腹膜透析患者血清hepcidin水平及其与贫血和铁代谢指标的关系研究
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摘要
目的:Hepcidin是调节机体铁稳态的一种抗菌肽。本文探讨腹膜透析对血清hepcidin水平的影响,以及血清hepcidin水平与ESRD腹膜透析患者贫血和铁代谢等相关指标的关系。
     方法:收集苏州大学附属第二医院肾内科2010年6月至2010年12月住院的尿毒症行维持性透析治疗患者62例,其中腹膜透析治疗患者(PD组)40例,维持性血液透析患者(MHD组)22例,我院体检中心健康对照组15例。三组间年龄、性别相匹配。抽取空腹静脉血检测血常规、血生化、电解质、贫血检测等相关指标。用酶联免疫吸附试验(ELISA法)检测血清hepcidin、血清IL-6水平。计算PD组每周尿素清除率(Kt/V),促红细胞生成素抵抗指数(erythropoietin resistance index ,ERI)。统计学处理采用SPSS 13.0统计软件包,以P <0.05认为差异具有统计学意义。
     结果:
     1.与健康对照组比较,PD组和MHD组血清hepcidin、IL-6水平均明显升高(P <0.05);实验组中,PD组和MHD组血清hepcidin、IL-6水平无明显差异性(P >0.05)。
     2. PD组hepcidin水平与贫血和铁代谢指标的pearson相关性分析显示:hepcidin与铁蛋白(r=0.422,P =0.007)、血清铁(r=0.403,P=0.010)、IL-6(r=0.319,P=0.045)呈正相关,与可溶性转铁蛋白受体(r=-0.343,P=0.030)呈负相关。多元逐步回归分析表明,血清铁蛋白(β=0.331,P=0.031)、血清铁(β=0.303,P=0.048)是血清hepcidin的显著相关因素。
     3. PD组依据Kt/V值,将患者分为透析充分组和透析非充分性组,透析充分组患者铁蛋白水平明显升高(P<0.05),两组患者Hb、hepcidin、IL-6、其他铁代谢指标无明显差异性(P >0.05)。
     4. PD组依据入院前一月EPO、铁剂使用情况,分为EPO联合铁剂组、EPO组、铁剂组,发现单用EPO组Hb、血清hepcidin水平明显低于EPO联合铁剂组,差别具有统计学意义(P<0.05)。
     5. PD组使用EPO治疗的患者促红细胞生成素抵抗指数(ERI)与铁代谢、炎症指标的pearson相关性分析显示:ERI值与血清hepcidin(r=0.410,P =0.014)、IL-6(r=0.400,P =0.017)正相关。多元逐步回归分析表明,血清hepcidin(β=0.410,P=0.014)是ERI的显著相关因素。
     结论:
     1. ESRD患者普遍存在高hepcidin血症,透析方式对血清hepcidin水平无明显影响。
     2. Hepcidin能反映机体铁代谢状态,可能参与腹透患者功能性铁缺乏、EPO抵抗的发生和发展。
     3. Hepcidin可作为腹透患者贫血检测的一项新指标,为透析患者贫血治疗提供新的思路和方法。
Objective: Hepcidin is an anti-bacterial peptide which plays an important role in regulating iron homeostasis in human body. This research is expected to investigate the level of serum hepcidin and its relationship with the related index of anemia and iron metabolism in PD patients.
     Methods: From June to December 2010, 62 cases of patients treated with maintenance dialysis therapy were enrolled in this study, who were hospitalized in the nephrology department of the Second Affiliated Hospital of Soochow University. The PD treatment group (PD group) was 40 cases, Maintenance hemodialysis treatment group (MHD group) was 22 cases, 15 cases of healthy controls were also enrolled. The age and gender among the three groups were matched. Serum hepcidin and interleukin-6 levels were tested by enzyme-linked immunosorbent assay (ELISA). Fasting venous blood samples were extracted to detect the related index of routine blood test, blood biochemistry, electrolyte, anemia and et al. The Kt/V per week was calculated in the PD treatment group. The erythropoietin resistance index was calculated. All statistical analysis were performed with SPSS13. 0. P<0.05 was considered statistically significant.
     Results: 1. Compared with normal controls, PD group and MHD group had higher serum hepcidin and IL-6 (P<0.05). The levels of serum hepcidin and IL-6 had no significant difference (P >0.05).
     2. In PD group, serum hepcidin levels were positively correlated with serum ferritin (r=0.422,P=0.007)、serum iron (r=0.403,P=0.010)、interleukin-6 (r=0.319,P=0.045), but negatively correlated with serum transferrin receptor (r=-0.343,P=0.030). Multiple linear stepwise regression analysis showed that Fer (β=0.331, P=0.031) and Fe (β=0.303, P=0.048) were obvious correlating factors to hepcidin.
     3. According to the value of Kt/V, we divided patients into two groups, there are patients with and without adequacy dialysis. The patients with adequancy dialysis had higher ferritin(P<0.05). The levels of hemoglobin, serum hepcidin , IL-6 and other related index of iron metabolism had no significant difference in the two groups (P>0.05).
     4. According to the therapy of EPO and iron in the last month before hospitalization, we divided patients into three groups treated with EPO alone, iron alone and the combination of them. We found that the levels of hemoglobin and serum hepcidin was lower in the group treated EPO only compared to the group treated with EPO and iron. The difference had significant (P <0.05).
     5. In the patients treated with EPO,the erythropoietin resistance index was positively correlated with serum hepcidin (r=0.410,P=0.014) and IL-6(r=0.400,P=0.017). Multiple linear stepwise regression analysis showed that hepcidin (β=0.410, P=0.014) was obvious correlating factor to ERI.
     Conclusion: 1. ESRD patients generally have higher serum hepcidin level. The effects of different patterns of dialysis on serum hepcidin level had no significant.
     2. Hepcidin can reflect the iron status in human body. It may attend the development of functional iron deficiency and EPO resistance in peritoneal patients.
     3. As a new marker, hepcidin can be used as a reflection of anemia in peritoneal patients, it can be helpful to give a new way to treat renal anemia.
引文
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