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

Abstract

IntroductionThe role of reactive carbonyl species, such as methylglyoxal (MG), has been overlooked within the context of the sepsis syndrome. The aims of this study were 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 and after 24 hours and 4, 7, 14, 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 with 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 = 0.018 for 90-day survival; **P = 0.008 for 28-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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-014-0683-x) contains supplementary material, which is available to authorized users.

Are there new approaches for diagnosis, therapy guidance and outcome prediction of sepsis?

“…Furthermore, physicians are confronted with various individual comorbidities and other influencing factors [164] . Lately, Brenner et al [165] showed the involvement of alternative mediators of cellular stress in the pathophysiology of sepsis. Methylglyoxal (MG), which is one of these highly reactive carbonyl species, is produced endogenously from the spontaneous degradation of triosephosphates (glyceraldehyde-3-phosphate and dihydroxyacetone phosphate) during glycolysis.…”

Evolving Evidence of Methylglyoxal and Dicarbonyl Stress Related Diseases from Diabetic to Non-Diabetic Models

“…Compared with routine diagnostic markers, MGO is a more useful marker of sepsis onset, development, and remission [20]. Sepsis is an infection accompanied by a systemic inflammatory response to the infection; this response causes multi-organ dysfunction even in uninfected organ systems; these events frequently lead to death [56].…”

“…However, direct measurement of tissue MGO requires biopsy or surgical tissue, and is not validated in humans. Plasma MGO levels, determined by HPLC, may prognosticate septic shock [20]. Testing MGO requires more clinical trials exploring its prognostic abilities and potential therapeutic applications.…”

“…They are well-known contributors to the development of diabetic complications. Recently, dicarbonyl stress has been established as a pathogenesis factor in diseases other than diabetes, such as renal failure [13][14][15][16][17], hypertension [18,19], and sepsis [20]. These diseases present normal blood sugar, yet they share some features with diabetes.…”

Can procalcitonin levels indicate the need for adjunctive therapies in sepsis?

“…However, no biomarker can answer all questions alone with 100% sensitivity and specificity in severe sepsis and septic shock owing to the overlapping pathomechanism of PAMPs and DAMPs discussed in detail above [29].…”