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.
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.
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尿液和血浆 ADMA 与糖尿病肾病中 DKD 心血管疾病风险的动脉粥样硬化风险的关联：慢性肾功能不全队列 (CRIC) 研究的结果。
DOI：
10.1093/ndt/gfad103
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Towns
中科院分区：
文献类型：
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作者：
Schrauben,SarahJ;Sapa,Hima;Xie,Dawei;Zhang,Xiaoming;Anderson,AmandaHyre;Shlipak,MichaelG;Hsu,Chi-Yuan;Shafi,Tariq;Mehta,Rupal;Bhat,Zeenat;Brown,Julie;Charleston,Jeanne;Chen,Jing;He,Jiang;Ix,JoachimH;Rao,Pandurango;Towns
慢性肾脏病(CKD)与动脉粥样硬化性心血管疾病(ASCVD)的风险相关，尤其是在糖尿病患者中。CKD[不对称二甲基精氨酸(ADMA)、对称性二甲基精氨酸(SDMA)和三甲胺N-氧化物(TMAO)]中累积的溶质代谢的改变可能反映了CKD与ASCVD之间的联系。方法这项病例队列研究包括慢性肾功能不全的队列参与者，他们有基线糖尿病，估计的肾小球滤过率和1.73m2；每个结局都没有既往病史。主要结果是发生ASCVD(首次心肌梗死、中风或外周动脉疾病事件的时间)，次要结果是发生心力衰竭。子队列包括随机选择的符合入选标准的参与者。血浆和尿液中ADMA、SDMA和TMAO浓度用液相色谱-串联质谱法测定。结果血浆ADMA浓度(每标准差)与ASCVD风险相关[危险比(HR)1.30，95%可信区间(CI)1.01-1.68]。ADMA排泄量较低(按标准差)与ASCVD风险相关(HR 1.42，95%CI 1.07~1.89)。ADMA排泄分数最低的四分位数与较高的四分位数相比有更高的ASCVD风险(HR 2.25，95%CI 1.08-4.69)。血浆SDMA和TMAO浓度及排泄分数与ASCVD无关。ADMA、SDMA和TMAO的血浆和部分排泄均与心力衰竭无关。结论ADMA肾脏排泄减少导致血浆浓度升高和ASCVD风险增加。
BackgroundChronic 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 trimethylamineN-oxide (TMAO)] may reflect pathways linking CKD with ASCVD.MethodsThis 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.ResultsHigher 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.ConclusionThese data suggest that decreased kidney excretion of ADMA leads to increased plasma concentrations and ASCVD risk.