Serum hepcidin concentration in chronic haemodialysis patients: associations and effects of dialysis, iron and erythropoietin therapy

Background Hepcidin, a liver‐derived peptide induced by iron overload and inflammation, is a major regulator of iron homeostasis. As hepcidin decreases gastrointestinal iron absorption and recirculation from monocytes, over‐expression is associated with the development of anaemia. Methods We studied the associations between circulating hepcidin levels and various laboratory parameters related to anaemia and/or inflammation in 20 patients on chronic haemodialysis. Furthermore, we determined the impact of dialysis and iron and/or erythropoietin (rhEpo) supplementation therapy on hepcidin serum concentrations. The patients were withheld from iron and rhEpo for 2 weeks before study entry. Hepcidin was measured by liquid chromatography‐mass spectrometry (LC‐MS/MS); serum iron and haematological parameters, cytokines and pro‐hepcidin by commercially available enzyme‐linked immunosorbent assays (ELISA) or standard automated methods. Results While hepcidin levels at baseline were not correlated to pro‐hepcidin, interleukin‐6 or transforming growth factor‐beta concentrations, we found significant associations with reticulocyte count (r = ?0·55; P = 0·015), serum iron (r = 0·7; P = 0·004) and ferritin levels (r = 0·63; P = 0·004) and transferrin saturation (r = 0·69, P = 0·001). Dialysis using either a high or a low flux biocompatible dialyser resulted in a significant decrease of hepcidin concentrations, which returned to pre‐dialysis values before the next dialysis session. When studying the effects of anaemia treatment, we observed a significant reduction of hepcidin levels following administration of rhEpo but not iron. Conclusions Hepcidin levels in stable haemodialysis patients appear to reflect systemic iron load, but not inflammation. Due to the negative association between reticulocyte counts and hepcidin, the reduction of circulating hepcidin concentrations by dialysis and/or rhEpo treatment may positively affect erythropoiesis.     

Ferritin iron content in haemodialysis patients: comparison with septic and hemochromatosis patients

Objectives

Hemodialysis (HD) population commonly show high plasma ferritin levels with a poor diagnostic value. The objective of this study is to elucidate the meaning of HD hyperferritinemia through the analysis of its ferritin iron content (FIC).

Design and methods

FIC (iron atoms/ferritin molecule) was measured by atomic emission spectrometry. Ferritin and FIC values were correlated with iron storage and inflammation markers and the results of HD patients compared to those of septic and hemochromatosis patients.

Results

1) In the whole HD population, high ferritin levels were associated to low FIC values; 2) the correlation of ferritin with iron indices and inflammation markers in HD patients was intermediate in between that of septic and hemochromatosis patients; 3) the FIC level of HD patients was lower than that of the other two groups.

Conclusions

The high ferritin levels of HD patients are not synonymous with either inflammation or of high levels of iron storage. Their high levels and the low FIC values might be due to the presence inside the ferritin core of oligoelements other than iron.     

静脉补铁对维持性血液透析患者的贫血及微炎症状态的影响

目的：探讨静脉补铁对维持性血液透析患者的贫血及微炎症状态的影响。方法：选择血液透析患者90例，随机分为静脉组（30例）、口服组（30例）和未补铁组（30例）。观察用药前后血红蛋白浓度、红细胞压积、血清铁、血清铁蛋白、转铁蛋白饱和度等疗效指标以及血清C反应蛋白、白介素-6、白介素-10、肿瘤坏死因子-α等炎症指标并监测不良反应。结果：8周后，静脉组血红蛋白水平及血清铁蛋白较治疗前明显改善（P〈0．01）；血浆及血清C反应蛋白，白介素-6，肿瘤坏死因子-α均较治疗前显著升高（P〈0．01或P〈0．05）。结论：静脉补铁有效改善患者的贫血及缺铁，也加剧了其炎症状态．     

Serum erythropoietin concentrations and iron status in patients on chronic hemodialysis.

