Hepcidin Levels Research Articles

Sevuparin strongly reduces hepcidin expression in cells, mice, and healthy human volunteers.

Hepcidin is an essential regulator of systemic iron availability mediating both iron uptake from the diet and its release from body stores. Abnormally high hepcidin levels resulting from inflammation in chronic diseases cause iron restriction with the onset of anemia. Restoring physiological levels of hepcidin could contribute to ameliorating anemia in these patients. Heparin derivatives are known to suppress hepcidin expression acting on the BMP/SMAD pathway. The novel heparin derivative sevuparin, modified to markedly reduce its anticoagulant activity, is proposed as a promising hepcidin antagonizing strategy. Sevuparin was tested for its anti-hepcidin properties in vitro in HepG2 cells, in vivo in mice, and in healthy volunteers. Sevuparin strongly suppressed basal, BMP6-, and IL6-dependent hepcidin expression in HepG2 cells in a dose- and time-dependent manner, modulating the essential BMP6/SMAD cascade. These effects were evident in C57BL/6J mice after intravenous injection of a single dose of sevuparin (20 mg/kg) with a 70% reduction of hepcidin mRNA. Remarkably, similar effects were observed in healthy volunteers following single subcutaneous doses at 3, 6, and 9 mg/kg with 40%-50% suppression at 3 and 6 mg/kg and 72% at 9 mg/kg. Moreover, sevuparin was able to reduce hepcidin upregulation in a mouse model of acute inflammation induced by LPS, also showing an amelioration of the inflammatory markers. Combined with its excellent safety profile, these data suggest a role for sevuparin in treating high-hepcidin disorders.

Circulating Hepcidin Levels Are an Independent Predictor of Survival in Microsatellite Stable Metastatic Colorectal Cancer Patient Candidates for Standard First-Line Treatment

Background & Aim. Hepcidin, a key hormone in iron homeostasis, is synthesized by colorectal cancer (CRC) cells, particularly in the late stages of tumorigenesis. This study aimed to ascertain whether the serum levels of hepcidin could serve as a prognostic biomarker in microsatellite stable (MSS) metastatic CRC (mCRC). Specifically, we assessed the predictive value of baseline serum hepcidin levels for the overall survival (OS) of patients with MSS mCRC receiving first-line treatment with FOLFOX-panitumumab (RAS/BRAF wild-type) or FOLFOX-bevacizumab (RAS or BRAF mutations). Methods. Serum samples were prospectively collected from 35 normal healthy volunteers (normal controls) and 55 patients with MSS mCRC and analyzed for their content of hepcidin by ELISA. Results. Serum hepcidin levels were significantly greater in patients with mCRC than in the normal controls. In the mCRC group, patients with baseline levels of hepcidin greater than 40 ng/mL had a significantly shorter 1-year OS rate (39%) than those with hepcidin levels lower than 40 ng/mL (80%) [hazard ratio (HR): 2.94; 95% CI: 1.27–6.84; p = 0.01]. A multivariate Cox regression analysis showed that the pre-treatment serum hepcidin levels were an independent prognostic factor for OS, not influenced by other well-known prognostic factors (i.e., CEA status, Karnofsky performance score, number of metastatic sites, RAS/BRAF mutations), and this was evident across all major patient subgroups. Conclusions. Our data show that baseline serum levels of hepcidin are an independent risk factor for OS in MSS mCRC patients undergoing standard first-line treatment. Further prospective and extensive studies are needed to confirm and validate our findings.

