Symmetrical (SDMA) and asymmetrical dimethylarginine (ADMA) in sepsis: high plasma levels as combined risk markers for sepsis survival
Abstract Background Nitric oxide (NO) regulates processes involved in sepsis progression, including vascular and immune function. NO is generated by nitric oxide synthases (NOS) from L-arginine. Cellular L-arginine uptake is inhibited by symmetric dimethylarginine (SDMA) and asymmetric dimethylargin...
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doaj-2147e609a18340bfae10009959506e3a2020-11-25T02:42:47ZengBMCCritical Care1364-85352018-09-0122111010.1186/s13054-018-2090-1Symmetrical (SDMA) and asymmetrical dimethylarginine (ADMA) in sepsis: high plasma levels as combined risk markers for sepsis survivalMartin Sebastian Winkler0Axel Nierhaus1Gilbert Rösler2Susanne Lezius3Olaf Harlandt4Edzard Schwedhelm5Rainer H. Böger6Stefan Kluge7Department of Anesthesiology, University Medical Center Hamburg-EppendorfDepartment of Intensive Care Medicine, University Medical Center Hamburg-EppendorfDepartment of Intensive Care Medicine, University Medical Center Hamburg-EppendorfInstitute of Medical Biometry and Epidemiology, University Medical Center Hamburg-EppendorfDepartment of Internal Medicine II, Asklepios Klinik Nord-HeidbergInstitute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-EppendorfInstitute of Clinical Pharmacology and Toxicology, University Medical Center Hamburg-EppendorfDepartment of Intensive Care Medicine, University Medical Center Hamburg-EppendorfAbstract Background Nitric oxide (NO) regulates processes involved in sepsis progression, including vascular and immune function. NO is generated by nitric oxide synthases (NOS) from L-arginine. Cellular L-arginine uptake is inhibited by symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA) is a competitive inhibitor of NOS. Increased inhibitor blood concentrations lead to reduce NO bioavailability. The aim of this study was to determine whether plasma concentrations of SDMA and ADMA are markers for sepsis survival. Method This prospective, single center study involved 120 ICU patients with sepsis. Plasma SDMA and ADMA were measured on admission (day 1), day 3 and day 7 by mass spectrometry together with other laboratory markers. The sequential organ failure assessment (SOFA) score was used to evaluate sepsis severity. Survival was documented until day 28. Groups were compared using the Mann-Whitney U test, chi-squared test or non-parametric analysis of variance (ANOVA). Mortality was assessed using Kaplan-Meier curves and compared using the log-rank test. Specific risk groups were identified using a decision tree algorithm. Results Median plasma SDMA and ADMA levels were significantly higher in non-survivors than in survivors of sepsis: SDMA 1.14 vs. 0.82 μmol/L (P = 0.002) and ADMA 0.93 vs. 0.73 μmol/L (P = 0.016). ANOVA showed that increased plasma SDMA and ADMA concentrations were significantly associated with SOFA scores. The 28-day mortality was compared by chi-square test: for SDMA the mortality was 12% in the lower, 25% in the intermediate and 43% in the 75th percentile (P = 0.018); for ADMA the mortality was 18–20% in the lower and intermediate but 48% in the 75th percentile (P = 0.006). The highest mortality (61%) was found in patients with plasma SDMA > 1.34 together with ADMA levels > 0.97 μmol/L. Conclusions Increased plasma concentrations of SDMA and ADMA are associated with sepsis severity. Therefore, our findings suggest reduced NO bioavailability in non-survivors of sepsis. One may use individual SDMA and ADMA levels to identify patients at risk. In view of the pathophysiological role of NO we conclude that the vascular system and immune response are most severely affected when SDMA and ADMA levels are high.http://link.springer.com/article/10.1186/s13054-018-2090-1Symmetric dimethylarginineAsymmetric dimethylarginineSepsis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Martin Sebastian Winkler Axel Nierhaus Gilbert Rösler Susanne Lezius Olaf Harlandt Edzard Schwedhelm Rainer H. Böger Stefan Kluge |
