The ratio of arginine to dimethylarginines is reduced and predicts outcomes in patients with severe sepsis

Division of Pulmonary and Critical Care Medicine, Department of Nursing, University of Rochester Medical Center, Rochester, NY, USA.
Critical care medicine (Impact Factor: 6.31). 03/2011; 39(6):1351-8. DOI: 10.1097/CCM.0b013e318212097c
Source: PubMed


Arginine deficiency may contribute to microvascular dysfunction, but previous studies suggest that arginine supplementation may be harmful in sepsis. Systemic arginine availability can be estimated by measuring the ratio of arginine to its endogenous inhibitors, asymmetric and symmetric dimethylarginine. We hypothesized that the arginine-to-dimethylarginine ratio is reduced in patients with severe sepsis and associated with severity of illness and outcomes.
Case-control and prospective cohort study.
Medical and surgical intensive care units of an academic medical center.
One hundred nine severe sepsis and 50 control subjects.
Plasma and urine were obtained in control subjects and within 48 hrs of diagnosis in severe sepsis patients. The arginine-to-dimethylarginine ratio was higher in control subjects vs. sepsis patients (median, 95; interquartile range, 85-114; vs. median, 34; interquartile range, 24-48; p < .001) and in hospital survivors vs. nonsurvivors (median, 39; interquartile range, 26-52; vs. median, 27; interquartile range, 19-32; p = .004). The arginine-to-dimethylarginine ratio was correlated with Acute Physiology and Chronic Health Evaluation II score (Spearman's correlation coefficient [ρ] = - 0.40; p < .001) and organ-failure free days (ρ = 0.30; p = .001). A declining arginine-to-dimethylarginine ratio was independently associated with hospital mortality (odds ratio, 1.63 per quartile; 95% confidence interval, 1.00-2.65; p = .048) and risk of death over the course of 6 months (hazard ratio, 1.41 per quartile; 95% confidence interval, 1.01-1.98; p = .043). The arginine-to-dimethylarginine ratio was correlated with the urinary nitrate-to-creatinine ratio (ρ = 0.46; p < .001).
The arginine-to-dimethylarginine ratio is associated with severe sepsis, severity of illness, and clinical outcomes. The arginine-to-dimethylarginine ratio may be a useful biomarker, and interventions designed to augment systemic arginine availability in severe sepsis may still be worthy of investigation.

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Available from: Brian Thomas Graves, Jan 16, 2014
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    • "The pathogenesis of MODS in patients with septic shock is a multifactorial process. Recent studies have provided evidence that an impaired NO homeostasis might play an important role [2] [3] [4]. Dysfunctions of the L-arg/NO pathway have been reported to be a reason for the deleterious vascular effects of diabetes mellitus, hypercholesterolemia, hypertension, smoking, and others [5]. "
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    ABSTRACT: Dysfunctions of the L-arginine (L-arg)/nitric-oxide (NO) pathway are suspected to be important for the pathogenesis of multiple organ dysfunction syndrome (MODS) in septic shock. Therefore plasma concentrations of L-arg and asymmetric dimethylarginine (ADMA) were measured in 60 patients with septic shock, 30 surgical patients and 30 healthy volunteers using enzyme linked immunosorbent assay (ELISA) kits. Plasma samples from patients with septic shock were collected at sepsis onset, and 24 h, 4 d, 7 d, 14 d and 28 d later. Samples from surgical patients were collected prior to surgery, immediately after the end of the surgical procedure as well as 24 h later and from healthy volunteers once. In comparison to healthy volunteers and surgical patients, individuals with septic shock showed significantly increased levels of ADMA, as well as a decrease in the ratio of L-arg and ADMA at all timepoints. In septic patients with an acute liver failure (ALF), plasma levels of ADMA and L-arg were significantly increased in comparison to septic patients with an intact hepatic function. In summary it can be stated, that bioavailability of NO is reduced in septic shock. Moreover, measurements of ADMA and L-arg appear to be early predictors for survival in patients with sepsis-associated ALF.
    Mediators of Inflammation 05/2012; 2012:210454. DOI:10.1155/2012/210454 · 3.24 Impact Factor
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    • "A medical history of hypertension, hyperlipidemia, smoking, diabetes mellitus, coronary artery disease, age, gender, mean arterial pressure, and the Charlson comorbidity index were considered potentially important covariables that could be associated with brachial artery reactivity and severe sepsis [29,39-41]. These covariables and the presence or absence of vasopressor infusions (at the time of brachial artery measurements) were considered potentially important covariables that could be associated with brachial artery reactivity and hospital mortality. "
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