Combining Novel Renal Injury Markers with Delta Serum Creatinine Early after Cardiac Surgery and Risk-Stratification for Serious Adverse Outcomes: An Exploratory Analysis

Objective: To evaluate the prognostic utility of multiple novel urinary biomarkers of renal injury when used alone, in pair-wise combination with an early delta serum creatinine (Delta S-Cr) term, and combined as a broad biomarker panel for the prediction of serious adverse outcomes that may reflect AM in patients undergoing cardiac surgery. Design: Post-hoc analysis of prospective observational study. Setting: Academic medical center. Participants: 603 adults undergoing cardiac surgery. Interventions: None. Measurements and Main Results: Urinary cystatin-c, kidney injury molecule-1, chemokine (C-C motif) ligand 2 and interleukin-18 were measured at baseline and < 1 hour, 3 hours and 18-24 hours after separation from cardiopulmonary bypass (CPB). Delta S-Crinitial was defined as the difference in Sr from baseline to first postoperative measure. The primary outcome of hospital mortality or renal replacement therapy occurred in 25 patients. Concordant elevation of any urinary biomarker measured 3 hours after CPB together with Delta S-Crinitial >= 0 mg.dL(-1) provided excellent early risk stratification for the primary outcome (OR > 15.1, 95% CI 4.1-55.4). Combining four urinary biomarkers together with and neutrophil gelatinase-associated lipocalin, previously reported from the same cohort, to provide a 6-point AM risk score enabled early identification of patients reaching the primary outcome (ROCAUC 0.86, 95% CI 0.79-0.92) with potentially useful sensitivity and specificity at varied cut-points. Conclusions: Combining novel urinary biomarkers of renal injury with a creatinine-based metric soon after cardiac surgery provided excellent prognostic utility for serious adverse outcomes. Future studies are required to confirm these findings and determine optimal biomarker combinations for cost-effective risk stratification. (C) 2018 Elsevier Inc. All rights reserved.