Asymmetric dimethylarginine, C-reactive protein, and carotid intima-media thickness in end-stage renal disease.
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase that has been linked to endothelial dysfunction and atherosclerosis in the general population. ADMA is also elevated in end-stage renal disease and may contribute to the high cardiovascular risk in patients with chronic renal failure. A prospective cohort study was performed to investigate the relationship between plasma ADMA, C-reactive protein (CRP), and intima-media thickness (IMT) in 90 patients undergoing hemodialysis. In the baseline study, plasma ADMA was directly related to IMT both on univariate analysis (r = 0.32, P = 0.002) and on multiple regression analysis (beta = 0.23, P = 0.01). In the follow-up study (15 mo) IMT changes were significantly related to ADMA (r = 0.51, P = 0.02) and serum CRP (r = 0.53, P = 0.01) in patients with initially normal IMT. In these patients, ADMA and CRP were strongly interrelated (r = 0.64, P = 0.002), and on multiple regression analysis the interaction between ADMA and CRP emerged as the sole independent predictor of the progression of intimal lesions. Independently of other risk factors, plasma ADMA in patients on hemodialysis is significantly related to IMT. Furthermore, in patients with initially normal IMT, ADMA and CRP are interacting factors in the progression of carotid intimal lesions. These data support the hypothesis that accumulation of this endogenous inhibitor of NO synthase is an important risk factor for cardiovascular disease in chronic renal failure and suggest a possible link between ADMA and inflammation.
Zoccali
Carmine
C
*CNR Centre of Clinical Physiology and Renal Unit and Division of Cardiology, Morelli Hospital, Reggio, Calabria, Italy; Clinical Pharmacology Unit, Department of Pharmacology, University Hospital Hamburg-Eppendorf, Germany; Department of Internal Medicine, Catania University, Catania, Italy.
Benedetto
Francesco Antonio
FA
*CNR Centre of Clinical Physiology and Renal Unit and Division of Cardiology, Morelli Hospital, Reggio, Calabria, Italy; Clinical Pharmacology Unit, Department of Pharmacology, University Hospital Hamburg-Eppendorf, Germany; Department of Internal Medicine, Catania University, Catania, Italy.
Maas
Renke
R
*CNR Centre of Clinical Physiology and Renal Unit and Division of Cardiology, Morelli Hospital, Reggio, Calabria, Italy; Clinical Pharmacology Unit, Department of Pharmacology, University Hospital Hamburg-Eppendorf, Germany; Department of Internal Medicine, Catania University, Catania, Italy.
Mallamaci
Francesca
F
*CNR Centre of Clinical Physiology and Renal Unit and Division of Cardiology, Morelli Hospital, Reggio, Calabria, Italy; Clinical Pharmacology Unit, Department of Pharmacology, University Hospital Hamburg-Eppendorf, Germany; Department of Internal Medicine, Catania University, Catania, Italy.
Tripepi
Giovanni
G
*CNR Centre of Clinical Physiology and Renal Unit and Division of Cardiology, Morelli Hospital, Reggio, Calabria, Italy; Clinical Pharmacology Unit, Department of Pharmacology, University Hospital Hamburg-Eppendorf, Germany; Department of Internal Medicine, Catania University, Catania, Italy.
Salvatore Malatino
Lorenzo
L
*CNR Centre of Clinical Physiology and Renal Unit and Division of Cardiology, Morelli Hospital, Reggio, Calabria, Italy; Clinical Pharmacology Unit, Department of Pharmacology, University Hospital Hamburg-Eppendorf, Germany; Department of Internal Medicine, Catania University, Catania, Italy.
Böger
Rainer
R
*CNR Centre of Clinical Physiology and Renal Unit and Division of Cardiology, Morelli Hospital, Reggio, Calabria, Italy; Clinical Pharmacology Unit, Department of Pharmacology, University Hospital Hamburg-Eppendorf, Germany; Department of Internal Medicine, Catania University, Catania, Italy.
D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism*; D002097:C-Reactive Protein / Q000378:metabolism*; D002339:Carotid Arteries / Q000000981:diagnostic imaging*; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007676:Kidney Failure, Chronic / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016037:Single-Blind Method; D017539:Tunica Intima / Q000000981:diagnostic imaging*; D017540:Tunica Media / Q000000981:diagnostic imaging*; D018615:Ultrasonography, Doppler, Color
C018524:N,N-dimethylarginine; D002097:C-Reactive Protein; D001120:Arginine