尿和血浆 ADMA 与糖尿病肾病心血管疾病风险中的动脉粥样硬化风险的关联：来自慢性肾功能不全队列（CRIC）研究的结果。
Association of urine and plasma ADMA with atherosclerotic risk in DKD cardiovascular disease risk in diabetic kidney disease: findings from the Chronic Renal Insufficiency Cohort (CRIC) study.
机构信息
Department of Medicine, Perelman School of Medicine, Center for Clinical Epidemiology and Biostatistics at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
出版信息
Nephrol Dial Transplant. 2023 Nov 30;38(12):2809-2815. doi: 10.1093/ndt/gfad103.
BACKGROUND
Chronic kidney disease (CKD) is associated with atherosclerotic cardiovascular disease (ASCVD) risk, especially among those with diabetes. Altered metabolism of solutes that accumulate in CKD [asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and trimethylamine N-oxide (TMAO)] may reflect pathways linking CKD with ASCVD.
METHODS
This case-cohort study included Chronic Renal Insufficiency Cohort participants with baseline diabetes, estimated glomerular filtration rate <60 mL/min/1.73 m2, and without prior history for each outcome. The primary outcome was incident ASCVD (time to first myocardial infarction, stroke or peripheral artery disease event) and secondary outcome was incident heart failure. The subcohort comprised randomly selected participants meeting entry criteria. Plasma and urine ADMA, SDMA and TMAO concentrations were determined by liquid chromatography-tandem mass spectrometry. Associations of uremic solute plasma concentrations and urinary fractional excretions with outcomes were evaluated by weighted multivariable Cox regression models, adjusted for confounding covariables.
RESULTS
Higher plasma ADMA concentrations (per standard deviation) were associated with ASCVD risk [hazard ratio (HR) 1.30, 95% confidence interval (CI) 1.01-1.68]. Lower fractional excretion of ADMA (per standard deviation) was associated with ASCVD risk (HR 1.42, 95% CI 1.07-1.89). The lowest quartile of ADMA fractional excretion was associated with greater ASCVD risk (HR 2.25, 95% CI 1.08-4.69) compared with the highest quartile. Plasma SDMA and TMAO concentration and fractional excretion were not associated with ASCVD. Neither plasma nor fractional excretion of ADMA, SDMA and TMAO were associated with incident heart failure.
CONCLUSION
These data suggest that decreased kidney excretion of ADMA leads to increased plasma concentrations and ASCVD risk.
背景
慢性肾脏病（CKD）与动脉粥样硬化性心血管疾病（ASCVD）风险相关，尤其是在糖尿病患者中。在 CKD 中积累的溶质代谢物（不对称二甲基精氨酸（ADMA）、对称二甲基精氨酸（SDMA）和三甲胺 N-氧化物（TMAO））的改变可能反映了将 CKD 与 ASCVD 联系起来的途径。
方法
本病例-队列研究纳入了基线时有糖尿病、估算肾小球滤过率 <60 mL/min/1.73 m2 且每种结局均无既往病史的慢性肾功能不全队列参与者。主要结局是 ASCVD 事件（首次心肌梗死、中风或外周动脉疾病事件）的发生，次要结局是心力衰竭的发生。子队列由符合入选标准的随机选择的参与者组成。通过液相色谱-串联质谱法测定血浆和尿液 ADMA、SDMA 和 TMAO 浓度。通过加权多变量 Cox 回归模型评估尿毒症溶质血浆浓度和尿分数排泄与结局的相关性，调整混杂协变量。
结果
较高的血浆 ADMA 浓度（每标准差）与 ASCVD 风险相关（风险比 [HR] 1.30，95%置信区间 [CI] 1.01-1.68）。ADMA 尿分数排泄的每标准差降低与 ASCVD 风险相关（HR 1.42，95% CI 1.07-1.89）。与最高四分位相比，ADMA 尿分数排泄最低四分位与 ASCVD 风险增加相关（HR 2.25，95% CI 1.08-4.69）。ADMA、SDMA 和 TMAO 的血浆浓度和尿分数排泄与 ASCVD 均无相关性。ADMA、SDMA 和 TMAO 的血浆或尿分数排泄均与心力衰竭的发生无关。
结论
这些数据表明，ADMA 的肾脏排泄减少导致血浆浓度增加和 ASCVD 风险增加。
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