TY - JOUR
T1 - Association of urine and plasma ADMA with atherosclerotic risk in DKD cardiovascular disease risk in diabetic kidney disease
T2 - Findings from the Chronic Renal Insufficiency Cohort (CRIC) study
AU - Schrauben, Sarah J.
AU - Sapa, Hima
AU - Xie, Dawei
AU - Zhang, Xiaoming
AU - Anderson, Amanda Hyre
AU - Shlipak, Michael G.
AU - Hsu, Chi Yuan
AU - Shafi, Tariq
AU - Mehta, Rupal
AU - Bhat, Zeenat
AU - Brown, Julie
AU - Charleston, Jeanne
AU - Chen, Jing
AU - He, Jiang
AU - Ix, Joachim H.
AU - Rao, Pandurango
AU - Townsend, Ray
AU - Kimmel, Paul L.
AU - Vasan, Ramachandran S.
AU - Feldman, Harold I.
AU - Seegmiller, Jesse C.
AU - Brunengraber, Henri
AU - Hostetter, Thomas H.
AU - Schelling, Jeffrey R.
N1 - Publisher Copyright:
© 2023 The Author(s). Published by Oxford University Press on behalf of the ERA.
PY - 2023/12/1
Y1 - 2023/12/1
N2 - 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.
AB - 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.
KW - biomarker
KW - cardiovascular disease
KW - chronic kidney disease
KW - diabetes
KW - uremic solutes
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U2 - 10.1093/ndt/gfad103
DO - 10.1093/ndt/gfad103
M3 - Article
C2 - 37230949
AN - SCOPUS:85178649032
SN - 0931-0509
VL - 38
SP - 2809
EP - 2815
JO - Nephrology Dialysis Transplantation
JF - Nephrology Dialysis Transplantation
IS - 12
ER -
