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Am J Kidney Dis. 2017 Jul;70(1):48-58. doi: 10.1053/j.ajkd.2016.10.033. Epub 2017 Jan 12.

Serum Asymmetric and Symmetric Dimethylarginine and Morbidity and Mortality in Hemodialysis Patients.

Author information

1
Department of Medicine, Johns Hopkins University, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD. Electronic address: tshafi@jhmi.edu.
2
Department of Medicine, Case Western University School of Medicine, Cleveland, OH.
3
Department of Medicine, Palo Alto Veterans Affairs Health Care System and Stanford University, Palo Alto, CA.
4
Department of Medicine, Johns Hopkins University, Baltimore, MD.
5
Department of Medicine, Albert Einstein College of Medicine, Bronx, NY; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY.
6
Department of Medicine, University of California, San Francisco, CA.
7
Department of Medicine, Johns Hopkins University, Baltimore, MD; Welch Center for Prevention, Epidemiology and Clinical Research, Johns Hopkins University, Baltimore, MD; Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD; Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD.

Abstract

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±0.2μmol/L) and SDMA levels (4.3±1.4μmol/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 (≥1.07μmol/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.

KEYWORDS:

Cardiovascular mortality; asymmetric dimethylarginine (ADMA); cardiac death; cardiovascular morbidity; dialysis outcomes; end-stage renal disease (ESRD); hemodialysis; sudden cardiac death; symmetric dimethylarginine (SDMA); uremic toxins

PMID:
28089476
PMCID:
PMC5483385
DOI:
10.1053/j.ajkd.2016.10.033
[Indexed for MEDLINE]
Free PMC Article

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