Drew David A, Tighiouart Hocine, Scott Tammy, Kantor Amy, Fan Li, Artusi Carlo, Plebani Mario, Weiner Daniel E, Sarnak Mark J
Division of Nephrology, Department of Medicine.
Institute for Clinical Research and Health Policy Studies, and Tufts Clinical and Translational Science Institute, Tufts University, Boston, Massachusetts; and.
Clin J Am Soc Nephrol. 2014 Aug 7;9(8):1426-33. doi: 10.2215/CJN.00770114. Epub 2014 Jun 26.
Levels of asymmetric dimethylarginine, an inhibitor of nitric oxide synthase, are elevated in kidney disease and associated with mortality in white European hemodialysis populations. Nitric oxide production and degradation are partially genetically determined and differ by racial background. No studies have measured asymmetric dimethylarginine in African Americans on dialysis and assessed whether differences exist in its association with mortality by race.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Asymmetric dimethylarginine was measured in 259 patients on maintenance hemodialysis assembled from 2004 to 2012 in Boston area outpatient centers. Cox proportional hazards models were used to determine the association between asymmetric dimethylarginine and all-cause mortality, and an interaction with race was tested.
Mean (SD) age was 63 (17) years, 46% were women, and 22% were African American. Mean asymmetric dimethylarginine in non-African Americans was 0.79 µmol/L (0.16) versus 0.70 µmol/L (0.11) in African Americans (P<0.001); 130 patients died over a median follow-up of 2.3 years. African Americans had lower mortality risk than non-African Americans (hazard ratio, 0.27; 95% confidence interval, 0.15 to 0.50) that was robust to adjustment for age, comorbidity, and asymmetric dimethylarginine (hazard ratio, 0.35; 95% confidence interval, 0.17 to 0.69). An interaction was noted between race and asymmetric dimethylarginine (P=0.03), such that asymmetric dimethylarginine was associated with higher mortality in non-African Americans (adjusted hazard ratio, 1.29; 95% confidence interval, 1.06 to 1.57 per 1 SD higher asymmetric dimethylarginine) but not in African Americans (adjusted hazard ratio, 0.57; 95% confidence interval, 0.28 to 1.18). Additional adjustment for fibroblast growth factor 23 partially attenuated the association for non-African Americans (adjusted hazard ratio, 1.22; 95% confidence interval, 0.98 to 1.50).
African Americans have lower asymmetric dimethylarginine levels and lower hazard for mortality compared with non-African Americans. Levels of asymmetric dimethylarginine did not explain lower hazard for mortality in non-African American patients. High asymmetric dimethylarginine was a risk factor for mortality exclusively in non-African Americans. Mechanisms explaining these relationships need to be evaluated.
不对称二甲基精氨酸是一氧化氮合酶的抑制剂，其水平在肾脏疾病中升高，并且与欧洲裔白人血液透析人群的死亡率相关。一氧化氮的产生和降解部分由基因决定，并且因种族背景而异。尚无研究测量过接受透析治疗的非裔美国人的不对称二甲基精氨酸水平，也未评估其与死亡率的关联是否因种族而异。
设计、场所、参与者及测量方法：对2004年至2012年在波士顿地区门诊中心接受维持性血液透析的259例患者测量了不对称二甲基精氨酸。采用Cox比例风险模型确定不对称二甲基精氨酸与全因死亡率之间的关联，并检验其与种族的相互作用。
平均（标准差）年龄为63（17）岁，46%为女性，22%为非裔美国人。非裔美国人的平均不对称二甲基精氨酸水平为0.70 μmol/L（0.11），而非非裔美国人的为0.79 μmol/L（0.16）（P<0.001）；在中位随访2.3年期间，有130例患者死亡。非裔美国人的死亡风险低于非非裔美国人（风险比为0.27；95%置信区间为0.15至0.50），在对年龄、合并症和不对称二甲基精氨酸进行校正后该结果依然稳健（风险比为0.35；95%置信区间为0.17至0.69）。注意到种族与不对称二甲基精氨酸之间存在相互作用（P=0.03），即不对称二甲基精氨酸与非裔美国人较高的死亡率相关（校正后风险比为1.29；不对称二甲基精氨酸每升高1个标准差，95%置信区间为1.06至1.57），但与非裔美国人的死亡率无关（校正后风险比为0.57；95%置信区间为0.28至1.18）。对成纤维细胞生长因子23进行额外校正后，非裔美国人的关联有所减弱（校正后风险比为1.22；95%置信区间为0.98至1.50）。
与非裔美国人相比，非裔美国人的不对称二甲基精氨酸水平较低，死亡风险也较低。不对称二甲基精氨酸水平并不能解释非裔美国患者较低的死亡风险。高不对称二甲基精氨酸仅是非裔美国人死亡的一个风险因素。需要评估解释这些关系的机制。
