Thaha M, Pranawa W, Yogiantoro M, Tomino Y
Division of Nephrology-Hypertension, Department of Internal Medicine, Airlangga University School of Medicine, Surabaya, Indonesia.
Clin Nephrol. 2008 Jan;69(1):24-32. doi: 10.5414/cnp69024.
Cardiovascular disease is the main cause of mortality in chronic kidney disease patients. Moreover, uremic patients are in a pro-oxidant state and show an increase in asymmetric dimethylarginine (ADMA) levels due to inhibition of the enzyme dimethylarginine dimethylaminohydrolase (DDAH). Asymmetric dimethylarginine per se seems responsible for a 52% increase in the risk of death and for a 34% increase in the risk of cardiovascular events in dialysis patients. N-acetylcysteine (NAC) is a thiol molecule that has direct and indirect antioxidant effects which decrease reactive oxidant species and increase the bioavailability of the DDAH enzyme. The aim of the current study was to determine the effect of intravenous NAC on plasma ADMA level when administered during hemodialysis in end-stage renal disease (ESRD) patients.
40 patients with ESRD were randomized to receive a 4-hour intravenous infusion of NAC or placebo during a 4-hour hemodialysis session. There were 3 diabetic patients (15%) in the treatment group and 6 patients in the control group. Plasma ADMA levels were measured before and immediately after hemodialysis. Hemodynamic parameters, including pulse pressure, were also measured. The paired t-test was used to compare the difference of ADMA levels before and after hemodialysis in each group, while the independent t-test was used to compare the difference of ADMA levels between the groups.
Compared with the pre-dialysis condition, there was a decrease of ADMA level in the control group (1.1253 +/- 0.1797 microM to 0.8676 +/- 0.1449 microM) (p < 0.001), and in the NAC group (1.1522 +/- 0.1737 microM to 0.7844 +/- 0.1586 microM) (p < 0.001). Compared with hemodialysis alone, NAC had a greater lowering effect on the ADMA level (21.3 vs. 31.9%, p < 0.05).
N-acetylcysteine (NAC) administered intravenously during hemodialysis reduced asymmetric dimethylarginine (ADMA) levels more significantly than hemodialysis alone.
心血管疾病是慢性肾脏病患者死亡的主要原因。此外，尿毒症患者处于促氧化状态，由于二甲基精氨酸二甲胺水解酶（DDAH）受抑制，其不对称二甲基精氨酸（ADMA）水平升高。不对称二甲基精氨酸本身似乎导致透析患者死亡风险增加52%，心血管事件风险增加34%。N-乙酰半胱氨酸（NAC）是一种硫醇分子，具有直接和间接抗氧化作用，可减少活性氧化物质并提高DDAH酶的生物利用度。本研究的目的是确定终末期肾病（ESRD）患者在血液透析期间静脉注射NAC对血浆ADMA水平的影响。
40例ESRD患者在4小时血液透析期间随机接受4小时静脉输注NAC或安慰剂。治疗组有3例糖尿病患者（15%），对照组有6例。在血液透析前和透析结束后立即测量血浆ADMA水平。还测量了包括脉压在内的血流动力学参数。配对t检验用于比较每组血液透析前后ADMA水平的差异，独立t检验用于比较两组之间ADMA水平的差异。
与透析前相比，对照组ADMA水平降低（从1.1253±0.1797微摩尔/升降至0.8676±0.1449微摩尔/升）（p<0.001），NAC组也降低（从1.1522±0.1737微摩尔/升降至0.7844±0.1586微摩尔/升）（p<0.001）。与单纯血液透析相比，NAC对ADMA水平的降低作用更大（21.3%对31.9%，p<0.05）。
血液透析期间静脉注射N-乙酰半胱氨酸（NAC）比单纯血液透析更显著地降低不对称二甲基精氨酸（ADMA）水平。
