Plasma neutrophil gelatinase-associated lipocalin as a single test rule out biomarker for acute kidney injury: A cross-sectional study in patients admitted to the emergency department

Abstract

Objectives: Acute kidney injury (AKI) is a syndrome with high mortality and morbidity in part due to delayed recognition based on changes in creatinine. A marker for AKI based on a single measurement is needed and therefore the performance of a single measurement of plasma neutrophil gelatinase-associated lipocalin (pNGAL) to predict AKI in patients admitted to the emergency department was tested.

Methods: Samples from the Triage study which included 6005 consecutive adult patients admitted to the emergency department were tested for pNGAL. The optimal cutoff for pNGAL was determined by the AUC and compared to AKI based on creatinine using different estimations of the premorbid kidney function.

Results: In 4833 patients, two or more plasma creatinine (pCr) measurements were available allowing the detection of AKI. The highest prevalence of AKI (10%) was found when defining AKI as an increase in pCr ≥26.5 μmol/L from the prior year's mean pCr. At these conditions the AUC for pNGAL to predict AKI was 85% giving an optimal cutoff of 142.5 ng/mL with a negative predictive value of 0.96, a positive predictive value of 0.35, a specificity of 0.87 and a sensitivity of 0.70.

Conclusion: The study illustrates that the value of a single measurement of pNGAL is primarily in excluding AKI whereas it`s poorer in predicting the presence of AKI. When diagnosing AKI with pCr the optimal baseline pCr level is the mean of available pCr (mb-pCr) measurements from up to a year prior to the current event.

Fig 1. A timeline illustrating the assessment of premorbid kidney function.

A timeline illustrating the assessment of premorbid kidney function using baseline plasma creatinine (b-pCr) and mean baseline plasma creatinine (mb-pCr). If available, the lowest pCr measurement within seven days prior to study inclusion established the baseline. When no pCr measurement was available within this seven-day window, the mean of all pCr measurements taken up to 365 days before ED admission (mb-pCr) represented the kidney baseline.

Fig 2. Flowchart over patient inclusion for the acute kidney injury (AKI) cohort and distribution between acute kidney injury- diagnostic criteria (AKI-DC) I- IV.

Abbreviation: AKI = acute kidney injury; pCr = plasma creatinine; AKI-DC = acute kidney injury–diagnostic criteria.

Fig 3. Flowchart over patient inclusion for the pNGAL cohort and distribution between acute kidney injury- diagnostic criteria (AKI-DC) I-IV.

Abbreviation: AKI = acute kidney injury; non-AKI = non- acute kidney injury; pCr = plasma creatinine; AKI-DC = acute kidney injury–diagnostic criteria.

Fig 4. Receiver Operating Characteristic (ROC) curves for acute kidney injury- diagnostic criteria (AKI-DC) I-IV.

ROC analyses were used to calculate area under the curve (AUC) for each AKI-DC (I-IV) to determine the optimal NGAL cutoff to diagnose acute kidney injury (AKI). AUC for AKI-DC I was acceptable and for AKI-DC II-IV excellent.