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

被引:10
作者
Schrauben, Sarah J. [1 ,2 ]
Sapa, Hima [3 ]
Xie, Dawei [2 ]
Zhang, Xiaoming [2 ]
Anderson, Amanda Hyre [2 ,4 ]
Shlipak, Michael G. [5 ]
Hsu, Chi-yuan [6 ]
Shafi, Tariq [7 ]
Mehta, Rupal [8 ]
Bhat, Zeenat [9 ]
Brown, Julie [10 ]
Charleston, Jeanne [11 ]
Chen, Jing [12 ]
He, Jiang
Ix, Joachim H. [13 ]
Rao, Pandurango [14 ]
Townsend, Ray [1 ]
Kimmel, Paul L. [15 ]
Vasan, Ramachandran S. [16 ]
Feldman, Harold, I [1 ,17 ]
Seegmiller, Jesse C. [18 ]
Brunengraber, Henri [19 ,20 ]
Hostetter, Thomas H. [21 ]
Schelling, Jeffrey R. [22 ,23 ]
机构
[1] Univ Penn, Ctr Clin Epidemiol & Biostat, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA
[2] Univ Penn, Dept Biostat Epidemiol & Informat, Perelman Sch Med, Philadelphia, PA 19104 USA
[3] CSL Seqirus, Holly Springs, NC USA
[4] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA USA
[5] San Francisco Vet Affairs Healthcare Syst, Kidney Hlth Res Collaborat, San Francisco, CA USA
[6] Univ Calif San Francisco, Dept Med, Div Nephrol, San Francisco, CA USA
[7] Houston Methodist Hosp, Dept Med, Div Nephrol, Houston, TX USA
[8] Northwestern Univ, Dept Med, Div Nephrol & Hypertens, Chicago, IL USA
[9] Wayne State Univ, Dept Med, Detroit, MI USA
[10] Univ Illinois, Dept Med, Chicago, IL USA
[11] Johns Hopkins Sch Med, Dept Internal Med, Sect Nephrol, Baltimore, MD USA
[12] Tulane Univ, Dept Med, Sch Med, New Orleans, LA USA
[13] Univ Calif San Diego, Dept Med, Div Nephrol Hypertens, Sch Med, San Diego, CA USA
[14] Univ Michigan, Dept Med, Div Nephrol, Ann Arbor, MI USA
[15] Natl Inst Diabet & Digest & Kidney Dis, Div Kidney Urol & Hematol Dis, Bethesda, MD USA
[16] Univ Texas San Antonio, Sch Publ Hlth, San Antonio, TX USA
[17] Patient Ctr Outcomes Res Inst, Washington, DC USA
[18] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN USA
[19] Case Western Univ, Dept Nutr, Sch Med, Cleveland, OH USA
[20] Case Western Univ, Dept Biochem, Sch Med, Cleveland, OH USA
[21] Univ N Carolina, Dept Med, Div Nephrol, Chapel Hill, NC USA
[22] Case Western Reserve Univ, Dept Physiol & Biophys, Sch Med, Cleveland, OH USA
[23] Case Western Reserve Univ, Dept Med, Sch Med, Cleveland, OH USA
关键词
biomarker; cardiovascular disease; chronic kidney disease; diabetes; uremic solutes; TRIMETHYLAMINE-N-OXIDE; ASYMMETRIC DIMETHYLARGININE; MORTALITY; METABOLISM; PHOSPHATIDYLCHOLINE; EVENTS;
D O I
10.1093/ndt/gfad103
中图分类号
R3 [基础医学]; R4 [临床医学];
学科分类号
1001 ; 1002 ; 100602 ;
摘要
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 m(2), 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.
引用
收藏
页码:2809 / 2815
页数:7
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