In their letter, Kurtoglu et al 1 suggest an association of renal dysfunction and asymmetric dimethylarginine (ADMA) levels in patients with acute ischemic stroke because an association has been demonstrated in other cardiovascular diseases. Using the Spearman rank correlation, we found as well a significant negative correlation between the glomerular filtration rate and ADMA serum levels in our current study (glomerular filtration rate on admission versus ADMA day 1: r=−0. 770, P<0.001; day 2: r=−0.783, P<0.001; day 3: r=−0.819, P<0.001; day 4: r=−0.765, P<0.001; day 7: r=−0.714, P<0.001).2 However, in another recent study in patients with acute stroke, ADMA levels were correlated neither with creatinine levels nor with the glomerular filtration rate.3 The large variety from absent to mostly poor but at times good relationship between ADMA and renal function had been summarized before. 4 Because only ≈20% of ADMA is excreted in the urine, >80% of ADMA is metabolized by dimethylarginine dimethylaminohydrolases in the liver and to some degree in the kidney, and also by alanine-glyoxylate aminotransferase 2 in the kidney or via acetylation in the liver. Therefore, it is conceivable that, depending on the reason for renal impairment, the decline in renal excretory function is paralleled by a reduction in dimethylarginine dimethylaminohydrolases activity (in the kidney). This might serve as an explanation why ADMA is related to parameters of renal function in some of the studies. Whether the different findings could also depend on the distribution of patients according to stroke subtypes remains unclear because stroke subtypes were only indicated in our study. Importantly, in our current study, the treatment effect on ADMA levels in the recombinant tissue-type plasminogen activator+placebo group remained after additional adjustment for glomerular filtration rate in the repeated measures analysis (P<0.05). In this group, ADMA levels were significantly decreased compared with the placebo group.
2Kurtoglu et al 1 also emphasized the importance of statin treatment for ADMA levels in ischemic stroke. Nishiyama et al 5 observed a significant decrease in ADMA levels in 56 patients who were treated with statins for the first time during a period of 90 days beginning ≥3 months after ischemic stroke. In a subanalysis of our current study, in patients who were pretreated with statins or in whom treatment was initiated within the first week after the event (n=29), ADMA levels (day 1 to day 7) were not different compared with the nonstatin-treated patients (n=61; Mann-Whitney U test, P>0.05). This might be because of the fact that Nishiyama et al 5 included patients in the chronic stage ≥3 months after stroke, whereas our study investigated patients with hyperacute stroke. Therefore, in our study, dynamics in ADMA levels, which take place within the first days after the event of stroke, might overlap with any effects from pretreatment with statins.2 Finally, further studies are warranted to clarify the role of ADMA levels in p...