Biological or Clinical Significance:
NGAL (neutrophil gelatinase-associated lipocalin; also called lipocalin 2, siderocalin and 24p3) belongs to the lipocalin family of proteins. These are typically small secreted proteins characterized by their ability to bind small, hydrophobic molecules in a structurally conserved pocket formed by a β-pleated sheet, to bind to specific cell-surface receptors and to form macromolecular complexes. Because of its small molecular size and resistance to degradation, NGAL is readily excreted and detected in the urine, both in its free form and in complex with MMP-9. Urinary levels correlate with plasma or serum levels whatever the cause of increased NGAL production but particularly high urinary levels can be expected when it is released directly into the urine by the kidney tubules or urothelial carcinomas. While the functions of NGAL are not fully understood, it appears to be upregulated in cells under “stress”, e.g. from infection, inflammation, ischemia or neoplastic transformation, or in tissues undergoing involution. It may have an antibacterial role, as shown by its binding enterobactin and other siderophores, depriving the microorganisms of Fe3+, an important microbial nutritional requirement. Even before NGAL had been isolated from human neutrophils, its mouse homologue was known to be expressed by kidney cells and to undergo an early, dramatic upregulation in response to viral infection. Similar early and dramatic upregulation was observed in rat proximal tubule cells after ischemia-reperfusion injury. In humans, elevated plasma levels of NGAL have been found to be strongly correlated with decreased renal function in patients with systemic vasculitis. The results for renal ischemia-reperfusion injury were subsequently extended to nephrotoxic agents. Elevated urinary and serum NGAL levels have also been observed in patients with established renal failure and patients with functioning renal grafts. Thus, a large variety of renal disorders appear to be associated with increased plasma and urinary levels of NGAL. While plasma and urinary NGAL levels are closely correlated in acute conditions, it is to be expected that urinary NGAL levels will be particularly high after ischemic renal injury severe enough to result in acute renal failure, acute tubular necrosis or acute tubulo-interstitial nephropathy.
Principle of Test Method:
The NGAL assay is a solid-phase ELISA that employs the quantitative sandwich enzyme immunoassay principle.
*Stability given for sample with stabilizer added upon collection.
**Long term stability study in process; please contact nexelis for stability information.