Recurrent BMP4 variants in exon 4 cause non-HFE-associated hemochromatosis via the BMP/SMAD signaling pathway

BackgroundHereditary hemochromatosis (HH) is an iron overload disorder and can be caused by variants in non-HFE genes in Chinese patients. However, there is still a considerable proportion of patients suffering from unexplained iron overload. In our previous study, we had identified the p.R269Q variant in exon 4 of the Bone morphogenetic protein 4 (BMP4) gene in Chinese patients with unexplained primary iron overload by Whole Exome sequencing, and then the BMP4 p.H251Y variant was identified by Sanger sequencing in a Chinese patient with secondary iron overload. Our study aimed to explore the pathogenicity and underlying mechanism of BMP4 p.H251Y and BMP4 p.R269Q variants in patients with iron overload.MethodsSanger sequencing was conducted to identify the novel variants in the BMP4 gene of patients with unexplained iron overload. MRI and liver biopsy were used to display iron overload in the liver of the patient harboring the BMP4 p.H251Y variant. The BMP4 and hepcidin levels in BMP4 knockdown and BMP4 variant cells were examined by enzyme-linked immunosorbent assay. The effects of BMP4 p.H251Y and BMP4 p.R269Q variants on the hepcidin-regulation pathway were studied.ResultsOne of 54 HH patients (1.85%) harbored the BMP4 p.R269Q variant. One of 148 patients (0.68%) with secondary hemochromatosis harbored the BMP4 p.H251Y variant, and these two variants were not found in 100 Chinese general population. For the patient harboring the BMP4 p.H251Y variant, abdominal MRI and Perl's staining of liver tissue displayed iron overload in the liver. Cells transfected with the BMP4 p.H251Y and p.R269Q variants showed down-regulation of hepcidin level and BMP/SMAD pathway compared with cells transfected with the wild-type BMP4 vector.ConclusionThe BMP4 p.H251Y and p.R269Q variants can downregulate hepcidin levels by inhibiting the BMP/SMAD axis, suggesting they may play pathogenic roles in iron overload.

Hepcidin agonists grape seed proanthocyanidins and berberine hydrochloride improve immunity and prevention against bacterial infection in grass carp (Ctenopharyngodon idella)

Hepcidin is an antimicrobial peptide and iron-regulating factor that has been shown to play a crucial role in combating bacterial diseases, making it a viable alternative to antibiotics. However, its widespread application is limited due to its susceptibility to degradation in vivo and high production costs. Certain extracts from traditional Chinese medicinal plants exhibit significant potential in treating iron overload conditions. This study aims to identify an effective and practical herbal agent as a hepcidin agonist. The results indicated that grape seed proanthocyanidins (GSP) and berberine hydrochloride (BBR) significantly upregulate the expression levels of hepcidin and ferritin genes in L8824 cells. Additionally, both compounds exhibited excellent in vitro antibacterial activity. Interestingly, the combined application of these two substances yields unexpectedly favorable results. Oral administration of GSP + BBR effectively promoted growth in grass carp, enhanced survival rates, and significantly increased serum innate immunity indicators. Furthermore, it reduced bacterial loads in the head kidney, spleen, hepatopancreas, and intestinal of grass carp following infection. Additionally, it elevated the expression levels of immune genes IL-1β, IL-6, and TNF-α in the head kidney after infection, and markedly alleviated pathological damage in intestinal tissues. These results demonstrated that GSP and BBR act as hepcidin agonists to enhance the expression of endogenous hepcidin, providing a novel approach for the prevention of bacterial infections in aquaculture.

Could Hepcidin Be a New Biomarker in Patients with Idiopathic Pulmonary Fibrosis (IPF)?

Objectives: Hepcidin is a biomarker produced by hepatocytes in chronic disease anemia and is known to increase during chronic inflammation. This study compares the hepcidin levels in idiopathic pulmonary fibrosis (IPF) patients and controls, evaluating its relationship with anemia and systemic inflammation in IPF patients. Methods: This study included 82 IPF patients and 31 controls. Hepcidin levels were compared between the two groups. In the IPF group, the hepcidin and anemia parameters were compared between anemic and non-anemic patients. The significance between the hepcidin and systemic inflammation parameters such as Erythrocyte Sedimentation Rate, CRP (C-reactive protein) levels, ferritin levels, and the Systemic Immune-Inflammation Index (SII) was investigated. Erythrocyte Sedimentation Rate, C-reactive protein (CRP) levels, and ferritin levels were measured using automated analyzers. Hepcidin and erythropoietin (EPO) levels were determined using ELISA kits. Results: A significant difference in hepcidin levels was found between the IPF and control groups (37.13 ± 14.92 vs. 25.77 ± 11.25, p < 0.001). No significant difference in hepcidin levels was found between anemic and non-anemic IPF patients (38.25 ± 16.2 vs. 36.7 ± 14.6, p = 0.719). No significant correlation was found between hepcidin levels and anemia parameters (serum iron, ferritin, vitamin B12, serum transferrin, transferrin saturation, total iron-binding capacity, hemoglobin, folate, and erythropoietin) in IPF patients. Despite significant differences in the systemic inflammation parameters (ferritin and CRP) between patients and controls, no significant correlation was found between their hepcidin and systemic inflammation parameters. Conclusions: Our study demonstrates that the hepcidin levels in IPF patients are elevated independently of anemia and systemic inflammation. We propose that hepcidin could be a potential biomarker to be investigated in IPF patients.

