NGAL as a Marker of Renal Tubular Injury
Neutrophil gelatinase-associated lipocalin (NGAL) is primarily a marker of the renal tubules, specifically the distal tubule and collecting duct, where it is produced and released following tubular epithelial injury. 1, 2, 3
Anatomical Source and Production
NGAL is produced by injured nephron epithelia, particularly in the distal tubular segments, making it a sensitive biomarker for acute tubular damage rather than glomerular injury 3
The protein is a 25-kDa molecule that is specifically induced in damaged nephron tissue and subsequently released into both blood and urine where it can be readily measured 3, 4
NGAL is both filtered by the glomerulus and directly secreted by tubular cells, with the distal tubule being the primary renal source during kidney injury 5, 3
Important Caveat: Extra-Renal Sources
Recent evidence demonstrates that hepatocytes are actually the primary source of plasma and urine NGAL during acute kidney injury, mediated by IL-6 signaling, which fundamentally changes how NGAL should be interpreted 6
During AKI, IL-6 stimulates hepatic NGAL production, and this hepatocyte-derived NGAL appears in urine specifically during proximal tubule dysfunction when the tubules cannot properly reabsorb filtered proteins 6
While NGAL was traditionally considered a tubule-specific injury marker, it is also produced by neutrophils, macrophages, and dendritic cells in response to systemic inflammation, which can confound its interpretation 4
Clinical Interpretation
NGAL reflects both structural tubular injury and functional changes in glomerular filtration, making it unique among AKI biomarkers but requiring careful interpretation in the clinical context 5
The combination of functional biomarkers (like cystatin C) with damage biomarkers (like NGAL) is superior to creatinine alone for predicting AKI severity and persistence 2
NGAL can help differentiate acute tubular necrosis from functional kidney injury (such as hepatorenal syndrome) in patients with cirrhosis, as it specifically indicates tubular damage 1, 2