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2017 ; 70
(1
): 48-58
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Serum Asymmetric and Symmetric Dimethylarginine and Morbidity and Mortality in
Hemodialysis Patients
#MMPMID28089476
Shafi T
; Hostetter TH
; Meyer TW
; Hwang S
; Hai X
; Melamed ML
; Banerjee T
; Coresh J
; Powe NR
Am J Kidney Dis
2017[Jul]; 70
(1
): 48-58
PMID28089476
show ga
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?mol/L) and SDMA levels (4.3±1.4?mol/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 ?mol/L),
the highest ADMA quintile (?1.07?mol/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.
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