We studied the relationship between serum erythropoietin (EPO) concentration and iron status in 67 patients undergoing chronic hemodialysis. Serum concentrations of EPO were measured by RIA with recombinant human EPO. The geometric mean of the serum EPO concentration was 10.9 int. units/L (mean +/- SD range = 7.8 - 15.3 int. units/L) in hemodialysis patients, considerably lower than that in normal subjects (12.9 int. units/L). We found no significant correlation between concentrations of serum EPO and hemoglobin in hemodialysis patients, but found a significant negative correlation between serum concentrations of EPO and iron in hemodialysis patients. Moreover, we also found a significant positive correlation between the EPO concentration and the unsaturated iron-binding capacity (UIBC) in serum, and a significant negative correlation between the serum concentrations of EPO and ferritin in hemodialysis patients. Several patients who had relatively high EPO concentrations for hemodialysis patients also had low iron concentrations, high UIBC values, and low ferritin concentrations. These findings suggest that iron was utilized even at these EPO concentrations, which were very low for the degree of anemia observed in the hemodialysis patients.     

Serum aluminum level correlates with arterial stiffness in haemodialysis patients

Background: In addition to pulse wave velocity (PWV), serum aluminum level is predictive of mortality in haemodialysis (HD) patients. This cross‐sectional study evaluated the correlations between serum aluminum and brachial‐ankle PWV (baPWV). Methods: One hundred twenty‐seven HD patients (average age 58.46 ± 9.95 years) were enrolled. Medical data were obtained via chart reviews and hospital database. Associations between biomarker levels and baPWV were analysed by multiple linear regression. Results: Serum aluminum, high sensitivity C‐reactive protein (hsCRP), age, pulse pressure (PP), mean arterial pressure (MAP) and diabetes mellitus (DM) are important correlates of baPWV. Conclusion: Further, hsCRP, PP, age and DM are positively related to arterial stiffness in HD patients.     

终末期肾脏病患者血清中铁调素的水平变化及其与铁代谢的关系

目的研究维持性血液透析(maintenance hemodialysis,MHD)患者、非透析终末期肾脏病(end-stage renal disease,ESRD)患者血清中铁调素的水平及与其铁代谢的关系。方法选择MHD患者30例、非透析ESRD患者30例及健康体检者30例。酶联免疫吸附法检测血清铁调素、总铁结合力(total iron binding capacity,TIBC),同时测定血清铁、铁蛋白(ferritin,Fer)、血清转铁蛋白(transferrin,TRF),比较组间差异。结果 MHD患者和非透析ESRD患者血清铁调素水平显著高于正常人群,差异有统计学意义(P<0.01);MHD患者血清铁调素水平高于非透析ESRD患者,差异有统计学意义(P<0.05)。相关分析显示,血清铁调素与血清肌酐、高敏C反应蛋白(high sensitivity C-reactiveprotein,hs-CRP)、全段甲状旁腺激素、Fer呈正相关(r分别为0.969、0.515、0.290、0.286,均P<0.01);与血红蛋白(hemoglobin,Hb)、红细胞计数(red blood cell,RBC)、估算肾小球滤过率(estimated glomerular filtration rate,eGFR)、血细胞比容、TRF、Fe、TIBC、白蛋白、总蛋白呈负相关(r分别为-0.543、-0.540、-0.534、-0.466、-0.362、0.360、-0.285、-0.248、-0.224,P<0.05)。多元逐步回归分析显示,非透析ESRD患者中RBC、Hb、hs-CRP、Fer、TRF、TIBC与铁调素水平密切相关;MHD患者中RBC、Hb、eGFR、Fer、TIBC与铁调素水平密切相关。在非透析ESRD患者中,血清铁调素的受试者工作特征曲线(receiver operating characteristic curve,ROC)曲线下面积为86.3%,其敏感性和特异性分别为76.7%和99.1%;在MHD患者中,血清铁调素的ROC曲线下面积为84.6%,其敏感性和特异性分别为73.0%和99.8%。结论 ESRD患者血清铁调素水平明显增加,铁调素参与铁代谢、红细胞生成的调控,可能为反映铁储备状态的一种新型血清标志物。     

Hepatic computed tomography for monitoring the iron status of haemodialysis patients with haemosiderosis treated with recombinant human erythropoietin.