Alterations of Hepcidin and Iron Markers Associated with Obesity and Obesity-related Diabetes in Gambian Women

Aims Obesity, type 2 diabetes (T2D), and chronic inflammation are associated with disturbances in iron metabolism. Hepcidin is hypothesized to play a role in these alterations owing to its strong association with inflammation via the JAK-STAT3 pathway. The current study investigated the differences between inflammatory markers and iron indices and their association with hepcidin in lean women, women with obesity, and women with obesity and T2D (obesity-T2D) in The Gambia. Materials and methods In a cross-sectional study design, fasted blood samples were collected from three groups of women: lean women (n=42, body mass index (BMI)=20.9 kg/m2), women with obesity (n=48, BMI=33.1 kg/m2) and women with obesity-T2D (n=30, BMI=34.5 kg/m2). Markers of inflammation (IL-6 and CRP) and iron metabolism [hepcidin, iron, ferritin, soluble transferrin receptor (sTfR), transferrin, transferrin saturation, and unsaturated iron-binding capacity (UIBC)] were compared using linear regression models. Simple regression analyses were performed to assess the association between hepcidin levels and respective markers. Results Women with obesity and obesity-T2D showed elevated levels of inflammatory markers. There was no evidence that markers of iron metabolism differed between lean women and obese women, but women with obesity-T2D had higher transferrin saturation, higher serum iron concentration, and lower UIBC. Serum hepcidin concentrations were similar in all the groups. Hepcidin was not associated with markers of inflammation but was strongly associated with all other iron indices (all P&lt;0.002). Conclusion Contrary to our original hypothesis, hepcidin was not associated with markers of inflammation in the three groups of Gambian women, despite the presence of chronic inflammation in women with obesity and obesity-T2D.

Hepcidin levels in Mexican pregnant women without family preeclampsia

Hepcidin levels in Mexican pregnant women without family preeclampsia

Obesity and iron deficiency: what is the connection and how to treat?

The article presents a review of the literature and our own data on the etiology and pathogenesis of iron deficiency and iron deficiency anemia in patients with obesity. Obesity is considered as a subclinical systemic chronic inflammation, which is associated with an increase in the level of hepcidin, which is a key mediator of anemia during inflammation. Patients with obesity should undergo periodic screening of iron status and ferrokinetic parameters. Today, new oral iron preparations with increased tolerability and improved absorption are used in clinical practice. These include sucrosomial iron preparations. Sucrosomial iron (SI) is an innovative oral iron-containing carrier in which iron pyrophosphate is enclosed in a phospholipid matrix coated with sucrester, which protects sucrosomial iron from the effects of gastric juice, excluding contact with the mucous membrane of the gastrointestinal tract. Resistance to the action of gastric juice allows intact sucrosomes to reach the mucous membrane of the small intestine, where they are absorbed through special M cells, followed by the release of iron in liver cells. This allows prescribing SI to patients with iron deficiency and inflammatory bowel diseases, celiac disease, cancer and patients with obesity. Sucrosomial iron should be considered as an alternative treatment for iron deficiency in obese women. SI is innovative, allowing to bypass the “hepcidin barrier”, convenient for administration, effective for treatment, well tolerated than traditional oral iron salts.

