Abstract | BACKGROUND: METHODS: We undertook a secondary analysis of data and samples collected during the Vasopressin versus noradrenaline as initial therapy in septic shock (VANISH) trial. Plasma and DNA samples isolated from 286 patients recruited into the VANISH trial were analysed. Concentrations of L-Arginine and the methylarginines ADMA and symmetric dimethylarginine (SDMA) were determined from plasma samples. Whole blood and buffy-coat samples were genotyped for polymorphisms of DDAH2. Clinical data collected during the study were used to explore the relationship between circulating methylarginines, genotype and outcome. RESULTS: Peak ADMA concentration over the study period was associated with a hazard ratio for death at 28 days of 3.3 (95% CI 2.0-5.4), p < 0.001. Reduced DDAH activity measured by an elevated ADMA:SDMA ratio was associated with a reduced risk of death in septic shock (p = 0.03). The rs805305 polymorphism of DDAH2 was associated with reduced DDAH activity (p = 0.004) and 28-day mortality (p = 0.02). Mean SOFA score and shock duration were also reduced in the less common G:G genotype compared to heterozygotes and C:C genotype patients (p = 0.04 and p = 0.02, respectively). CONCLUSIONS: Plasma ADMA is a biomarker of outcome in septic shock, and reduced DDAH activity is associated with a protective effect. The polymorphism rs805305 SNP is associated with reduced mortality, which is potentially mediated by reduced DDAH2 activity. TRIAL REGISTRATION: ISRCTN Registry, ISRCTN20769191 . Registered on 20 September 2012.
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Authors | Simon Lambden, James Tomlinson, Sophie Piper, Anthony C Gordon, James Leiper |
Journal | Critical care (London, England)
(Crit Care)
Vol. 22
Issue 1
Pg. 336
(12 11 2018)
ISSN: 1466-609X [Electronic] England |
PMID | 30538005
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Biomarkers
- Protective Agents
- symmetric dimethylarginine
- N,N-dimethylarginine
- Arginine
- Amidohydrolases
- dimethylargininase
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Topics |
- Amidohydrolases
(analysis, blood)
- Arginine
(analogs & derivatives, analysis, blood)
- Biomarkers
(analysis, blood)
- Humans
- Organ Dysfunction Scores
- Polymorphism, Single Nucleotide
(physiology)
- Protective Agents
(analysis)
- Shock, Septic
(enzymology, mortality, physiopathology)
- Statistics, Nonparametric
- Time Factors
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