1. A randomized, partial-crossover study was conducted in uraemic patients with dialysis-associated anaemia and transfusional iron overload to evaluate the effects of desferrioxamine chelation therapy and of recombinant human erythropoietin treatment on hepatic iron storage determined by computed tomography, as well as by serum ferritin concentration and transferrin saturation. 2. Twenty-one haemodialysis patients with moderate iron overload, confirmed by values of serum ferritin concentration, transferrin saturation and hepatic computed tomography density exceeding 1000 micrograms/l, 45% and 68 Hounsfield units respectively, were randomly allocated to three groups and were followed for 12 months. 3. During the first 6 months group 1 (n = 7) received desferrioxamine chelation therapy (30 mg/kg intravenously three times a week) and group 2 (n = 7) underwent recombinant human erythropoietin treatment (36 units/kg intravenously three times a week). Thereafter, in the second 6 months of observation patients in group 1 were switched to receive recombinant human erythropoietin. Because of a poor response in the desferrioxamine-treated group in the initial 6 months, patients in group 2 continued on the maintenance dose of recombinant human erythropoietin (18 units/kg three times a week) until the end of the trial. Patients in group 3 (n = 7) were maintained on placebo throughout the study. 4. In comparison with placebo, recombinant human erythropoietin treatment, but not desferrioxamine chelation therapy, reduced serum ferritin concentration, transferrin saturation and hepatic computed tomography density, and was associated with a rise in haemoglobin and packed cell volume. Hepatic computed tomography density, serum ferritin concentration and transferrin saturation decreased in 13 out of 14 patients (93%) during treatment with recombinant human erythropoietin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effectiveness of oral and intravenous iron therapy in haemodialysis patients

Anaemia is a common and serious complication in patients with end-stage renal disease. Iron therapy is crucial in managing anaemia and maintenance of haemodialysis (HD) patients. This study investigated the efficacy of both oral and intravenous (i.v.) therapies, and the possible factors deleteriously affecting patient response to iron therapy. Forty patients on maintenance HD from a single institution were enrolled in this 6-month retrospective study. Group I (n = 20) received i.v. two ampoules of atofen (ferric chloride hexahydrate 193.6 mg) per week for a total of 6 weeks (total dosage, 960 mg). Group II (n = 20) received oral ferrous sulphate S.C. Tab (ferrous sulphate 324 mg) one pill three times daily (total dosage, 63,000 mg). Patients whose haematocrit (Hct) level increased at minimum 3% within the period were classified as responders. Iron i.v. ferric chloride (960 mg) was more effective than oral ferrous sulphate (63,000 mg) in correcting anaemia in HD patients with iron deficiency. In group I, serum triglyceride (TG) levels were significantly lower in patients responding to i.v. iron therapy than in patients with no response. In group II, serum high-sensitive C-reactive protein (hs-CRP) level was significantly lower in patients responding to oral iron therapy than patients with no response. The i.v. ferric chloride is more effective than oral ferrous sulphate in treating anaemia in HD patients with iron deficiency. Serum hs-CRP and TG levels may be parameters for predicting hyporesponsiveness to oral and i.v. iron therapies, respectively.     

Serum ferritin and iron status in 'healthy' elderly individuals

Iron status, including S-ferritin, S-iron, S-transferrin, transferrin saturation and haemoglobin, was assessed in 267 selected elderly subjects (128 male, 139 female) with a median age of 79 years (range 60-93 years) not suffering from diseases connected with inappropriately high S-ferritin. In both sexes, S-ferritin levels were practically constant over the examined age range. Males had a geometric mean ferritin of 75 micrograms/l and females a value of 60 micrograms/l (p less than 0.001). Levels of S-ferritin less than 15 micrograms/l (i.e. depleted iron stores) were found in 7.8% of males and in 10.1% of females. An S-ferritin level less than 15 micrograms/l and transferrin saturation less than 15% (i.e. latent iron deficiency) was observed in 2.3% of males and in 2.2% of females. None had iron deficiency anaemia. In subjects (n = 232) without iron deficiency [i.e. S-ferritin greater than or equal to 15 micrograms/l, mean red cell volume greater than or equal to 79 fl and haemoglobin greater than or equal to 121 g/l (7.5 mmol/l)], the arithmetic mean of S-iron was 18 mumol/l. S-transferrin 28 mumol/l and transferrin saturation 33%. The levels of S-iron, S-transferrin and transferrin saturation were not significantly different in males and females.     

Diagnostic accuracy of serum hepcidin for iron deficiency in critically ill patients with anemia

Purpose  

Inflammation-induced anemia is frequent among critically ill patients and can be aggravated by true iron deficiency (ID) resulting from blood losses. The serum hepcidin level controls the availability of iron for erythropoiesis, and its determination offers new perspectives for the diagnosis of ID in the presence of inflammation. We conducted a prospective observational study to determine the cutoff value and diagnostic accuracy of hepcidin levels for detecting ID in critically ill anemic patients.     

