Kidney biomarkers and major adverse kidney events in critically ill patients

Background: Several biomarkers of acute kidney injury (AKI) have been examined for their ability to predict AKI earlier than serum creatinine. Few studies have focused on using kidney biomarkers to better predict major adverse kidney events (MAKE), an increasingly used composite outcome in critical care nephrology research. Methods: Single-center prospective study collecting blood and urine samples from critically ill patients with AKI KDIGO stage 2 or above, and matched controls from a single, tertiary care intensive care unit. Samples were collected at 24-48 hours after AKI diagnosis (cases) or ICU admission (controls), 5-7 days later, and 4-6 weeks following discharge for AKI patients. The primary outcome of interest was MAKE at hospital discharge. Results: Serum/urinary neutrophil gelatinase-associated lipocalin, serum/urinary cystatin C, and urinary kidney injury molecule-1 early in the AKI or ICU course were all significantly higher in patients with MAKE compared to those not experiencing MAKE at hospital discharge. Serum cystatin C, and to a lesser extent serum NGAL, significantly improved upon a clinical prediction model of MAKE as assessed by the area under the receiver operating characteristic curve. Patients without MAKE experienced a greater decline in serum NGAL from initial measurement to second measurement than those patients experiencing MAKE. Conclusion: Early measures of kidney biomarkers in critically ill patients are associated with MAKE. This relationship appears to be greatest with serum NGAL and cystatin C, which display additive utility to a clinical prediction model. Trending serum NGAL may also have utility in predicting MAKE.