NGAL Biomarker

How does NGAL compare to serum creatinine?

Neutrophil gelatinase-associated lipocalin (NGAL) is a biomarker of renal injury that can be detected in urine and plasma as early as 2 hours after injury.ⁱ Expressed in proximal and distal nephron tubules, it is one of the most upregulated genes and over-expressed proteins in the kidney following ischemic or nephrotoxic injury. It is not filtered by the kidney, and therefore, elevations in NGAL directly correlate with kidney damage, not functional impairment.ⁱ 

In contrast, serum creatinine (SCr) is a product of muscle breakdown that can be impacted by nonrenal factors including age, nutrition and muscle mass. It is an indirect measure of kidney function and takes 48-72 hours to respond to kidney injury. It is estimated that 50% of kidney function must be lost before serum creatinine rises. Elevations in SCr may not always reflect kidney injury and subclinical AKI may occur without a rise in SCr.ⁱⁱ

How quickly does the NGAL biomarker rise after injury?

NGAL is a rapid response biomarker that can be detected in both urine and plasma that increases as early as 2 hours after injury.ⁱ Early identification of AKI, with an injury biomarker like NGAL, may provide more time for targeted intervention and management before permanent kidney damage occurs.ⁱ

Is NGAL a reliable diagnostic marker?

NGAL shows strong evidence as an early biomarker of acute kidney injury (AKI), rising in urine and plasma ahead of serum creatinineⁱ. However, NGAL should be used adjunctively, and not as a standalone diagnostic, as spikes in NGAL level are not caused by AKI alone.

What is the function of NGAL?

NGAL (also known as lipocalin‐2) is a ~25 kDa protein produced by neutrophils, renal tubular cells, and others in response to stress or inflammationⁱⁱ. Functionally, it binds bacterial siderophores to sequester iron and limit microbial growth (an innate immune role)ⁱⁱ. In the kidney, it is upregulated after tubular injury and may participate in epithelial repair/regeneration and iron trafficking within injured tissueⁱⁱ. 

References

ⁱ Devarajan P. Neutrophil gelatinase-associated lipocalin: a promising biomarker for human acute kidney injury. Biomark Med. 2010;4(2):265–280.

ⁱⁱMoledina DG, Parikh CR. Phenotyping of Acute Kidney Injury: Beyond Serum Creatinine. Semin Nephrol. 2018;38(1):3-11.

ⁱ Devarajan P. Neutrophil gelatinase-associated lipocalin: a promising biomarker for human acute kidney injury. Biomark Med. 2010;4(2):265–280.

ⁱⁱMurray PT, Mehta RL, Shaw A, et al. Potential use of biomarkers in acute kidney injury report and summary of recommendations from the 10th Acute Dialysis Quality Initiative consensus conference. Kidney Int. 2014.85(3):513-521

ⁱⁱⁱStanski N, Menon S, Goldstein SL, Basu RJ. Integration of urinary neutrophil gelatinase-associated lipocalin with serum creatinine delineates acute kidney injury phenotypes in critically ill children. Journal Critical Care. 2019.53:1-7.

^ivKrawczeski CD, Goldstein SL, Woo JG, et al. Temporal relationship and predictive value of urinary acute kidney injury biomarkers after pediatric cardiopulmonary bypass. J Am Coll Cardiol. 2011;58(22):2301–2309.

^vHaase M, Devarajan P, Haase-Fielitz A, et al. The outcome of neutrophil gelatinase-associated lipocalin-positive subclinical acute kidney injury: a multicenter pooled analysis of prospective studies. J Am Coll Cardiol. 2011;57(17):1752–1761.

^viZappitelli M, Washburn KK, Arikan AA, et al. Urine neutrophil gelatinase-associated lipocalin is an early marker of acute kidney injury in critically ill children: a prospective cohort study. Crit Care. 2007;11(4):R84.

^viiVarnell CD Jr, Goldstein SL, Devarajan P, Basu RK. Impact of Near Real-Time Urine Neutrophil Gelatinase-Associated Lipocalin Assessment on Clinical Practice. Kidney Int Rep. 2017 Jun 3;2(6):1243-1249.

^viiiHaase-Fielitz A, Haase M, Devarajan P. Neutrophil gelatinase-associated lipocalin as a biomarker of acute kidney injury: a critical evaluation of current status. Ann Clin Biochem. 2014;51(Pt 3):335–351.