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. 2017 Aug 17;21(1):217.
doi: 10.1186/s13054-017-1807-x.

Circulating levels of soluble Fas (sCD95) are associated with risk for development of a nonresolving acute kidney injury subphenotype

Pavan K Bhatraju  1 , Cassianne Robinson-Cohen  2 , Carmen Mikacenic  3 , Susanna Harju-Baker  3 , Victoria Dmyterko  3 , Natalie S J Slivinski  4 , W Conrad Liles  5 , Jonathan Himmelfarb  2 , Susan R Heckbert  6 , Mark M Wurfel  3
Affiliations

Circulating levels of soluble Fas (sCD95) are associated with risk for development of a nonresolving acute kidney injury subphenotype

Pavan K Bhatraju et al. Crit Care. .

Abstract

Background: Critically ill patients with acute kidney injury (AKI) can be divided into two subphenotypes, resolving or nonresolving, on the basis of the trajectory of serum creatinine. It is unknown if the biology underlying these two AKI recovery patterns is different.

Methods: We measured eight circulating biomarkers in plasma obtained from a cohort of patients admitted to an intensive care unit (ICU) (n = 1241) with systemic inflammatory response syndrome. The biomarkers were representative of several biologic processes: apoptosis (soluble Fas), inflammation (soluble tumor necrosis factor receptor 1, interleukin 6, interleukin 8) and endothelial dysfunction, (angiopoietin 1, angiopoietin 2, and soluble vascular cell adhesion molecule 1). We tested for associations between biomarker levels and AKI subphenotypes using relative risk regression accounting for multiple hypotheses with the Bonferroni correction.

Results: During the first 3 days of ICU admission, 868 (70%) subjects developed AKI; 502 (40%) had a resolving subphenotype, and 366 (29%) had a nonresolving subphenotype. Hospital mortality was 12% in the resolving subphenotype and 21% in the nonresolving subphenotype. Soluble Fas was the only biomarker associated with a nonresolving subphenotype after adjustment for age, body mass index, diabetes, and Acute Physiology and Chronic Health Evaluation III score (p = 0.005).

Conclusions: Identifying modifiable targets in the Fas-mediated pathway may lead to strategies for prevention and treatment of a clinically important form of AKI.

Keywords: Acute kidney injury; Apoptosis; Biomarkers.

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Conflict of interest statement

Consent for publication

No individual personal data are included in the study. All patients provided necessary consent to participate in this study.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1
Fig. 1
Soluble Fas (sFas) biomarker levels in the study cohort. Box plots showing median, interquartile range (box), and upper and lower adjacent values (bars) for biomarker levels, stratified by no acute kidney injury (AKI), resolving acute kidney injury, and nonresolving acute kidney injury. p Value is for comparison of resolving with nonresolving AKI
See this image and copyright information in PMC

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