• Pavan K Bhatraju, Cassianne Robinson-Cohen, Carmen Mikacenic, Susanna Harju-Baker, Victoria Dmyterko, Natalie S J Slivinski, W Conrad Liles, Jonathan Himmelfarb, Susan R Heckbert, and Mark M Wurfel.
• Pulmonary and Critical Care Medicine, University of Washington, Harborview Medical Center, 325 9th Avenue, Seattle, WA, 98104, USA. bhatraju@uw.edu.
• Crit Care. 2017 Aug 17; 21 (1): 217.

BackgroundCritically 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.MethodsWe 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.ResultsDuring 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).ConclusionsIdentifying modifiable targets in the Fas-mediated pathway may lead to strategies for prevention and treatment of a clinically important form of AKI.

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