We read with great interest the article by van Oers et al. who conclude that baseline and serial mid-regional proadrenomedullin (MR-proADM) had a good ability to predict 28-day mortality in critically ill patients with SARS-CoV-2 pneumonia [1]. Indeed, MR-proADM was 1.88 for survivors and 1.01 nmol/L for non-survivors (p = 0.001) [1]. We would also like to highlight the validity of MR-proADM measurements during continuous renal replacement therapy (CRRT) [2]. Indeed, when looking at Table 1 with the characteristics of patients with SARS-CoV-2 pneumonia with regards to survival up to 28 days, we see that CRRT is used in 5.3% of the survivors versus 14.7% of the non-survivors and even though p value was 0.06, CRRT was used three times more in the non-survivor group [1]. MR-proADM molecular weight (MW) is between 4 and 5.5 kDa [3], and, therefore, it may also be removed by CRRT. Indeed, Mueller et al. showed a significant decrease in MR-proADM (45–65%) if a high-flux membrane was used (with a cut-off of 35,000 Da) [4]. This cut-off is similar to what is used in contemporary CRRT membranes [5]. Hence, among CRRT patients plasma levels of MR-proADM could be falsely low due to elimination by CRRT. Also, as CRRT was seen to be used three times more in non-survivors (14.7%) versus non-survivors (5.3), the level could be artificially lower due to removal by CRRT. Knowing that the difference between survivors and non-survivors was quiet small (1.88 in survivors vs 1.01 nmol/L in non-survivors, it stands to reason that CRRT, which is most frequently used in the non-survivors, could have artificially lowered the level of MR-proADM. With no doubt, this could be seen as a potential confounder in this study and could put the results somewhat in balance.
Author's contributions
PMH,SM, SR, DDB designed the paper. All authors participated in drafting and reviewing. All authors read and approved the final version of the manuscript.
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Competing interests
The authors declare to have no competing interests.
Acknowledgements
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References
- 1.van Oers J.A.H., Kluiters Y., Bons J.A.P., et al. Endothelium-associated biomarkers mid-regional proadrenomedullin and C-terminal proendothelin-1 have good ability to predict 28-day mortality in critically ill patients with SARS-CoV-2 pneumonia: a prospective cohort study. J Crit Care. 2021 Jul 20 doi: 10.1016/j.jcrc.2021.07.017. S0883-9441(21)00157-X. Epub ahead of print. PMID: 34340901; PMCID: PMC8289696. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Honore P.M., 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 Sep 11;24(1):553. doi: 10.1186/s13054-020-03277-8. PMID: 32917263; PMCID: PMC7483498. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Önal U., Valenzuela-Sánchez F., Vandana K.E., et al. Mid-regional pro-adrenomedullin (MR-proADM) as a biomarker for sepsis and septic shock: narrative review. Healthcare (Basel) 2018 Sep 3;6(3):110. doi: 10.3390/healthcare6030110. PMID: 30177659; PMCID: PMC6164535. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Mueller T., Gegenhuber A., Kronabethleitner G., et al. Plasma concentrations of novel cardiac biomarkers before and after hemodialysis session. Clin Biochem. 2015;48:1163–1166. doi: 10.1016/j.clinbiochem.2015.07.031. [DOI] [PubMed] [Google Scholar]
- 5.Honore P.M., Spapen H.D. What a clinician should know about a renal replacement membrane? J Transl Int Med. 2018 Jun 26;6(2):62–65. doi: 10.2478/jtim-2018-0016. PMID: 29984198; PMCID: PMC6032186. [DOI] [PMC free article] [PubMed] [Google Scholar]
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