Influence of TMPRSS6 genotype on iron status parameters in stable COPD patients

Background: The SNP rs855791 has been linked to increased hepcidin levels, variations in serum iron, transferrin saturation and red blood cell indices. Our goal was to determine the prevalence of this polymorphism among COPD patients and to assess its impact on iron status parameters including hepcidin in patients with stable COPD. Methods: We analysed iron status parameters and genetic data form 94 COPD patient: 29 patients with wild-type genotype (WT group) and 65 patients with either homozygous or heterozygous genotype (HH group). Additionally, the prevalence of SNP rs855791 was assessed in 192 volunteers. Results: The frequency distribution of SNP rs855791 was comparable between the COPD patients and control subjects (p=0.791). Iron status parameters were within their respective reference values and did not show neither statistically nor clinically significant difference between the WT and HH group of COPD patients. However, after excluding patients with (sub)clinical vitamin B12 deficiency and/or hypoxemia, WT group of patients exhibited significantly lower erythropoietin levels (p=0.015). The area under the curve for EPO was 0.688 (95% CI: 0.545-0.830, p=0.015), with an optimal cut-off of 9.74, sensitivity of 61.2% (95% CI: 58.1-64.3) and specificity of 65.0% (95% CI: 61.8-68.3). Conclusion: In patients with stable COPD, iron status parameters do not differ between WT and HH group of patients. After excluding those with (sub)clinical vitamin B12 deficiency and/or hypoxia, only statistical and not clinical difference in EPO levels was observed suggesting that EPO may regulate hepcidin levels and thus influence the development of iron deficiency and/or anaemia.

Expression of Concern.

The Editor in Chief and the Publisher are issuing an expression of concern to alert readers that the following article is under investigation due to a potential ethical breach regarding lack of transparency in the transplantation procedure as outlined in the article published by Rogers W et al (DOI: 10.1136/bmjopen-2018-024473): - Chen J, Zhong L. Clinical significance of serum hepcidin-25 levels in predicting invasive fungal disease in patients after transplantation. Eur Rev Med Pharmacol Sci 2013; 17 (13): 1769-1773-PMID: 23852902. Further updates will be provided once the investigation is completed. The authors have been notified about the ongoing investigation and the publication of this expression of concern.

Effect of dietary protein on serum hepcidin and iron in adults with obesity and insulin resistance: A randomized single blind clinical trial.

Background and AimsBoth obesity and iron deficiency are public health problems. The association between the two problems could be explained by chronic low-grade inflammation in obesity, which could stimulate hepcidin expression and modify iron concentration that the consumption of high-protein diets could prevent. Thus, this study aimed to compare the effects of high-protein diets with a predominance of animal or vegetable protein on serum hepcidin and iron concentrations in adults with obesity. Methods and ResultsThis randomized clinical trial involved adults with obesity and insulin resistance, who were assigned to either a high animal protein (AP) group or a high vegetable protein (VP) group for a one-month intervention. Both groups followed a calorie-restricted diet, reducing energy intake by 750 kcal/day. Baseline and final measurements included serum concentrations of hepcidin and iron, biochemical parameters, anthropometric data, and body composition. A total of 33 participants (63% female) were included in the study. Significant weight loss was observed in both groups after the intervention. Adjusted for weight loss percentage, the AP group showed a significant increase in hepcidin concentration (from 22.3 ± 14.7 to 27.5 ± 19.5 ng/mL) compared to the VP group (from 17.9 ± 15.1 to 17.2 ± 10.1 ng/mL) (p < 0.01), with no changes in serum iron concentration. Additionally, the VP diet significantly reduced serum adiponectin (p = 0.04) and C-reactive protein (p = 0.03) levels. ConclusionsIn adults with obesity following the AP diet for one month, hepcidin levels increased without affecting serum iron concentrations. Trial registrationNCT03627104

Inflammatory biomarkers and hepcidin levels in Iron deficiency anemia among women of reproductive age

Inflammatory biomarkers and hepcidin levels in Iron deficiency anemia among women of reproductive age

The Relationship Between Ghrelin and Iron Metabolism In Beta Thalassemia Major Patients

