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Abstract

Introduction: Circulating concentrations of plasma inflammatory and apoptosis markers in critically ill patients with acute kidney injury requiring renal replacement therapy (RRT) are associated with RRT dependence and death. Whether these biomarkers predict clinical outcomes is unknown. Methods: The Biological Markers for Recovery of Kidney was a multicenter, prospective, nested, observational study conducted ancillary to the Veterans Affairs/Acute Renal Failure Trial Network study of 817 critically ill patients receiving RRT. Plasma markers were measured on day 1. Renal recovery was defined as alive and RRT independent by day 60. A parsimonious clinical model was determined using stepwise logistic regression and Least Absolute Shrinkage and Selection Operator (LASSO) based algorithms. We computed area under receiver operating characteristic curve (AUROC), integrated discrimination index (IDI), and category-free net reclassification index (CFNRI). Results: Of the 817 patients, 298 (36.5%) were alive and free of RRT and 415 (50.8%) died. The derivation (model building) and validation sets contained 394 and 423 subjects. In the validation dataset, a clinical model consisting of eight clinical variables (age, mechanical ventilation, arterial ph, bilirubin, platelets,mean arterial pressure, and Total ApacheII) predicted renal recovery and mortality (AUROC range: 0.74–0.77 and 0.75–0.80); with good calibration (P values range: 0.08–0.45); modest increment in IDI (ranges: 2%-5%, P values <0.05); and CFNRI (ranges: 27%-32%, p values <0.05). The AUROC of individual biomarkers were only modestly predictive of renal recovery, (range, 0.55–0.63) and mortality, (range 0.54–0.68). When added to the clinical model there was an increase in risk prediction for renal mortaltiy (AUROC, 0.78–0.82); but not for recovery (AUROC, 0.76–0.78); IDI (1%-2%: P value < 0.05) and CFNRI (27%-23%) for recovery and mortality. Conclusions: In a large cohort of severely ill patients with acute kidney injury requiring RRT, the addition of plasma inflammatory and apoptosis markers to a baseline clinical model resulted in a modest improvement in risk prediction of RRT independence and mortality.