TY - JOUR
T1 - Serum Asymmetric and Symmetric Dimethylarginine and Morbidity and Mortality in Hemodialysis Patients
AU - Shafi, Tariq
AU - Hostetter, Thomas H.
AU - Meyer, Timothy W.
AU - Hwang, Seungyoung
AU - Hai, Xin
AU - Melamed, Michal L.
AU - Banerjee, Tanushree
AU - Coresh, Josef
AU - Powe, Neil R.
N1 - Funding Information:
Support: This study was supported by R01-DK-080123 (NIDDK). Drs Shafi (K23-DK-083514 and R03-DK-104012) and Powe (in part by R01-DK-080123 and K24 DK002643) were supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.
Publisher Copyright:
© 2016 National Kidney Foundation, Inc.
PY - 2017/7
Y1 - 2017/7
N2 - Background Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) are putative uremic toxins that may exert toxicity by a number of mechanisms, including impaired nitric oxide synthesis and generation of reactive oxygen species. The study goal was to determine the association between these metabolites and cardiovascular outcomes in hemodialysis patients. Study Design Post hoc analysis of the Hemodialysis (HEMO) Study. Setting & Participants 1,276 prevalent hemodialysis patients with available samples 3 to 6 months after randomization. Predictor ADMA and SDMA measured in stored specimens. Outcomes Cardiac death, sudden cardiac death, first cardiovascular event, and any-cause death. Association with predictors analyzed using Cox regression adjusted for potential confounders (including demographics, clinical characteristics, comorbid conditions, albumin level, and residual kidney function). Results Mean age of patients was 57 ± 14 (SD) years, 63% were black, and 57% were women. Mean ADMA (0.9 ± 0.2 μmol/L) and SDMA levels (4.3 ± 1.4 μmol/L) were moderately correlated (r = 0.418). Higher dialysis dose or longer session length were not associated with lower predialysis ADMA or SDMA concentrations. In fully adjusted models, each doubling of ADMA level was associated with higher risk (HR per 2-fold higher concentration; 95% CI) of cardiac death (1.83; 1.29-2.58), sudden cardiac death (1.79; 1.19-2.69), first cardiovascular event (1.50; 1.20-1.87), and any-cause death (1.44; 1.13-1.83). Compared to the lowest ADMA quintile (<0.745 μmol/L), the highest ADMA quintile (≥1.07 μmol/L) was associated with higher risk (HR; 95% CI) of cardiac death (2.10; 1.44-3.05), sudden cardiac death (2.06; 1.46-2.90), first cardiovascular event (1.75; 1.35-2.27), and any-cause death (1.56; 1.21-2.00). SDMA level was associated with higher risk for cardiac death (HR, 1.40; 95% CI, 1.03-1.92), but this was no longer statistically significant after adjusting for ADMA level (HR, 1.20; 95% CI, 0.86-1.68). Limitations Single time-point measurement of ADMA and SDMA. Conclusions ADMA and, to a lesser extent, SDMA levels are associated with cardiovascular outcomes in hemodialysis patients.
AB - Background Asymmetric (ADMA) and symmetric dimethylarginine (SDMA) are putative uremic toxins that may exert toxicity by a number of mechanisms, including impaired nitric oxide synthesis and generation of reactive oxygen species. The study goal was to determine the association between these metabolites and cardiovascular outcomes in hemodialysis patients. Study Design Post hoc analysis of the Hemodialysis (HEMO) Study. Setting & Participants 1,276 prevalent hemodialysis patients with available samples 3 to 6 months after randomization. Predictor ADMA and SDMA measured in stored specimens. Outcomes Cardiac death, sudden cardiac death, first cardiovascular event, and any-cause death. Association with predictors analyzed using Cox regression adjusted for potential confounders (including demographics, clinical characteristics, comorbid conditions, albumin level, and residual kidney function). Results Mean age of patients was 57 ± 14 (SD) years, 63% were black, and 57% were women. Mean ADMA (0.9 ± 0.2 μmol/L) and SDMA levels (4.3 ± 1.4 μmol/L) were moderately correlated (r = 0.418). Higher dialysis dose or longer session length were not associated with lower predialysis ADMA or SDMA concentrations. In fully adjusted models, each doubling of ADMA level was associated with higher risk (HR per 2-fold higher concentration; 95% CI) of cardiac death (1.83; 1.29-2.58), sudden cardiac death (1.79; 1.19-2.69), first cardiovascular event (1.50; 1.20-1.87), and any-cause death (1.44; 1.13-1.83). Compared to the lowest ADMA quintile (<0.745 μmol/L), the highest ADMA quintile (≥1.07 μmol/L) was associated with higher risk (HR; 95% CI) of cardiac death (2.10; 1.44-3.05), sudden cardiac death (2.06; 1.46-2.90), first cardiovascular event (1.75; 1.35-2.27), and any-cause death (1.56; 1.21-2.00). SDMA level was associated with higher risk for cardiac death (HR, 1.40; 95% CI, 1.03-1.92), but this was no longer statistically significant after adjusting for ADMA level (HR, 1.20; 95% CI, 0.86-1.68). Limitations Single time-point measurement of ADMA and SDMA. Conclusions ADMA and, to a lesser extent, SDMA levels are associated with cardiovascular outcomes in hemodialysis patients.
KW - asymmetric dimethylarginine (ADMA)
KW - cardiac death
KW - cardiovascular morbidity
KW - Cardiovascular mortality
KW - dialysis outcomes
KW - end-stage renal disease (ESRD)
KW - hemodialysis
KW - sudden cardiac death
KW - symmetric dimethylarginine (SDMA)
KW - uremic toxins
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U2 - 10.1053/j.ajkd.2016.10.033
DO - 10.1053/j.ajkd.2016.10.033
M3 - Article
C2 - 28089476
AN - SCOPUS:85009822267
VL - 70
SP - 48
EP - 58
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
SN - 0272-6386
IS - 1
ER -