Methylglyoxal as a new biomarker in patients with septic shock: an observational clinical study

Thorsten Brenner, Thomas Fleming, Florian Uhle, Stephan Silaff, Felix Schmitt, Eduardo Salgado, Alexis Ulrich, Stefan Zimmermann, Thomas Bruckner, Eike Martin, Angelika Bierhaus, Peter P Nawroth, Markus A Weigand, Stefan Hofer

IntroductionThe role of reactive carbonyl species, such as methylglyoxal (MG) has been overlooked within the context of the sepsis syndrome. The aim of this study was to assess the impact of MG formation in different inflammatory settings and to evaluate its use for early diagnosis as well as prognosis of the sepsis syndrome.MethodsIn total, 120 patients in three groups were enrolled in this observational clinical pilot study. The three groups included patients with septic shock (n =60), postoperative controls (n =30) and healthy volunteers (n =30). Plasma samples from patients with septic shock were collected at sepsis onset, after 24 hours, 4 days, 7 days, 14 days and 28 days. Plasma samples from postoperative controls were collected prior to surgery, immediately following the end of the surgical procedure as well as 24 hours later, and from healthy volunteers once. Plasma levels of MG were determined by high-performance liquid chromatography. Additionally, plasma levels of procalcitonin, C-reactive protein, soluble CD14 subtype and interleukin-6 were determined.ResultsPatients with septic shock showed significantly higher plasma levels of MG at all measured times, compared to postoperative controls. MG was found to identify patients with septic shock more effectively (area under the curve (AUC): 0.993) than procalcitonin (AUC: 0.844), C-reactive protein (AUC: 0.791), soluble CD14 subtype (AUC: 0.832) and interleukin-6 (AUC: 0.898) as assessed by receiver operating characteristic (ROC) analysis. Moreover, plasma levels of MG in non-survivors were significantly higher than in survivors (sepsis onset: P =0.008** for 28-day survival; P =0.018* for 90-day survival). Plasma levels of MG proved to be an early predictor for survival in patients with septic shock (sepsis onset: ROC-AUC 0.710 for 28-day survival; ROC-AUC 0.686 for 90-day survival).ConclusionsMG was identified as a marker for monitoring the onset, development and remission of sepsis, and was found to be more useful than routine diagnostic markers. Further studies are required to determine the extent of MG modification in sepsis and whether targeting this pathway could be therapeutically beneficial to the patient.Trial registrationGerman Clinical Trials Register DRKS00000505. Registered 8 November 2010.