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Potential confounders in linking elevated S100A8/A9 to left ventricular dysfunction in septic shock patients

Matters Arising to this article was published on 02 January 2024

The Original Article was published on 29 September 2023

Jakobsson et al. investigated the role of S100A8/A9, a pro-inflammatory alarmin, in sepsis-induced myocardial dysfunction (SIMD). They concluded that elevated S100A8/A9 is associated with the development of left ventricular (LV) dysfunction in severe sepsis patients [1].

Patients 18 years of age and older admitted to the intensive care unit (ICU) with septic shock (per Sepsis III) were included in this study [1]. Thirty-five out of sixty-two (56%) patients had LV dysfunction. Plasma S100A8/A9 was significantly higher in LV dysfunction patients (20.1 μg/mL vs. 7.4 μg/mL, P = 0.009). Nearly half of critically ill patients, especially with septic shock, develop acute kidney injury (AKI), and 20–25% require renal replacement therapy (RRT) within the first ICU week [2]. Considering S100A8 (10.8 kDa) and S100A9 (13.2 kDa) molecular weights, as well as the molecular weight of the S100A8/A9 heterodimer (24 kDa) [3], continuous RRT (CRRT)—which has a cut-off value of 35–40 kDa—might eliminate these molecules, impacting bio marker levels, and potentially leading to artificially decreased S100A8/A9 levels [4, 5]. The absence of CRRT/RRT in the criteria and its impact on each group is a potential major comfounding factor that could heavily influence results [4, 5]. In a clinical setting, this could lead to inaccurate prognosis and unadapted support. It is necessary that a sensitivity analysis should be done after the exclusion of CRRT/RRT patients to clarify the performance of these biomarkers when they are not artificially removed by an extracorporeal purification technique [5].

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Left ventricular


Intensive care unit


Acute kidney injury


Renal replacement therapy


Continuous renal replacement therapy


  1. Jakobsson G, Papareddy P, Andersson H, et al. Therapeutic S100A8/A9 blockade inhibits myocardial and systemic inflammation and mitigates sepsis-induced myocardial dysfunction. Crit Care. 2023;27(1):374.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Peters E, Antonelli M, Wittebole X, et al. A worldwide multicentre evaluation of the influence of deterioration or improvement of acute kidney injury on clinical outcome in critically ill patients with and without sepsis at ICU admission: results from The Intensive Care Over Nations audit. Crit Care. 2018;22(1):188.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Sreejit G, Flynn MC, Patil M, Krishnamurthy P, Murphy AJ, Nagareddy PR. S100 family proteins in inflammation and beyond. Adv Clin Chem. 2020;98:173–231.

    Article  CAS  PubMed  Google Scholar 

  4. Honoré PM, Jacobs R, De Waele E, Van Gorp V, Spapen HD. Evaluating sepsis during continuous dialysis: are biomarkers still valid? Blood Purif. 2014;38(2):104–5.

    Article  PubMed  Google Scholar 

  5. Honore PM, Redant S, De Bels D. Reliability of biomarkers of sepsis during extracorporeal therapies: the clinician needs to know what is eliminated and what is not. Crit Care. 2020;24(1):553.

    Article  PubMed  PubMed Central  Google Scholar 

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PMH designed the paper. PMH, EP, and SB participated in drafting and reviewing. PMH, EP, and SB read and approved the final version of the manuscript.

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Correspondence to Patrick M. Honore.

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Honore, P.M., Perriens, E. & Blackman, S. Potential confounders in linking elevated S100A8/A9 to left ventricular dysfunction in septic shock patients. Crit Care 27, 480 (2023).

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