spellingShingle |
Martin Sebastian Winkler Axel Nierhaus Gilbert Rösler Susanne Lezius Olaf Harlandt Edzard Schwedhelm Rainer H. Böger Stefan Kluge Symmetrical (SDMA) and asymmetrical dimethylarginine (ADMA) in sepsis: high plasma levels as combined risk markers for sepsis survival Critical Care Symmetric dimethylarginine Asymmetric dimethylarginine Sepsis |
author_facet |
Martin Sebastian Winkler Axel Nierhaus Gilbert Rösler Susanne Lezius Olaf Harlandt Edzard Schwedhelm Rainer H. Böger Stefan Kluge |
author_sort |
Martin Sebastian Winkler |
title |
Symmetrical (SDMA) and asymmetrical dimethylarginine (ADMA) in sepsis: high plasma levels as combined risk markers for sepsis survival |
title_short |
Symmetrical (SDMA) and asymmetrical dimethylarginine (ADMA) in sepsis: high plasma levels as combined risk markers for sepsis survival |
title_full |
Symmetrical (SDMA) and asymmetrical dimethylarginine (ADMA) in sepsis: high plasma levels as combined risk markers for sepsis survival |
title_fullStr |
Symmetrical (SDMA) and asymmetrical dimethylarginine (ADMA) in sepsis: high plasma levels as combined risk markers for sepsis survival |
title_full_unstemmed |
Symmetrical (SDMA) and asymmetrical dimethylarginine (ADMA) in sepsis: high plasma levels as combined risk markers for sepsis survival |
title_sort |
symmetrical (sdma) and asymmetrical dimethylarginine (adma) in sepsis: high plasma levels as combined risk markers for sepsis survival |
publisher |
BMC |
series |
Critical Care |
issn |
1364-8535 |
publishDate |
2018-09-01 |
description |
Abstract Background Nitric oxide (NO) regulates processes involved in sepsis progression, including vascular and immune function. NO is generated by nitric oxide synthases (NOS) from L-arginine. Cellular L-arginine uptake is inhibited by symmetric dimethylarginine (SDMA) and asymmetric dimethylarginine (ADMA) is a competitive inhibitor of NOS. Increased inhibitor blood concentrations lead to reduce NO bioavailability. The aim of this study was to determine whether plasma concentrations of SDMA and ADMA are markers for sepsis survival. Method This prospective, single center study involved 120 ICU patients with sepsis. Plasma SDMA and ADMA were measured on admission (day 1), day 3 and day 7 by mass spectrometry together with other laboratory markers. The sequential organ failure assessment (SOFA) score was used to evaluate sepsis severity. Survival was documented until day 28. Groups were compared using the Mann-Whitney U test, chi-squared test or non-parametric analysis of variance (ANOVA). Mortality was assessed using Kaplan-Meier curves and compared using the log-rank test. Specific risk groups were identified using a decision tree algorithm. Results Median plasma SDMA and ADMA levels were significantly higher in non-survivors than in survivors of sepsis: SDMA 1.14 vs. 0.82 μmol/L (P = 0.002) and ADMA 0.93 vs. 0.73 μmol/L (P = 0.016). ANOVA showed that increased plasma SDMA and ADMA concentrations were significantly associated with SOFA scores. The 28-day mortality was compared by chi-square test: for SDMA the mortality was 12% in the lower, 25% in the intermediate and 43% in the 75th percentile (P = 0.018); for ADMA the mortality was 18–20% in the lower and intermediate but 48% in the 75th percentile (P = 0.006). The highest mortality (61%) was found in patients with plasma SDMA > 1.34 together with ADMA levels > 0.97 μmol/L. Conclusions Increased plasma concentrations of SDMA and ADMA are associated with sepsis severity. Therefore, our findings suggest reduced NO bioavailability in non-survivors of sepsis. One may use individual SDMA and ADMA levels to identify patients at risk. In view of the pathophysiological role of NO we conclude that the vascular system and immune response are most severely affected when SDMA and ADMA levels are high. |
topic |
Symmetric dimethylarginine Asymmetric dimethylarginine Sepsis |
url |
http://link.springer.com/article/10.1186/s13054-018-2090-1 |
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