IntroductionStudies in beta thalassemia major (β-TM) patients have shown that the responses of HIF2α, hepcidin and ferroportin molecules to high iron levels are impaired. In recent years, studies conducted in patients with iron deficiency anemia have investigated the relationship between ghrelin hormone and iron metabolism. In this study, we aimed to contribute to the etiopathogenesis of this disease by examining the changes in ghrelin hormone levels in patients with β-TM.Material and methodsFifty-two β-TM and 23 controls were included in our study. Blood counts, routine biochemical parameters, HIF2α, hepcidin and ghrelin levels were studied in blood samples taken from the volunteers.ResultsErythrocyte indexes, serum bilirubin, iron, unsaturated iron binding capacity, total iron binding capacity and ferritin levels showed significant differences between two groups (p&lt;0.05) . There was no significant difference between two groups for serum HIF2α and hepcidin levels. When two groups were compared, ghrelin levels were found to be significantly higher in patients (p&lt;0.05). When the correlation between parameters was examined in all subjects, a weak positive correlation was found between ghrelin and HIF2α (r=0.263) (p&lt;0.05) and a significant positive correlation was found between ghrelin and ferritin (r=0.417) (p&lt;0.05).ConclusionsOur study showed that there is a positive correlation between ghrelin and ferritin levels. Elevated ghrelin levels in patients with β-TM may have an important role in regulating impaired iron metabolism. Molecular level studies are needed to determine synthesis pathways.

Hepcidin, GDF-15 and their Impact on Iron Metabolism in CKD

Background Anemia is an important complication in chronic kidney disease (CKD). We studied the diagnostic accuracy of hepcidin and growth differentiation factor-15 (GDF-15) as early markers of iron deficiency anemia (IDA) in non-dialysis (ND-CKD) patients. Materials and Methods This was a cross-sectional, case-control study comprising 100 cases of CKD (newly diagnosed and non-dialyzed) and 40 healthy controls. Serum levels of hepcidin and GDF-15 were estimated using ELISA-based assays. Receiver operator characteristics were used to evaluate the diagnostic validity of hepcidin and GDF-15 for absolute and functional iron deficiency anemia. Results About 33% of the cases were females with a mean age of 47.64 (± 13.68) years. The predictive value of hepcidin for diagnosing functional IDA in CKD was found to be 69.1% (95% CI: 52.5% to 82.7%), and that of GDF-15 was found to be 68.8% (95% CI: 52.6% to 82.1%). Hepcidin significantly correlated with hemoglobin (r = 0.278, p = 0.005) and serum iron (r = 0.222; p = 0.025). GDF-15 positively correlated with ferritin (r = 0.346, p &lt; 0.0001) and hsCRP (r = 0.223, p = 0.0088) and negatively correlated with eGFR (r = -0.462, p &lt; 000001), Hb (r = -0.481, p &lt; 0.00001) and TIBC (r = -0.353, p &lt; 0.0001). Conclusion Hepcidin and GDF-15 could predict functional IDA in our patients but not absolute IDA.

The hepcidin-ferroportin axis modulates liver endothelial cell BMP expression to influence iron homeostasis in mice

AbstractThe liver hormone hepcidin regulates systemic iron homeostasis to provide enough iron for vital processes while limiting toxicity. Hepcidin acts by degrading its receptor ferroportin (encoded by Slc40a1) to decrease iron export to plasma. Iron controls hepcidin production in part by inducing liver endothelial cells (LECs) to produce bone morphogenetic proteins (BMPs) that activate hepcidin transcription in hepatocytes. Here, we used in vitro and in vivo models to investigate whether ferroportin contributes to LEC intracellular iron content to modulate BMP expression and, thereby, hepcidin. Quantitative proteomics of LECs from mice fed different iron diets demonstrated an inverse relationship between dietary iron and endothelial ferroportin expression. Slc40a1 knockdown primary mouse LECs and endothelial Slc40a1 knockout mice exhibited increased LEC iron and BMP ligand expression. Endothelial Slc40a1 knockout mice also exhibited altered systemic iron homeostasis with decreased serum and total liver iron but preserved erythropoiesis. Although endothelial Slc40a1 knockout mice had similar hepcidin expression to control mice, hepcidin levels were inappropriately high relative to iron levels. Moreover, when iron levels were equalized with iron treatment, hepcidin levels were higher in endothelial Slc40a1 knockout mice than in controls. Finally, LEC ferroportin levels were inversely correlated with hepcidin levels in multiple mouse models, and treatment of hepcidin-deficient mice with mini-hepcidin decreased LEC ferroportin expression. Overall, these data show that LEC ferroportin modulates LEC iron and consequently BMP expression to influence hepcidin production. Furthermore, LEC ferroportin expression is regulated by hepcidin, demonstrating a bidirectional communication between LECs and hepatocytes to orchestrate systemic iron homeostasis.

Preterm Piglets Born by Cesarean Section as a Suitable Animal Model for the Study of Iron Metabolism in Premature Infants.

Preterm infants are most at risk of iron deficiency. However, our knowledge of the regulation of iron homeostasis in preterm infants is poor. The main goal of our research was to develop and validate an animal model of human prematurity to assess iron status in preterm infants. We performed a cesarean section on sows on the 109th day of pregnancy, which corresponds to the last trimester of human pregnancy. Preterm piglets showed decreased body weight, red blood cell indices, plasma iron level and transferrin saturation. Interestingly, higher hepatic and splenic non-heme iron content and plasma and hepatic ferritin levels were found in premature piglets compared with term ones. In addition, premature piglets showed higher mRNA levels of iron-regulatory hormone hepcidin in the liver than term animals, which have not been reflected in higher plasma hepcidin-25 levels. We also showed changes in hepcidin regulators, including hepatic bone morphogenetic protein 6, plasma erythroferrone and growth differentiation factor 15 in preterm piglets. Consequently, no difference was observed in iron-exporter ferroportin levels in the spleen and liver. Overall, it seems that premature piglets show a pattern of iron metabolism characteristic of functional iron deficiency and iron accumulation in the tissue.

A novel synthetic compound, deferiprone–resveratrol hybrid (DFP-RVT), promotes hepatoprotective effects and ameliorates iron-induced oxidative stress in iron-overloaded β-thalassemic mice

A high amount of iron in β-thalassemia patients can lead to oxidative stress and organ dysfunction, especially liver, the main iron accumulated organ. Iron catabolism causes the generation of reactive oxygen species (ROS), triggering liver inflammation, fibrosis, and cirrhosis. Deferiprone-resveratrol hybrid (DFP-RVT) is chemically synthesized by combining deferiprone (DFP) and resveratrol (RVT) which shows an iron-chelating property along with antioxidant activity. This study explored the hepatoprotective effect of DFP-RVT in iron overloaded β-knockout (BKO) thalassemic mice. The results revealed that DFP-RVT treatment improved liver function in iron-overloaded BKO mice by reducing liver enzymes and increasing hepcidin levels compared to iron overload control mice. Both DFP alone and DFP-RVT treatment groups demonstrated iron chelation effects by decreasing liver iron content (LIC), iron profiles, and iron deposition in the liver. Moreover, DFP-RVT powerfully showed antioxidant properties by decreasing liver and plasma thiobarbituric acid reactive substances (TBARs) and increasing reduced glutathione (GSH) and superoxide dismutase (SOD). Interestingly, transforming growth factor β1 (TGFβ1), which can contribute to chronic liver disease through liver injury, inflammation, fibrosis, and cirrhosis, is highly expressed in iron-overloaded mice. However, both DFP and DFP-RVT treatment significantly reduced TGFβ1 levels compared to the iron-overloaded group. Therefore, DFP-RVT could be a potent hepatoprotective compound through the mobilization of iron, reduction of ROS, improvement of liver enzymes, and alleviation of liver damage, potentially relieving liver dysfunction in iron-overloaded BKO mice.

