Neutrophil gelatinase‐associated lipocalin: pathophysiology and clinical applications

Abstract

Neutrophil gelatinase-associated lipocalin (NGAL), a 25 kDa protein produced by injured nephron epithelia, is one of the most promising new markers of renal epithelial injury. In contrast to serum creatinine and urinary output, which are measures of kidney function, NGAL is specifically induced in the damaged nephron and then released into blood and urine, where it can be readily measured. Careful proof-of-concept studies using defined animal models have uncovered the sources and trafficking of NGAL in acute kidney injury (AKI) and have addressed the contributions of renal and non-renal sources. Clinical studies indicate that NGAL, unlike creatinine, is a marker responsive to tissue stress and nephron injury, but less so to adaptive hemodynamic responses. In certain clinical settings, NGAL is an earlier marker compared with serum creatinine. In addition, clinical studies have shown that NGAL is a powerful predictor of poor clinical outcomes, which can be used to risk stratify patients when combined with serum creatinine. NGAL has important limitations, including its responsiveness in systemic inflammation, which is partially uncoupled from its response to kidney injury and which needs to be considered when interpreting NGAL results clinically. This review covers the biology and pathophysiology of NGAL and summarizes the results of the growing body of clinical studies that have addressed the utility of NGAL in the early diagnosis of AKI, in the distinction of intrinsic AKI and in the prognostic assessment of broad patient populations.

La lipocalina asociada con la gelatinasa de neutrófilos como factor temprano de predicción de la función retardada del injerto renal

“…La LAGN es producida principalmente por los neutrófilos y por las células del epitelio tubular renal (18). En estudios recientes se han encontrado diferentes clases de esta proteína: una forma monomérica de 25 kDa, un homodímero de 45 kDa y un heterodímero de 135 kDa; los neutrófilos producen el homodímero y las células tubulares renales producen los heterodímeros y monómeros (23,24). Los niveles de LAGN urinaria están compuestos por la proteína secretada por las células tubulares renales, pero también, por la producida por los neutrófilos filtrados al riñón (24).…”

“…Se cree que la LAGN induce inhibición del crecimiento bacteriano, disminución de la apoptosis y aumento de la proliferación en los túbulos renales, lo cual constituye una posible vía de protección renal (23). En los estudios en ratones con isquemia e 'injuria' por reperfusión, se encontró que al administrar LAGN recombinante por vía intraperitoneal, el daño de los tejidos renales y el número de células apoptóticas eran menores, que había un incremento en la proliferación de las células tubulares (19) y que, además, el valor de la creatinina sérica era más bajo (19), hallazgos que sugieren que la LAGN aumenta como reacción a la 'injuria' y puede desempeñar un papel importante en la recuperación renal (5,19).…”

Urinary neutrophil-gelatinase associated lipocalin is a more prognostic biomarker to distinguish antenatal hydronephrosis in neonates

“…The postnatal ultrasonography was carried out by a single independent expert radiologist blinded to the results of the Voiding cystourethrography (VCUG). VCUG was considered for the neonates at first week for patients with bilateral hydronephrosis and at [6][7][8] th week for those with unilateral forms. The reflux was graded as I to V on conventional VCUG and qualitatively as three level of mild, moderate and severe on DRNC.…”

“…NGAL, also known as lipocalin 2, involves in multiple processes such as innate immunity, apoptosis, and renal development. Accordingly, in healthy individuals, low levels of NGAL are detectable in the blood and urine (8). However, higher expression of NGAL in response to various pathological states, such as inflammation, infection, and acute kidney injury has been reported in kidney, liver and epithelial cells (9)(10).…”

Rôles des sidérophores bactériens et de mammifères dans les interactions hôtes-pathogènes

“…Elle est produite en réponse à différents stimulus physiopathologiques (inflammation, intoxication, infection, ischémie, transformation néoplasique). Chez l'homme, la protéine est détectée dans le sang et à un faible niveau dans les urines, étant filtrée par le glomérule et réabsorbée dans le tube proximal du rein [27]. SYNTHÈSE REVUES en fer repose essentiellement sur des sidérophores de type catécholate comme l'entérobactine d'E.…”