Possible Relationship between Neutrophil Gelatinase-Associated Lipocalin, Hepcidin, and Inflammation in Haemodialysed Patients

Abstract

Background: Neutrophil gelatinase-associated lipocalin (NGAL) binds small, iron-carrying molecules – siderophores. On the other hand, hepcidin is a small defensin-like peptide produced by hepatocytes, modulated in response to anaemia, hypoxia, or inflammation. We tested the hypothesis that NGAL may be related to hepcidin, not only to iron metabolism, in 182 prevalent haemodialysed patients. Methods: Iron status (iron, total iron-binding capacity, ferritin, total saturation of transferrin, TSAT), complete blood count, creatinine, albumin, serum lipids were assessed using standard laboratory methods. Soluble receptor of transferrin, high-sensitivity C-reactive protein (hsCRP), tumour necrosis factor-α, interleukin-6, prohepcidin, hepcidin and NGAL were measured in serum using commercially available kits. Results: Serum NGAL, prohepcidin, hepcidin levels were significantly higher in haemodialysed patients over healthy volunteers (579.11 ± 213.95 vs. 78.43 ± 32.21 ng/ml, p < 0.001, 320.54 ± 182.65 vs. 98.65 ± 34.32 ng/ml, p < 0.01, 155.30 ± 94.05 vs. 23.65 ± 12.76 ng/ml, p < 0.001, respectively). Serum NGAL correlated strongly with residual renal function (r = –0.54, p < 0.001), Kt/V (r = 0.41, p < 0.001), hepcidin (r = –0.28, p < 0.01), serum creatinine (r = 0.63, p < 0.001), iron (r = 0.25, p < 0.01), TSAT (r = 0.30, p < 0.001), ferritin (r = 0.33, p < 0.001), hsCRP (r = 0.32, p < 0.001). In multiple regression analysis, residual renal function, hepcidin, creatinine and hsCRP were predictors of serum NGAL in haemodialysed patients. Conclusions: NGAL is highly induced in dialysed patients. NGAL could reflect both kidney function and iron metabolism. Taking into account the antimicrobial properties of NGAL, further studies are needed to address the role of NGAL in iron metabolism and inflammation in renal failure.

GDF15 Is Related to Anemia and Hepcidin in Kidney Allograft Recipients

“…The differences in the GDF15 levels in the controls may be attributed to the age, gender and even iron status. We also found a positive correlation between GDF15 and NGAL (neutrophil gelatinase-associated lipocalin), which is thought to be an acute-phase protein and marker of inflammation [28] and acute kidney injury [29]. NGAL also binds small, iron carrying molecules-siderophores.…”

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

“…Recent reports show that decreased serum NGAL levels in hemodialysis patients correlate with higher (total) hepcidin levels and lower TSAT [11,12], suggesting that low serum NGAL levels are associated with reduced iron utilization. Both CKD and CHF are chronic inflammatory conditions in which iron metabolism is disturbed.…”

“…Recently, Bolignano et al and Malyszko et al suggested that low NGAL levels in hemodialysis patients reflect reduced iron availability and transport; lower NGAL levels were associated with lower transferrin saturation (TSAT), lower ferritin levels and higher hepcidin levels [11][12][13].…”

Neutrophil Gelatinase-Associated Lipocalin and Hepcidin: What Do They Have in Common and Is There a Potential Interaction?

“…They also proposed that NGAL might be a new tool in the assessment of iron deficiency. In our recent study, we tested the hypothesis that NGAL might be related to hepcidin, not only to iron metabolism prevalent in hemodialyzed patients [47] . We found that in multiple regression analysis, residual renal function, hepcidin, creatinine and hsCRP were predictors of serum NGAL in hemodialyzed patients.…”