Effect of simvastatin on plasma asymmetric dimethylarginine concentration in patients with chronic kidney disease.
BACKGROUND
The endogenous inhibitor of nitric oxide (NO) synthase, asymmetric dimethylarginine (ADMA), is a strong cardiovascular (CV) risk marker in patients with chronic renal insufficiency. Statins have pleiotropic effects and are currently considered as potential ADMA-lowering agents.


METHODS
We investigated the effect of simvastatin on plasma ADMA levels in 35 patients with chronic kidney disease (CKD) by performing a secondary analysis of a randomized double-blind placebo-controlled trial where patients were randomized to receive simvastatin or placebo for 6 months.


RESULTS
Plasma ADMA was higher in CKD patients (0.84 +/- 0.14 micromol/L) than in healthy subjects (0.69 +/- 0.10 micromol/L) (p<0.001). In CKD patients, ADMA at baseline was related directly with triglycerides (r=0.42, p=0.01) and inversely with HDL cholesterol (r=-0.37, p=0.03) and creatinine clearance (p=0.03). As expected, simvastatin caused significant reductions in total cholesterol, LDL cholesterol and triglycerides, as well as in C-reactive protein (CRP; -28%, p=0.001) and IL-6 (-20%, p=0.05) but failed to decrease plasma ADMA both in crude and adjusted analyses.


CONCLUSIONS
Simvastatin does not modify plasma ADMA. Because raised ADMA is known to prevent the favorable effect of statins on myocardial blood flow, cointerventions aimed at lowering or antagonizing ADMA may either prompt or potentiate the cardiovascular protective effect of simvastatin.
Panichi
Vincenzo
V
Nephrology Section, Department of Internal Medicine, University of Pisa, Pisa, Italy.
Mantuano
Emanuela
E
Paoletti
Sabrina
S
Santi
Samuele
S
Manca Rizza
Giovanni
G
Cutrupi
Sebastiano
S
Pizzini
Patrizia
P
Spoto
Belinda
B
Tripepi
Giovanni
G
Zoccali
Carmine
C
D000328:Adult; D000368:Aged; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D002908:Chronic Disease; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007674:Kidney Diseases / Q000097:blood*; D008297:Male; D008875:Middle Aged; D019821:Simvastatin / Q000494:pharmacology*
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C018524:N,N-dimethylarginine; D001120:Arginine; D019821:Simvastatin