Predictive Value of Serum Hepcidin Levels for the Risk of Incident End-Stage Kidney Disease in Patients with Chronic Kidney Disease: The KNOW-CKD

Introduction: Despite the pivotal role of hepcidin in the development of anemia among the patients with chronic kidney disease (CKD), the association between serum hepcidin levels and CKD progression has been never investigated. We here hypothesized that elevation in serum hepcidin levels might be associated with the risk of incident end-stage kidney disease (ESKD) among the patients with pre-dialysis CKD. Methods: A total of 2,109 patients with pre-dialysis CKD at stages 1 to pre-dialysis 5 were categorized into the quartiles by serum hepcidin levels. The study outcome was incident ESKD. The median duration of follow-up was 7.9 years. Results: The analysis of the baseline characteristics revealed that unfavorable clinical features were in general associated with higher serum hepcidin levels. The cumulative incidence of ESKD was significantly differed by serum hepcidin levels, with the highest incidence in the 4th quartile (p < 0.001, by log-rank test). Cox regression analysis demonstrated that, compared to the 1st quartile, the risk of incident ESKD is significantly increased in the 4th quartile (adjusted hazard ratio 1.372, 95% confidence interval 1.070–1.759). Penalized spline curve analysis illustrated a linear, positive correlation between serum hepcidin levels and the risk of incident ESKD. Subgroup analyses revealed that the association is significantly more prominent in the patients with advanced CKD (i.e., estimated glomerular filtration rate <45 mL/min/1.73 m2). Conclusion: Elevation in serum hepcidin levels is significantly associated with the risk of incident ESKD among the patients with pre-dialysis CKD.

Hepcidin levels, markers of iron overload, and liver damage in children with beta-thalassemia major

Background Thalassemia is a hemoglobin synthesis disorder that causes patients to need lifelong blood transfusions, leading to iron overload and alter organ function, including the liver. Hepcidin, produced by the liver, plays a role in iron homeostasis and should be increased in excess iron stores. However, the level decreases in thalassemia due to some factors, such as ineffective erythropoiesis and liver damage. Recent publications revealed that hepcidin could be associated with iron overload and also a marker of liver diseases. Objective To analyse the correlation between hepcidin level, markers of iron overload, and liver damage in beta-thalassemia major. Methods This cross-sectional study included all ?-thalassemia major age 2-18 years admitted to Dr. Mohammad Hoesin Hospital, Palembang, South Sumatera, who underwent blood transfusions from March to August 2022. We measured the level of iron overload markers, hepcidin, liver function test (LFT), and performed liver ultrasonography (USG). Results Of 97 subjects, median hepcidin level was 10.01 ng/mL and 68% of the subjects showed a decrease. The iron overload parameters were evaluated from serum iron levels (P=0.13), ferritin levels (P=0.90), and transferrin saturation (P=0.29) and 24.7% had abnormal liver USG findings. Spearman’s correlation revealed that only direct bilirubin (DB) (r=0.35; P=0.001) and liver USG (r=0.20; P=0.05) had positive correlations with decreased levels of hepcidin. Also, it had 91.7% sensitivity in predicting liver damage from ultrasound. Conclusion The hepcidin level was not significantly associated with iron overload markers.

Serum Levels of the C-terminal Fragment of Fibroblast Growth Factor 23 (C-FGF23) and Hepcidin in Patients with Hemodialysis Undergoing Treatment with a Proline Hydroxylase Domain (PHD) Inhibitor

Background: We previously reported, for the first time, serum levels of the C-terminal fragment of fibroblast growth factor 23 (C-FGF23) in patients undergoing hemodialysis (HD). Most HD patients have undergone treatment with either recombinant erythropoietin (r-EPO) or hypoxia-inducible factor (HIF) proline hydroxylase domain (PHD) inhibitor, both of which stimulate FGF23 production and cleavage. Methods: This cross-sectional observational study involved analyzing measuring FGF-related parameters and comparing results for subgroups of patients who received either r-EPO and or a PHD inhibitor. Results: No significant difference was observed for iron-related parameters or serum hepcidin levels in both subgroups of patients. Significant differences were found for certain FGF-23-related parameters. Conclusion: Both FGF23 production and cleavage were stimulated more in patients treated with the PHD inhibitor than in patients treated with r-EPO.