Renal neutrophil gelatinase associated lipocalin expression in lipopolysaccharide-induced acute kidney injury in the rat

BACKGROUND Neutrophil 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. METHODS To 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. RESULTS Renal 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). CONCLUSIONS NGAL 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.