Hepcidin, an acute-phase protein and a marker of inflammation in kidney transplant recipients with and without coronary artery disease

Abstract

Background: In kidney transplant recipients, endothelial dysfunction and atherosclerosis are almost universal, as are cardiovascular complications. Inflammatory markers have been shown to play a role in the pathogenesis and progression of atherosclerosis, regarded as a chronic inflammatory condition. Iron metabolism is disturbed in chronic inflammatory diseases such as atherosclerosis. Hepcidin, the liver-expressed antimicrobial peptide, LEAP-1, is an acute-phase reactant produced in the liver that displays intrinsic antimicrobial activity. Cross-sectional study was performed to assess possible relations between hepcidin and inflammatory markers in kidney transplant recipients with versus without coronary artery disease (CAD).

Methods: Iron status, complete blood count, creatinine, albumin, and lipids were estimated using standard laboratory methods. Glomerular filtration rate (GFR) was calculated using the MDRD formula. Hepcidin, high-sensitivity C-reactive protein (CRP), IL-6, TNFalpha, and soluble receptor of transferrin were measured using commercially available kits.

Results: Kidney transplant recipients with CAD were older, and showed higher hepcidin, hsCRP, IL-6, TNFalpha, sTFR, ferritin, and lower cholesterol levels than did patients without CAD. Univariate analysis of values in kidney transplant recipients showed hepcidin to correlate significantly with total protein, ferritin, time after transplantation, creatinine, eGFR (simplified MDRD), cholesterol, neutrophil count, hsCRP, and IL-6. There were tendencies to correlate with TNFalpha. Multiple regression analysis showed that hepcidin was independently related to GFR, cholesterol, and hsCRP.

Conclusions: Elevated hepcidin values in kidney allograft recipients may be due not only to impaired renal function, but also to a low-grade inflammatory state, as reflected by hepcidin correlations with hsCRP, IL-6, and ferritin.