Heunisch Fabian, Chaykovska Lyubov, von Einem Gina, Alter Markus, Dschietzig Thomas, Kretschmer Axel, Kellner Karl-Heinz, Hocher Berthold
Center for Cardiovascular Research, Charité Universitaetsmedizin Berlin, Berlin, Germany Clinic for Cardiovascular Surgery, University Hospital Zurich, Zurich, Switzerland Department of Nephrology, Campus Benjamin Franklin, Charité Universitaetsmedizin Berlin, Berlin Immundiagnostik AG, Bensheim Department of Cardiology and Angiology Bayer Pharma AG, Wuppertal Neuroimmun GmbH, Karlsruhe Institute for Nutritional Science, University of Potsdam, Potsdam IFLb Laboratoriumsmedizin Berlin GmbH, Berlin, Germany Department of Basic Medicine, Medical College of Hunan Normal University, Changsha, China.
Medicine (Baltimore). 2017 Feb;96(6):e6065. doi: 10.1097/MD.0000000000006065.
Asymmetric dimethylarginine (ADMA) is a competitive inhibitor of the nitric oxide (NO)-synthase and a biomarker of endothelial dysfunction (ED). ED plays an important role in the pathogenesis of contrast-induced nephropathy (CIN). The aim of our study was to evaluate serum ADMA concentration as a biomarker of an acute renal damage during the follow-up of 90 days after contrast medium (CM) application.Blood samples were obtained from 330 consecutive patients with diabetes mellitus or mild renal impairment immediately before, 24 and 48 hours after the CM application for coronary angiography. The patients were followed for 90 days. The composite endpoints were major adverse renal events (MARE) defined as occurrence of death, initiation of dialysis, or a doubling of serum creatinine concentration.Overall, ADMA concentration in plasma increased after CM application, although, there was no differences between ADMA levels in patients with and without CIN. ADMA concentration 24 hours after the CM application was predictive for dialysis with a specificity of 0.889 and sensitivity of 0.653 at values higher than 0.71 μmol/L (area under the curve: 0.854, 95% confidential interval: 0.767-0.941, P < 0.001). This association remained significant in multivariate Cox regression models adjusted for relevant factors of long-term renal outcome. 24 hours after the CM application, ADMA concentration in plasma was predictive for MARE with a specificity of 0.833 and sensitivity of 0.636 at a value of more than 0.70 μmol/L (area under the curve: 0.750, 95% confidence interval: 0.602-0.897, P = 0.004). Multivariate logistic regression analysis confirmed that ADMA and anemia were significant predictors of MARE. Further analysis revealed that increased ADMA concentration in plasma was highly significant predictor of MARE in patients with CIN. Moreover, patients with CIN and MARE had the highest plasma ADMA levels 24 hours after CM exposure in our study cohort. The impact of ADMA on MARE was independent of such known CIN risk factors as anemia, pre-existing renal failure, pre-existing heart failure, and diabetes.ADMA concentration in plasma is a promising novel biomarker of major contrast-induced nephropathy-associated events 90 days after contrast media exposure.
不对称二甲基精氨酸（ADMA）是一氧化氮（NO）合酶的竞争性抑制剂，也是内皮功能障碍（ED）的生物标志物。ED在造影剂诱导的肾病（CIN）发病机制中起重要作用。我们研究的目的是评估血清ADMA浓度作为造影剂（CM）应用后90天随访期间急性肾损伤生物标志物的价值。在330例连续的糖尿病或轻度肾功能损害患者行冠状动脉造影应用CM前、应用后24小时和48小时采集血样。对患者进行90天随访。复合终点为主要不良肾脏事件（MARE），定义为死亡、开始透析或血清肌酐浓度翻倍。总体而言，应用CM后血浆中ADMA浓度升高，不过，发生CIN和未发生CIN的患者ADMA水平无差异。应用CM后24小时的ADMA浓度对透析具有预测价值，当值高于0.71μmol/L时，特异性为0.889，敏感性为0.653（曲线下面积：0.854，95%可信区间：0.767 - 0.941，P<0.001）。在针对长期肾脏结局相关因素进行校正的多变量Cox回归模型中，这种关联仍然显著。应用CM后24小时，血浆中ADMA浓度对MARE具有预测价值，当值高于0.70μmol/L时，特异性为0.833，敏感性为0.636（曲线下面积：0.750，95%可信区间：0.602 - 0.897，P = 0.004）。多变量逻辑回归分析证实，ADMA和贫血是MARE的显著预测因素。进一步分析显示，血浆中ADMA浓度升高是CIN患者MARE的高度显著预测因素。此外，在我们的研究队列中，发生CIN和MARE的患者在应用CM后24小时血浆ADMA水平最高。ADMA对MARE的影响独立于贫血、既往肾衰竭、既往心力衰竭和糖尿病等已知的CIN危险因素。血浆中ADMA浓度是造影剂暴露后90天主要造影剂诱导的肾病相关事件有前景的新型生物标志物。
