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-alpha, 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.