Serum Hepcidin Levels Are Associated With Serum Triglycerides and Interleukin‐6 Concentrations in Patients With End‐Stage Renal Disease

Abstract

Hepcidin has emerged as a peptide with a key role in the regulation of iron homeostasis in patients with chronic kidney disease (CKD), having a strong dependence on inflammation. Recent studies reveal that hepcidin may be also associated with the progression of atherosclerosis. This study was performed to analyze the relation of hepcidin to markers of atherosclerosis and inflammation in patients on dialysis. A total of 90 individuals were enrolled. Sixty patients with end-stage renal disease, who were on hemodialysis (HD) (N = 30) and peritoneal dialysis (N = 30) were compared with 30 normal controls (NC). Age, body mass index, time on dialysis, serum lipids, C-reactive protein (CRP) and interleukin-6 (IL-6) were measured and analyzed in correlation with hepcidin concentration. It was found that patients on HD and peritoneal dialysis have significantly higher (P < 0.0001) levels of hepcidin, CRP and IL-6 than NC. Hepcidin in dialysis patients is significantly related to age (r = 0.373, P = 0.012), serum triglycerides (r = 0.401, P = 0.005), HDL-C (r = -0.268, P = 0.048), CRP (r = 0.436, P = 0.0007) and IL-6 (r = 0.569, P < 0.0001). In multiple regression analysis, hepcidin correlated independently with triglycerides (β = 0.402, P = 0.041) and IL-6 (β = 0.559, P = 0.006). Moreover, patients with high triglycerides in combination with high IL-6 levels have significantly increased concentrations of hepcidin than those with low triglycerides and low IL-6 levels (P < 0.0001). Elevated levels of hepcidin in patients with CKD on dialysis may be related to the occurrence of high triglycerides and high IL-6 serum concentrations. This probably suggests that hepcidin may play a role to the progression of atherosclerosis and inflammation, but this hypothesis should be further evaluated.

Relationship between serum hepcidin levels and cardiovascular disease in patients with maintenance hemodialysis

“…Results of this study are consistent with the previous research [26]. Additionally, there is a positive correlation between serum hepcidin and hsCRP and IL-6 in MHD patients, indicating that the increase of serum hepcidin in MHD patients is related to the state of inflammation, as reported in a previous study [27]. Some studies have shown that IL-6 can regulate the expression of the hepcidin gene by the following mechanism: IL-6 can activate the transcription activator of ferritin by combining with signal transduction and transcription activator 3 (STAT3), thereby increasing the synthesis of hepcidin [28,29].…”

Prepregnancy Body Mass Index and Gestational Weight Gain Have No Negative Impact on Maternal or Neonatal Iron Status

“…However, neither IL-6 nor leptin was correlated with hepcidin during pregnancy. Positive correlations between IL-6 and hepcidin have been reported in patients with end-stage renal disease 37 and sepsis 38 but not in healthy premenopausal 11 or pregnant women. 5,32 The absence of positive relationships in individuals without severe inflammation may suggest that a threshold level of IL-6 must be reached to significantly impact hepcidin production.…”

Optimal Serum Ferritin Levels for Iron Deficiency Anemia during Oral Iron Therapy (OIT) in Japanese Hemodialysis Patients with Minor Inflammation and Benefit of Intravenous Iron Therapy for OIT-Nonresponders

“…Our study confirmed our previous finding that ferritin and hepcidin-25 could be predictive factors for the response to OIT in HD patients in the absence of inflammation [ 25 ]. Serum levels of hepcidin-25 were positively correlated with triglycerides and interleukin (IL-6) and CRP in HD patients [ 47 , 48 ]. In addition, high serum levels of triglycerides were associated with hyporesponsiveness to IIT in HD patients [ 19 ].…”

“…These factors can increase ferritin and hepcidin-25, leading to reduced iron availability for erythropoiesis [ 39 ]. In fact, serum levels of IL-6 were correlated with those of ferritin and hepcidin-25 in CKD patients [ 17 , 46 , 48 ]. Regardless of ferritin and inflammation markers (CRP and IL-6), the levels of anti-oxidant glutathione peroxidase in erythrocytes were lower in the IIT-nonresponders than in the IIT-responders [ 52 ].…”