, dialyzer clearance and total amount of ADMA removed in 30 patients with end-stage renal disease during regular HD. In addition, plasma ADMA levels were assessed in 10 patients with acute renal failure treated with extended HD.
  
  
  RESULTS
  Regular HD decreased plasma creatinine (from 774 +/- 42 to 312 +/- 17 micromol/l) and urea (from 24.5 +/- 1.5 to 8.4 +/- 0.5 mmol/l) concentrations significantly (both p < 0.001), whereas plasma ADMA remained unchanged (4.35 +/- 0.19 vs. 4.76 +/- 0.24 micromol/l). ADMA clearance was 92 +/- 6 ml/min, and the total amount removed in the spent dialysate was 37 +/- 4 micromol. The clearances of creatinine (161 +/- 3 ml/min) and of urea (173 +/- 3 ml/min) were significantly higher. Furthermore, even during extended HD, plasma ADMA concentrations did not decrease significantly (1.73 +/- 0.22 vs. 1.63 +/- 0.18 micromol/l).
  
  
  CONCLUSIONS
  In conclusion, dialysance of ADMA is markedly lower than expected from its molecular weight because of significant protein binding of the substance. Since markedly increased ADMA blood concentrations have been linked to cardiovascular complications due to atherosclerosis in patients with ESRD, new strategies should be evaluated to remove this putative uremic toxin.
authors.affiliation: Division of Nephrology, Hannover Medical School, Hannover, Germany. Kielstein@yahoo.com
authors.forename: J T
authors.initials: JT
authors.lastname: Kielstein
authors.forename: R H
authors.initials: RH
authors.lastname: Böger
authors.forename: S M
authors.initials: SM
authors.lastname: Bode-Böger
authors.forename: J
authors.initials: J
authors.lastname: Martens-Lobenhoffer
authors.forename: G
authors.initials: G
authors.lastname: Lonnemann
authors.forename: J C
authors.initials: JC
authors.lastname: Frölich
authors.forename: H
authors.initials: H
authors.lastname: Haller
authors.forename: D
authors.initials: D
authors.lastname: Fliser
mesh_terms: D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D002318:Cardiovascular Diseases / Q000097:blood* / Q000517:prevention & control; D003401:Creatine / Q000097:blood; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007676:Kidney Failure, Chronic / Q000097:blood*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D006435:Renal Dialysis; D014508:Urea / Q000097:blood
chemical_list: C487735:dimethylarginine; D014508:Urea; D001120:Arginine; D003401:Creatine