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

In established acute kidney injury (AKI), serum creatinine poorly differentiates prerenal and intrinsic AKI. A damage-associated nephron biomarker, neutrophil gelatinase-associated lipocalin (NGAL) could be a better discriminator. We tested the hypothesis that urinary NGAL distinguishes intrinsic and prerenal AKI, and tested its performance in the prediction of a composite outcome that included progression to a higher RIFLE (“risk, injury, failure, loss of function, end stage renal disease”) severity class, dialysis, or death. We measured urinary NGAL in 161 hospitalized patients with established AKI using a standardized clinical platform. We excluded 16 patients with postrenal obstruction or insufficient clinical information. Of the remaining 145 patients, 75 patients had intrinsic AKI, 32 patients had prerenal AKI, and 38 patients could not be classified. We found that urinary NGAL levels effectively discriminated intrinsic AKI from prerenal AKI (ROC 0.87, CI 0.81-0.94). An NGAL level >104 μg/L indicated intrinsic AKI (likelihood ratio 5.97), while an NGAL level <47 μg/L made intrinsic AKI unlikely (likelihood ratio 0.2). Patients experiencing the composite outcome had higher median urinary NGAL levels on inclusion (248.2 vs. 68.3 μg/L, p<0.001). In logistic regression analysis, NGAL independently predicted the composite outcome, when corrected for demographics, co-morbidities, creatinine, and RIFLE class. Hence, urinary NGAL is useful in classifying and stratifying patients with established AKI.

IntroductionNeutrophil gelatinase−associated lipocalin (NGAL) is a widely studied biomarker of renal tubular injury. Urinary NGAL (uNGAL) during acute kidney injury (AKI) predicts short-term adverse outcomes. However, the long-term predictive value is unknown.MethodsWe performed a prospective observational study of 145 patients with hospital-acquired AKI according to Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease (RIFLE) criteria and analyzed the long-term predictive value of uNGAL at the time of AKI. We defined a composite outcome of all-cause mortality and the development of end-stage renal disease (ESRD).ResultsIn all, 61 AKI patients died and 22 developed ESRD within 6 months. The uNGAL levels were significantly higher in patients with poor long-term outcomes. uNGAL levels ≥362 μg/l (highest quartile) and uNGAL levels between 95 and 362 μg/l (third quartile) were associated with hazard ratios of 3.7 (95% confidence interval, 2.1–6.5) and 1.9 (1.1–3.5), respectively, compared with uNGAL levels <95 μg/l (lower quartiles). After 6 months, 67% and 43% of patients within the highest and third uNGAL quartile, respectively, had either progressed to ESRD or died, compared to only 21% of patients with uNGAL in the lower 2 quartiles (P < 0.001). In multivariable Cox regression analyses accounting for conventional predictors, uNGAL was the strongest independent predictor of adverse long-term outcomes. The association of uNGAL levels and poor long-term outcomes remained significant in the subgroup of 107 AKI survivors discharged without requiring dialysis (P = 0.002).DiscussionThese data indicate that elevated uNGAL levels at AKI diagnosis predict poor long-term outcomes.