血液透析患者血清不对称和对称二甲基精氨酸与发病率及死亡率
Serum Asymmetric and Symmetric Dimethylarginine and Morbidity and Mortality in Hemodialysis Patients.
作者信息
Shafi Tariq, Hostetter Thomas H, Meyer Timothy W, Hwang Seungyoung, Hai Xin, Melamed Michal L, Banerjee Tanushree, Coresh Josef, Powe Neil R
机构信息
Department of Medicine, Johns Hopkins University, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD.
Department of Medicine, Case Western University School of Medicine, Cleveland, OH.
出版信息
Am J Kidney Dis. 2017 Jul;70(1):48-58. doi: 10.1053/j.ajkd.2016.10.033. Epub 2017 Jan 12.
BACKGROUND
Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) are putative uremic toxins that may exert toxicity by a number of mechanisms, including impaired nitric oxide synthesis and generation of reactive oxygen species. The study goal was to determine the association between these metabolites and cardiovascular outcomes in hemodialysis patients.
STUDY DESIGN
Post hoc analysis of the Hemodialysis (HEMO) Study.
SETTING & PARTICIPANTS: 1,276 prevalent hemodialysis patients with available samples 3 to 6 months after randomization.
PREDICTOR
ADMA and SDMA measured in stored specimens.
OUTCOMES
Cardiac death, sudden cardiac death, first cardiovascular event, and any-cause death. Association with predictors analyzed using Cox regression adjusted for potential confounders (including demographics, clinical characteristics, comorbid conditions, albumin level, and residual kidney function).
RESULTS
Mean age of patients was 57±14 (SD) years, 63% were black, and 57% were women. Mean ADMA (0.9±0.2μmol/L) and SDMA levels (4.3±1.4μmol/L) were moderately correlated (r=0.418). Higher dialysis dose or longer session length were not associated with lower predialysis ADMA or SDMA concentrations. In fully adjusted models, each doubling of ADMA level was associated with higher risk (HR per 2-fold higher concentration; 95% CI) of cardiac death (1.83; 1.29-2.58), sudden cardiac death (1.79; 1.19-2.69), first cardiovascular event (1.50; 1.20-1.87), and any-cause death (1.44; 1.13-1.83). Compared to the lowest ADMA quintile (<0.745 μmol/L), the highest ADMA quintile (≥1.07μmol/L) was associated with higher risk (HR; 95% CI) of cardiac death (2.10; 1.44-3.05), sudden cardiac death (2.06; 1.46-2.90), first cardiovascular event (1.75; 1.35-2.27), and any-cause death (1.56; 1.21-2.00). SDMA level was associated with higher risk for cardiac death (HR, 1.40; 95% CI, 1.03-1.92), but this was no longer statistically significant after adjusting for ADMA level (HR, 1.20; 95% CI, 0.86-1.68).
LIMITATIONS
Single time-point measurement of ADMA and SDMA.
CONCLUSIONS
ADMA and, to a lesser extent, SDMA levels are associated with cardiovascular outcomes in hemodialysis patients.
背景
不对称二甲基精氨酸（ADMA）和对称二甲基精氨酸（SDMA）是公认的尿毒症毒素，可通过多种机制发挥毒性作用，包括一氧化氮合成受损和活性氧生成。本研究的目的是确定这些代谢产物与血液透析患者心血管结局之间的关联。
研究设计
血液透析（HEMO）研究的事后分析。
研究地点与参与者
1276例接受维持性血液透析的患者，在随机分组后3至6个月有可用样本。
预测指标
储存样本中检测到的ADMA和SDMA。
研究结局
心源性死亡、心源性猝死、首次心血管事件和全因死亡。使用Cox回归分析预测指标与结局之间的关联，并对潜在混杂因素（包括人口统计学、临床特征、合并症、白蛋白水平和残余肾功能）进行校正。
结果
患者的平均年龄为57±14（标准差）岁，63%为黑人，57%为女性。平均ADMA（0.9±0.2μmol/L）和SDMA水平（4.3±1.4μmol/L）呈中度相关（r=0.418）。较高的透析剂量或较长的透析时间与透析前较低的ADMA或SDMA浓度无关。在完全校正的模型中，ADMA水平每增加一倍，心源性死亡（每2倍浓度增加的风险比；95%置信区间）、心源性猝死（1.79；1.19-2.69）、首次心血管事件（1.50；1.20-1.87）和全因死亡（1.44；1.13-1.83）的风险就会升高。与最低ADMA五分位数（<0.745μmol/L）相比，最高ADMA五分位数（≥1.07μmol/L）的心源性死亡（2.10；1.44-3.05）、心源性猝死（2.06；1.46-2.90）、首次心血管事件（1.75；1.35-2.27）和全因死亡（1.56；1.21-2.00）风险更高。SDMA水平与心源性死亡风险较高相关（风险比，1.40；95%置信区间，1.03-1.92），但在调整ADMA水平后，这一相关性不再具有统计学意义（风险比，1.20；95%置信区间，0.86-1.68）。
局限性
ADMA和SDMA的单次时间点测量。
结论
ADMA以及程度较轻的SDMA水平与血液透析患者的心血管结局相关。
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