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

Critical Care

Susan R. Heckbert¹  W. Conrad Liles²  Cassianne Robinson-Cohen³  Jonathan Himmelfarb³  Victoria Dmyterko⁴  Susanna Harju-Baker⁴  Pavan K. Bhatraju⁴  Carmen Mikacenic⁴  Mark M. Wurfel⁴  Natalie S. J. Slivinski⁵ 

[1] Department of Epidemiology, University of Washington;Department of Medicine, University of Washington, Harborview Medical Center;Kidney Research Institute, Division of Nephrology, University of Washington;Pulmonary and Critical Care Medicine, University of Washington, Harborview Medical Center;University of Leeds;

关键词: Apoptosis;    Acute kidney injury;    Biomarkers;   

DOI  :  10.1186/s13054-017-1807-x

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown