Impact of clinical context on acute kidney injury biomarker performances: differences between neutrophil gelatinase-associated lipocalin and L-type fatty acid-binding protein.

Toshifumi Asada,Ryota Inokuchi,Kent Doi,Naoki Yahagi,Masaomi Nangaku,Rei Isshiki,Maki Sumida,Eisei Noiri,Naoki Hayase

doi:10.1038/srep33077

Abstract

Application of acute kidney injury (AKI) biomarkers with consideration of nonrenal conditions and systemic severity has not been sufficiently determined. Herein, urinary neutrophil gelatinase-associated lipocalin (NGAL), L-type fatty acid-binding protein (L-FABP) and nonrenal disorders, including inflammation, hypoperfusion and liver dysfunction, were evaluated in 249 critically ill patients treated at our intensive care unit. Distinct characteristics of NGAL and L-FABP were revealed using principal component analysis: NGAL showed linear correlations with inflammatory markers (white blood cell count and C-reactive protein), whereas L-FABP showed linear correlations with hypoperfusion and hepatic injury markers (lactate, liver transaminases and bilirubin). We thus developed a new algorithm by combining urinary NGAL and L-FABP with stratification by the Acute Physiology and Chronic Health Evaluation score, presence of sepsis and blood lactate levels to improve their AKI predictive performance, which showed a significantly better area under the receiver operating characteristic curve [AUC-ROC 0.940; 95% confidential interval (CI) 0.793–0.985] than that under NGAL alone (AUC-ROC 0.858, 95% CI 0.741–0.927, P = 0.03) or L-FABP alone (AUC-ROC 0.837, 95% CI 0.697–0.920, P = 0.007) and indicated that nonrenal conditions and systemic severity should be considered for improved AKI prediction by NGAL and L-FABP as biomarkers.

Highlights

34 patients were diagnosed with chronic kidney disease (CKD) before admission to the intensive care unit (ICU)
To examine whether changes in urinary neutrophil gelatinase-associated lipocalin (NGAL) and L-type fatty acid-binding protein (L-FABP) levels were distinct in relation to nonrenal disorders, we evaluated their relationship with C-reactive protein levels and white blood cell counts for systemic inflammation[26,27], blood lactate levels for hypoperfusion[28,29] as well as aspartate aminotransferase, alanine aminotransferase and total bilirubin levels for hepatic injury[30,31,32] using principal component analysis[33] in all 249 patients
The present study demonstrated that urinary NGAL and L-FABP were independent from each other by principal component analysis; NGAL showed linear correlations with inflammatory variables, whereas L-FABP correlated with the indicators of hypoperfusion and hepatic injury

Summary

Introduction

Integrative relationships between NGAL, L-FABP, nonrenal disorders and systemic severity of patients were investigated in the present study to determine whether the performance of these biomarkers for AKI prediction could be improved by including information on clinical context. To examine whether changes in urinary NGAL and L-FABP levels were distinct in relation to nonrenal disorders, we evaluated their relationship with C-reactive protein levels and white blood cell counts for systemic inflammation[26,27], blood lactate levels for hypoperfusion[28,29] as well as aspartate aminotransferase, alanine aminotransferase and total bilirubin levels for hepatic injury[30,31,32] using principal component analysis[33] in all 249 patients.

Results

Conclusion