Neutrophil gelatinase-associated lipocalin: ready for routine clinical use? An international perspective

Abstract

Acute kidney injury (AKI) remains a challenge in terms of diagnosis and classification, its morbidity and mortality remaining high in the face of improving clinical protocols. Current clinical criteria use serum creatinine (sCr) and urine output to classify patients. Ongoing research has identified novel biomarkers that may improve the speed and accuracy of patient evaluation and prognostication, yet the route from basic science to clinical practice remains poorly paved. International evidence supporting the use of plasma neutrophil gelatinase-associated lipocalin (NGAL) as a valuable biomarker of AKI and chronic kidney disease (CKD) for a number of clinical scenarios was presented at the 31st International Vicenza Course on Critical Care Nephrology, and these data are detailed in this review. NGAL was shown to be highly useful alongside sCr, urinary output, and other biomarkers in assessing kidney injury; in patient stratification and continuous renal replacement therapy (CRRT) selection in paediatric AKI; in assessing kidney injury in conjunction with sCr in sepsis; in guiding resuscitation protocols in conjunction with brain natriuretic peptide in burn patients; as an early biomarker of delayed graft function and calcineurin inhibitor nephrotoxicity in kidney transplantation from extended criteria donors; as a biomarker of cardiovascular disease and heart failure, and in guiding CRRT selection in the intensive care unit and emergency department. While some applications require further clarification by way of larger randomised controlled trials, NGAL nevertheless demonstrates promise as an independent biological marker with the potential to improve earlier diagnosis and better assessment of risk groups in AKI and CKD. This is a critical element in formulating quick and accurate decisions for individual patients, both in acute scenarios and in long-term care, in order to improve patient prognostics and outcomes.

Fig. 1

Relative differences between urinary NGAL commercial assays [4]. Each symbol represents a different commercial NGAL assay.

Fig. 2

Fluid overload and mortality in children receiving CRRT: The Prospective Paediatric Continuous Renal Replacement Therapy Registry [8].

Fig. 3

Outline of Taking Focus study protocol [7].

Fig. 4

Plasma NGAL concentrations according to the PCT groups were 95 (16–129) ng/ml, 149 (19–1,300) ng/ml, 245 (33–1,300) ng/ml, 605 (55–1,300) ng/ml, and 462 (127–1,300) ng/ml, respectively. Septic patient groups (groups III–V, as dictated by PCT concentrations) displayed median plasma NGAL concentrations above the medical decision point of 150 ng/ml [11].

Fig. 5

Plasma NGAL was significantly higher in septic patients (groups III–V) than in non-septic patients (groups I and II) (337.5 vs. 129.0 mg/ml, p < 0.0001) [11].

Fig. 6

Comparison of BNP and NGAL concentrations between the compartment syndrome cohort (CS, n = 5) and controls (C, n = 10).

Fig. 7

Incidence of DGF in kidney transplantation over the last years (data from the ‘A. Vercellone’ Kidney Transplantation Center, University of Torino).

Fig. 8

Plasma NGAL levels 24 h following kidney transplantation from ECDs. DGF was associated with significantly higher levels of NGAL compared with non-DGF group (n = 25). Plasma NGAL levels >400 ng/ml seem to be predictive of DGF (data from the ‘A. Vercellone’ Kidney Transplantation Center, University of Torino).

Fig. 9

Multivariate Cox proportional hazards model for risk of death or CVD per 1 SD increase in log₁₀ NGAL and other biomarkers, indicating that NGAL is an independent predictor of outcome. Steps: (1) age, sex; (2) previous step + DM, HTN, smoking, SBP, chol, HDL, CrCl, BMI; (3) previous steps + NT-proBNP, CRP [37]. ^aCombined cardiovascular endpoint is coronary revascularization, myocardial infarction, or CVD death; ^bvalues are significant at p < 0.001; ^cvalues are significant at p = 0.001.

Fig. 10

Meta-analysis of WRF, indicating an association with poor clinical outcome [unpubl. data].

Fig. 11

Long-term follow-up of eGFR and NGAL levels, indicating that NGAL is predictive of WRF [unpubl. data].

Fig. 12

Plasma NGAL concentrations could be integrated into clinical decision-making by helping to stratify risk groups in patients, thereby aiding patient selection for treatments such as RRT [55, 56].

Fig. 13

Outline of the multicentre prospective emergency department study investigating the sensitivity of NGAL as an additional biomarker to Cr in early risk evaluation of AKI [58].