Circulating levels of soluble Fas (sCD95) are associated with risk for development of a non-resolving acute kidney injury sub-phenotype

Abstract

ABSTRACT: Background Critically ill patients with acute kidney injury (AKI) can be divided into two sub-phenotypes, resolving or non-resolving, based on the trajectory of serum creatinine. It is unknown if the biology underlying these two AKI recovery patterns is different. Study Design Prospective longitudinal cohort study. Settings and Participants A cohort of 1240 patients with systemic inflammatory response syndrome and admitted to the intensive care unit at Harborview Medical Center, Seattle, Washington. Predictor Eight circulating biomarkers were measured using meso scale discovery technology. 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). Outcome Acute kidney injury sub-phenotypes based on trajectory of serum creatinine. Results During the first 3 days of ICU admission, 802 (65%) subjects developed AKI; 492 (61%) had a resolving sub-phenotype and 310 (39%) had a non-resolving sub-phenotype. The non-resolving sub-phenotype was associated with higher mortality (adjusted RR 2.4 (95% CI 1.5, 3.9)), while the resolving sub-phenotype was not associated with an increased risk of death (adjusted RR 1.2 (95% CI 0.7, 2.1)). Soluble Fas was the only biomarker associated with a non-resolving sub-phenotype after adjustment for age, body mass index, diabetes and acute physiology and chronic health evaluation III scores (p < .001). Limitations Misclassification and secondary analysis. Conclusions Identifying modifiable targets in the Fas-mediated pathway may lead to strategies for prevention and treatment of a clinically important form of AKI.