Abstract
BackgroundNeutrophil gelatinase associated lipocalin (NGAL) is a highly predictive biomarker of acute kidney injury. To understand the role of NGAL in renal injury during sepsis, we investigated the temporal changes and biological sources of NGAL in a rat model of acute kidney injury, and explored the relationship between renal inflammation, humoral NGAL and NGAL expression during endotoxemia.MethodsTo induce acute renal injury, rats were treated with lipopolysaccharide (LPS, 3.5 mg/kg, ip), and the location of NGAL mRNA was evaluated by in situ hybridization. Quantitative RT-PCR was also used to determine the dynamic changes in NGAL, tumor necrosis factor α (TNFα) and interleukin (IL)-6 mRNA expression 1, 3, 6, 12, and 24 hours following LPS treatment. The correlation among NGAL, TNFα and IL-6 was analyzed. Urinary and plasma NGAL (u/pNGAL) levels were measured, and the relationship between humoral NGAL and NGAL expression in the kidney was investigated.ResultsRenal function was affected 3–12 hours after LPS. NGAL mRNA was significantly upregulated in tubular epithelia at the same time (P < 0.001). The course of NGAL mRNA upregulation occurred in parallel with renal damage. There was a transient increase in TNFα and IL-6 mRNA levels within 3 hours following LPS administration, and a strong correlation between TNFα and NGAL mRNA (r = 0.995, P <0.001) but not with IL-6 mRNA. Both pNGAL and uNGAL levels were markedly increased compared with those in the control group (P < 0.001); however, only uNGAL levels were correlated with NGAL mRNA (r = 0.850, P <0.001).ConclusionsNGAL upregulation is sensitive to LPS-induced renal TNFα increase and injury, which are observed in the tubular epithelia. Urinary NGAL levels accurately reflect changes in NGAL in the kidney.
Highlights
Neutrophil gelatinase associated lipocalin (NGAL) is a highly predictive biomarker of acute kidney injury
Shapiro et al assessed the diagnostic accuracy of plasma NGAL (pNGAL) in predicting Acute kidney injury (AKI), wherein it was revealed that pNGAL concentrations of >150 ng/mL were 96 % sensitive but only 51 % specific for patients with suspected septic AKI[9]
Martensson et al observed that pNGAL is elevated in patients with systemic inflammatory response syndrome, severe sepsis, and septic shock, and it should be used with caution as a marker of AKI in intensive care unit (ICU) patients with septic shock [10]
Summary
Neutrophil gelatinase associated lipocalin (NGAL) is a highly predictive biomarker of acute kidney injury. Acute kidney injury (AKI; or acute renal failure) is an important issue for patients during critical care, with sepsis being the most common trigger for AKI in the intensive care unit (ICU) [1,2,3]. In previous research of critically ill patients [8,9], both serum NGAL (sNGAL) and plasma NGAL (pNGAL) levels have the potential to act as early biomarkers for AKI. While both of them are highly sensitive, they have not been found to be very specific predictors of septic AKI. Understanding the role of NGAL in impaired renal tissues may help clarify this issue
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