Diagnostic and prognostic stratification in the emergency department using urinary biomarkers of nephron damage: a multicenter prospective cohort study

Abstract

Objectives: This study aimed to determine the diagnostic and prognostic value of urinary biomarkers of intrinsic acute kidney injury (AKI) when patients were triaged in the emergency department.

Background: Intrinsic AKI is associated with nephron injury and results in poor clinical outcomes. Several urinary biomarkers have been proposed to detect and measure intrinsic AKI.

Methods: In a multicenter prospective cohort study, 5 urinary biomarkers (urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, urinary liver-type fatty acid binding protein, urinary interleukin-18, and cystatin C) were measured in 1,635 unselected emergency department patients at the time of hospital admission. We determined whether the biomarkers diagnosed intrinsic AKI and predicted adverse outcomes during hospitalization.

Results: All biomarkers were elevated in intrinsic AKI, but urinary neutrophil gelatinase-associated lipocalin was most useful (81% specificity, 68% sensitivity at a 104-ng/ml cutoff) and predictive of the severity and duration of AKI. Intrinsic AKI was strongly associated with adverse in-hospital outcomes. Urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule 1 predicted a composite outcome of dialysis initiation or death during hospitalization, and both improved the net risk classification compared with conventional assessments. These biomarkers also identified a substantial subpopulation with low serum creatinine at hospital admission, but who were at risk of adverse events.

Conclusions: Urinary biomarkers of nephron damage enable prospective diagnostic and prognostic stratification in the emergency department.

Figure 1. Study Flow Chart

Patients from 3 emergency departments were recruited at the time of hospital admission and urine samples were collected. Urinary biomarkers were measured and correlated with the renal diagnosis and the subsequent hospital course. AH-NYPH = Allen Hospital of New York-Presbyterian Hospital; AKI = acute kidney injury; CKD = chronic kidney disease; ESRD = end-stage renal disease; RRT = renal replacement therapy; SIUH = Staten Island University Hospital; uCysC = urinary cystatin C; uIL = urinary interleukin; uKIM = urinary kidney injury molecule; uL-FABP = urinary liver-type fatty acid binding protein; uNGAL = urinary neutrophil gelatinase-associated lipocalin.

Figure 2. Urinary Biomarker Levels in the Diagnostic Classification of Emergency Department Patients

uNGAL, uKIM-1, uL-FABP, uIL-18, and uCysC were compared by analysis of variance in adjudicated patients with normal kidney function (Norm), stable CKD, pAKI, and iAKI (p values in upper left hand corners of each graph). Biomarkers differed significantly in patients with iAKI compared with all other adjudicated groups (*p < 0.05, **p < 0.01, ***p < 0.001 by post-hoc Tukey test). All diagrams represent geometric means with 95% confidence intervals. iAKI = intrinsic acute kidney injury; pAKI = prerenal acute kidney injury; sCr = serum creatinine; Uncl = unclassified; other abbreviations as in Figure 1.

Figure 3. Risk Stratification by Serum Creatinine and Urinary Biomarkers

Rates of clinical events (initiation of dialysis or in-hospital mortality) in patients stratified by admission sCr and uNGAL (A) or sCr and uKIM-1 (B). Cutoffs were applied at the 75th percentile for each biomarker (sCr, 1.4 mg/dl; uNGAL, 104 ng/ml; uKIM-1, 2.82 ng/ml). Significance level was determined by Pearson's chi-square test. ***p < 0.001, **p < 0.01. Abbreviations as in Figures 1 and 2.