Serum butyrylcholinesterase activity and phenotype associations with lipid profile in stroke patients

Background

Butyrylcholinesterase (BuChE) catalyzes the hydrolysis of acetylcholine and other choline esters and is also involved in lipid metabolism. The purpose of this study was to investigate any association between BuChE serum phenotype and activity and lipid profile of ischemic stroke patients.

Methods

We determined serum BuChE activities and phenotypes, and levels of total cholesterol (TC), LDL-C, HDL-C and triacylglyerol (TG) in 33 patients with acute ischemic stroke within 12 h of the onset of the attack and 29 controls.

Results

The mean (± SD) serum BuChE activity and the BuChE of U/A phenotype in the stroke individuals were significantly lower and higher than that of the control (315 (± 124) IU/L. vs. 384 (± 99) IU/L, p = 0.02, t = − 2.4 and 21.2% vs.3.4%, p = 0.026 respectively).

Conclusions

Our results showed that a negative correlation between BuChE activity with TC level, in addition the frequency of BuChE phenotypes with low activity is high in stroke patients, who have high levels of cholesterol, may have increased susceptibility to stroke.     

羟苯磺酸钙治疗维持性血液透析患者微炎症及氧化应激状态的临床观察

目的 观察口服羟苯磺酸钙对维持性血液透析(maintenance hemodialysis,MHD)患者相关营养、微炎症及氧化应激状态的影响.方法 选择我院血液净化中心透析龄超过6个月的MHD患者62例,排除急性感染及其他活动性疾病,口服羟苯磺酸钙(2片,每日3次)治疗,进行为期6个月随访,分别检测治疗前、治疗1个月后、治疗6个月后患者的主要人体学指标、改良主观总体评价(SGA)评分、血生化指标、C反应蛋白(CRP)、白细胞介素6(IL-6)、白细胞介素1(IL-1)、肿瘤坏死因子α(TNF-α)、血浆丙二醛(MDA)、血浆谷胱甘肽过氧化物酶(GSHPx)、血浆总半胱氨酸(tHcy)、白蛋白(Alb)、前白蛋白(PA)、透析充分性(Kt/V>和蛋白分解代谢率(PCR).结果 ①治疗1个月后,MHD患者的干体质量、上臂肌围(MAMC)即有上升;治疗6个月后,患者平均干体质量、MAMC平均值较治疗前显著升高(P＜0.05).改良SGA评分较治疗前明显下降(P＜0.01).②治疗6个月后,MHD患者的血Alb治疗后(40±5)g/L较治疗前(37±5)g/L升高(P＜0.05),PA(292±33)mg/L和血红蛋白(Hb)(95±14)g/L治疗后较治疗前(247±23)mg/L和(88±12)g/L明显升高(P＜0.01).③CRP、IL-6、TNF-a、MDA、tHcy较治疗前明显下降(P＜0.01).④血总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)和脂蛋白(a)[Lp(a)]水平治疗前后差异无统计学意义(P＞0.05).⑤PCR值较治疗前明显上升(P＜0.01);两组Kt/V治疗前后无明显变化(P＞0.05).结论 羟苯磺酸钙可明显改善患者的营养状态,同时微炎症状态及氧化应激状态明显好转.     

腹膜透析患者幽门螺杆菌感染及其对微炎症、营养状态的影响

目的:调查腹膜透析(peritoneal dialysis,PD)患者幽门螺杆菌(Helicobacter pylori,Hp)感染情况,以及Hp感染对患者微炎症状态和营养状态的影响。方法:选择万宁市人民医院肾内科于2016年1月至2020年1月期间收治的178例持续性非卧床PD患者为研究对象。行14C尿素呼气试验(14C-urea breath test,14C-UBT)检查以确定是否存在Hp感染,测定血清C反应蛋白(C-reactive protein,CRP)以及白蛋白(albumin,ALB),前白蛋白(prealbumin,PAB)浓度。比较Hp阳性及阴性者上述指标的差异,以及Hp阳性者抗Hp治疗前后上述指标的变化。结果:PD患者Hp感染发生率为41.57%;Hp阳性组患者的血清CRP水平明显高于Hp阴性组,而血清Alb,PAB水平明显低于Hp阴性组,差异均有统计学意义(均P<0.05);Hp阳性患者抗Hp治疗后,患者的血清CRP水平较治疗前明显降低,血清Alb、PAB水平明显升高,差异均有统计学意义(均P<0.05)。结论:PD患者Hp感染会加重患者的微炎症状态和营养不良,抗Hp治疗对改善微炎症状态和营养不良有利。     

Serum iron determination in patients receiving therapy with iron dextran ("Imferon").

