Biomarker Enhanced Risk Prediction for Adverse Outcomes in Critically Ill Patients Receiving RRT

Higher plasma concentrations of inflammatory and apoptosis markers in critically ill patients receiving RRT are associated with RRT dependence and death. This study objective was to examine whether plasma inflammatory (IL-6, -8, -10, and -18; macrophage migration inhibitory factor) and apoptosis (death receptor-5, tumor necrosis factor receptor I and II) biomarkers augment risk prediction of renal recovery and mortality compared with clinical models. The Biologic Markers of Recovery for the Kidney study (n=817) was a prospective, nested, observational cohort study conducted as an ancillary to the Veterans Affairs/National Institutes of Health Acute renal failure Trial Network study, a randomized trial of intensive versus less intensive RRT in critically ill patients with AKI conducted between November 2003 and July 2007 at 27 Veterans Affairs- and university-affiliated centers. Primary outcomes of interest were renal recovery and mortality at day 60. A parsimonious clinical model consisting of only four variables (age, mean arterial pressure, mechanical ventilation, and bilirubin) predicted renal recovery (area under the receiver-operating characteristic curve [AUROC], 0.73; 95% confidence interval [95% CI], 0.68 to 0.78) and mortality (AUROC, 0.74; 95% CI, 0.69 to 0.78). By contrast, individual biomarkers were only modestly predictive of renal recovery (AUROC range, 0.55-0.63) and mortality (AUROC range, 0.54-0.68). Adding plasma IL-8 to a parsimonious model augmented prediction of recovery (AUROC, 0.76; 95% CI, 0.71 to 0.81; P=0.04) and mortality (AUROC, 0.78; 95% CI, 0.73 to 0.82; P