Abstract
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.
Highlights
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
We present results of analyses based on testing of whether circulating levels of biomarkers representative of two main biologic pathways, endothelial dysfunction and inflammation/apoptosis, are differentially associated with AKI subphenotypes in a cohort of intensive care unit (ICU) patients with the systemic inflammatory response syndrome (SIRS)
In multivariate analyses adjusting for potential confounders known to be associated with circulating biomarker levels and risk for AKI, including age, diabetes mellitus, body mass index, and APACHE Acute Physiology and Chronic Health Evaluation III (III) scores [1, 2, 34] (Table 4), we found that only Soluble Fas (sFas) levels were associated with a nonresolving, as opposed to a resolving, AKI subphenotype after Bonferroni correction
Summary
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. Primarily in animal models, has implicated different biologic processes, such as apoptosis, inflammation, and endothelial dysfunction, in the pathogenesis of AKI [14,15,16,17] It is not yet known whether these different pathophysiologic processes might contribute to the development of a nonresolving as opposed to a resolving AKI subphenotype
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