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

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.

Rosiglitazone Did Not Induce Acute Kidney Injury in Normocholesterolemic Rats Despite Reduction in Glomerular Filtration Rate

“…Our results confirm current information that diuresis and sodium excretion have not been considered as good biomarkers for the diagnosis of AKI [26]. Indeed, uNGAL levels reflect better AKI as shown by Han et al in rats with sepsis [27]. …”

Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Chronic Cardiorenal Failure is Correlated with Endogenous Erythropoietin Levels and Decreases in Response to Low-Dose Erythropoietin Treatment

“…A possible explanation for our findings is that in our population serum NGAL is a marker of on-going tubular damage. This finding is in agreement with studies showing that NGAL predominantly reflects tubular damage in acute conditions [25,26]. A comparable association was already explored about ten years ago for IgA nephropathy; urinary N-acetyl-β-D-glucosaminidase (NAG), a marker of tubular injury, correlated with EPO levels [27].…”

Usefulness of urinary biomarkers for nephrotoxicity in cynomolgus monkeys treated with gentamicin, cisplatin, and puromycin aminonucleoside

“…The usefulness of NGAL to detect the damage of the renal tubules has been reported in rats (Han et al, 2012;Phillips et al, 2016) and dogs (Kai et al, 2013;Zhou et al, 2014). After renal ischemia or nephrotoxicity, intrarenal NAGL synthesis is dramatically upregulated at protein levels.…”