Impact of vitamin E on plasma asymmetric dimethylarginine (ADMA) in chronic kidney disease (CKD): a pilot study.
BACKGROUND
Asymmetric dimethylarginine (ADMA), an endogenous inhibitor of endothelial nitric oxide synthase and a proposed cardiovascular risk factor, is elevated in chronic kidney disease (CKD). Pharmacological strategies that lower plasma concentration of ADMA may be expected to increase nitric oxide (NO.) bioavailability and potentially limit atherosclerosis. We hypothesized that the antioxidant alpha-tocopherol (vitamin E) reduces ADMA levels in CKD.


METHODS
An open-label pilot interventional study using 800 IU of vitamin E was undertaken in eight stable out-patients with non-diabetic CKD (creatinine clearance <30 ml/min/1.73 m(2)) and six healthy controls, with the objective of measuring plasma ADMA levels at baseline and after 8 weeks of treatment. Plasma ADMA, symmetric dimethylarginine (SDMA) and alpha-tocopherol concentrations were determined at study entry and exit using high-performance liquid chromatography, while plasma total F2-isoprostanes, an index of oxidative stress, were measured using a commercially available enzyme-linked immunosorbent assay kit.


RESULTS
ADMA and SDMA concentrations were significantly higher in the plasma of patients compared with that of controls (P </= 0.001). After treatment with vitamin E, ADMA decreased by 23% in six of eight patients (P <0.001). The remaining two patients showed either an increase or no change (overall, P = 0.16). There was no significant change in plasma F2-isoprostanes with vitamin E treatment for 8 weeks.


CONCLUSIONS
Antioxidant therapy with vitamin E has the potential to lower ADMA levels in CKD patients, implying increased NO. availability. This strategy merits further exploration in the setting of CKD prior to renal replacement.
Saran
Rajiv
R
Division of Nephrology, University of Michigan, Ann Arbor, MI 48103-4262, USA. rsaran@umich.edu
Novak
James E
JE
Desai
Anjali
A
Abdulhayoglu
Emil
E
Warren
Jeffrey S
JS
Bustami
Rami
R
Handelman
Garry J
GJ
Barbato
Damian
D
Weitzel
William
W
D'Alecy
Louis G
LG
Rajagopalan
Sanjay
S
D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood*; D002908:Chronic Disease; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007674:Kidney Diseases / Q000097:blood*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000187:drug effects*; D010865:Pilot Projects; D024502:alpha-Tocopherol / Q000494:pharmacology*
D000975:Antioxidants; C018524:N,N-dimethylarginine; D001120:Arginine; D024502:alpha-Tocopherol