The control group consisted of 30 healthy volunteers. Serum HJV, hepcidin, ferritin, IL-6, hsCRP, and serum creatinine were significantly higher (allP< 0.001), whereas serum iron, sTFR, transferrin, hemoglobin, and erythrocyte count were significantly lower in HD patients, compared to healthy volunteers (allP< 0.001). In univariate analysis, HJV was strongly correlated (P< 0.001) with ferritin, transferrin saturation, and TIBC, as well as with hsCRP, hepcidin, Kt/V (P< 0.01) and residual renal function, the presence of diabetes, APKD, and coronary heart disease. Predictors of HJV level in multiple regression analysis were ferritin (beta value was 0.50,P= 0.00004) and transferrin saturation (beta value was 0.47,P= 0.0002), explaining 81% of the HJV variations. == Conclusions == Serum HJV is usually elevated in HD patients and related predominantly to kidney function and iron metabolism. However, HJV is probably not correlated to inflammation. HJV appears to be a new player in iron metabolism in these patients. Keywords:Iron metabolism, Hemodialysis, Inflammation, Hepcidin, Hemojuvelin == Introduction == Hemojuvelin (HJV) is usually a membrane protein that is Pralidoxime Iodide responsible for an iron overload condition known as juvenile hemochromatosis [1]. HJV is usually highly expressed in the liver, skeletal muscles, and heart [2]; it seems to play a role in iron absorption and release from cells and also has anti-inflammatory properties [3]. One feature of the pathogenesis of juvenile hemochromatosis is usually that patients have low to undetectable urinary hepcidin levels, suggesting that HJV is usually a positive regulator of hepcidin, the central iron regulatory hormone. As a result, low hepcidin levels result in increased intestinal iron absorption. Moreover, HJV plays an essential role in the regulation of hepcidin expression, specifically in the iron-sensing pathway [4]. Hepcidin has recently emerged as a key regulator of iron homeostasis [5]. Hepcidin is usually a small defensin-like peptide produced by the hepatocytes. Its production is usually modified in response to anemia, hypoxia, and inflammation [6]. Stimulation by IL-6 is necessary for hepcidin synthesis during inflammation (the IL-6-hepcidin axis), but not for hepcidin activation during iron overload [7]. According to Niederkofler et al. [4], dietary iron-sensing and inflammatory pathways converge in the regulation of hepcidin, but how these two pathways intersect remains unclear. Hepcidin was found to be elevated in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) undergoing renal replacement therapy [8,9]. Moreover, in the first studies, relations between prohepcidin and anemia were described [10,11]. There are no data available on HJV levels in CKD; however, the mean soluble HJV concentration in patients with anemia of chronic disease was reported to be significantly higher than in controls [12]. This study was performed to test for the first time the hypothesis that HJV is related to iron metabolism in HD patients and also to assess the correlation between HJV and hepcidin and other markers of inflammation. == Patients and methods == == Study population == The study included 110 prevalent patients on maintenance HD. Inclusion criteria were: Pralidoxime Iodide a stable clinical state, no thrombosis or inflammation (serum CRP below 6 mg/l using a Pralidoxime Iodide semiquantitative method), and absence of acute cardiovascular complications (including uncontrolled hypertension, acute coronary syndrome, and acute heart failure). Patients with renal graft failure and/or on immunosuppressive therapy were excluded. The control group consisted of 30 healthy volunteers. All patients were fully informed about the study and gave their consent. The study was approved by the local Medical University Ethics Committee. Rabbit Polyclonal to SNX3 == Laboratory measurements == Blood was drawn in all patients in the morning between 8.00 am. and 9.00 am. before the onset of the midweek dialysis session and before heparin administration. Blood for urea and creatinine measurements for Kt/V calculation was taken after hemodialysis from the arterial line of the hemodialysis system, immediately before discontinuation of the extracorporeal circulation. Enoxaparin (Clexane, Aventis) was used as an anticoagulant during hemodialysis and was given as a single intravenous injection at the beginning of each dialysis session. The blood drawn from the patients was centrifuged at 2500gfor 15 min at room temperature to serum. Samples were aliquotted and stored at 40C before assays. High-sensitivity CRP was studied using kits from American Diagnostica, Greenwich, CT, USA. Soluble transferring receptor (sTfR) and interleukin-6 (high sensitivity) and TNF (high sensitivity) were studied using kits from R&D (Abington, UK). Hepcidin was measured by an assay from Bachem, UK. HJV was assessed using commercially available kit from uscnb.life, China. Hemoglobin, total protein, serum lipids, albumin, CRP (for screening purposes, using a semiquantitative method in which.