Imferon (Lakeside Labs., Inc.), an iron dextran complex, is widely used for parenteral therapy with iron. Colorimetry and atomic absorption spectroscopy give different values for serum iron concentration in patients receiving such therapy. Values determined by atomic absorption spectroscopy were usually much higher than those obtained by either a manual or an automated colorimetric procedure, and also were higher than the total serum iron-binding capacity of the same sera. This difference is attributed to circulating iron being present both as iron dextran as as transferrin-bound iron. We conclude that atomic absorption spectroscopy should be used to determine serum iron in patients receiving Imferon.     

The aminothiol redox status in haemodialysis patients does not improve with folate therapy

Background. Patients on haemodialysis suffer from high cardiovascular morbidity and mortality, and oxidative stress may play a role in the pathophysiology of cardiovascular disease in these patients. Hyperhomocysteinemia is common in dialysis patients and may have pro‐oxidant effects. Moreover, the redox status of the major plasma aminothiols (homocysteine [Hcy], cysteine and cysteinylglycine) may be regarded as a biomarker of oxidative stress. In the present study, we investigated the aminothiol redox status during a period of homocysteine‐lowering therapy with folinic acid. Material and methods. In the first part of the study, 32 stable patients receiving maintenance haemodialysis were compared with 32 reference subjects. In the second part, the patients were given folinic acid intravenously for 3 months. Results. Before intervention with folinic acid, the patients had elevated concentrations of all redox species of Hcy. The aminothiol redox ratios were low. Folinic acid therapy lowered the concentrations of all Hcy redox species; however, the redox ratios did not improve. Conclusions. The low aminothiol redox ratios indicate the presence of oxidative stress in haemodialysis patients. Therapy with folinic acid lowered total Hcy concentrations, but did not improve the redox status. Thus, hyperhomocysteinemia appears to be of little importance in regard to the total level of oxidative stress in uraemia.     

2型糖尿病肾病血液透析患者心理状况探讨

目的 探讨2型糖尿病肾病血液透析患者的心理状况及相关因素,为患者心理康复提供依据。方法 糖尿病肾病患者30例,以及随机选取非糖尿病肾病患者30例。使用焦虑自评量表和抑郁自评表分别评估患者的情绪状况,并测定患者的营养状况、残余肾功能和透析的充分性等指标。结果 糖尿病肾病血透组患者焦虑和抑郁检出率均高于非糖尿病肾病组（P〈0．05）;糖尿病肾病营养不良患者焦虑和抑郁评分均高于营养良好者（P〈0．01）。血清白蛋白、标准化氮出现率相当蛋白、平均每日每公斤体质量的蛋白质摄入量、尿素清除指数和肌酐清除率等指标与糖尿病肾病血透组患者焦虑评分（P〈0．05）及抑郁评分（P〈0．05）呈明显负相关。而平均每日每公斤体质量的热量与焦虑评分、抑郁评分无明显相关性（P〉0．05）。结论 糖尿病肾病血透患者焦虑和抑郁症状的检出率较高,可能与营养不良有一定的关系,焦虑、抑郁的发生与性别、应激因素及病程有关。     

重组促红细胞生成素对血液透析患者铁代谢的影响

目的测定维持性血液透析患者血清促红细胞生成素（erythropoietin，EPO）及铁参数，探讨血液透析患者的铁代谢状况及重组EPO（recombinant human erythropoietin，rh-EPO）治疗对铁代谢的影响。方法选择单纯血液透析和接受rh-EPO治疗的血液透析患者31例，分别测定血常规及血清EPO、铁参数，并与健康对照组进行比较。结果血液透析患者和rh-EPO治疗的血液透析患者BBC、Hb、Hct、SI、TS显著低于健康对照组（P〈0．05，P〈0．01），SF、sTrFR和TIBC高于健康对照组，尤其是sTrFR和血液透析组的SF显著升高（P〈0．05）。血清EPO的检测3组间无明显差异。结论血液透析患者存在贫血伴缺铁及铁代谢紊乱。给予rh-EPO治疗可改善肾性贫血，同时改善铁代谢紊乱。rh-EPO的应用对血液透析患者体内EPO水平影响不大。