Evaluation of Biomarkers in Sepsis: High Dimethylarginine (ADMA and SDMA) Concentrations Are Associated with Mortality

J Appl Lab Med. 2021 Apr 29;6(3):592-605. doi: 10.1093/jalm/jfaa156.

Abstract

Background: As modulators of nitric oxide generation, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) may play important roles in sepsis. Current data on dimethylarginines are conflicting, and direct comparison data with other biomarkers are limited.

Methods: Fifty-five patients were included in the final analysis and were divided into 4 groups: infection without sepsis, sepsis, severe sepsis, and septic shock. The first available samples on hospital admission were analyzed for ADMA, SDMA, procalcitonin (PCT), C-reactive protein, heparin binding protein (HBP), zonulin, soluble CD25 (sCD25), and soluble CD163 (sCD163). White blood cell (WBC) counts and lactate results were obtained from the medical record.

Results: There were no statistically significant differences in ADMA and SDMA concentrations among the 4 groups; however, PCT, WBC, HBP, and sCD25 showed statistically significant differences. Lactate only trended toward statistical significance, likely because of limited availability in the medical record. Differences between survivors of sepsis and nonsurvivors at 30 days were highly statistically significant for ADMA and SDMA. Areas under the curve (AUCs) for ROC analysis were 0.88 and 0.95, respectively. There was also a statistically significant difference between survivors of sepsis and nonsurvivors for HBP, lactate, sCD25, and sCD163; however, AUCs for ROC curves were not statistically significantly different from 0.5.

Conclusions: Analysis of biomarkers other than dimethylarginines were in general agreement with expectations from the literature. ADMA and SDMA may not be specific markers for diagnosis of sepsis; however, they may be useful in short-term mortality risk assessment.

Keywords: ADMA; C-reactive protein; SDMA; heparin binding protein; procalcitonin; sepsis; soluble CD163; soluble CD25; survival; zonulin.

MeSH terms

  • Arginine / analogs & derivatives
  • Biomarkers
  • Humans
  • Sepsis* / diagnosis

Substances

  • Biomarkers
  • dimethylarginine
  • symmetric dimethylarginine
  • N,N-dimethylarginine
  • Arginine