维持性血液透析患者血浆铁调素水平及其影响因素分析

Plasma hepcidin level and its related factors in maintenance hemodialysis patients

目的检测维持性血液透析(maintenance hemodialysis,MHD)患者血浆铁调素(hepcidin)水平,分析其与贫血相关指标和血管钙化的相关性,探讨其在MHD患者中的应用价值。方法纳入2011年1月至2011年12月期间于上海交通大学医学院附属瑞金医院血液透析中心长期MHD患者,记录患者入组时一般资料及生化指标。收集患者透析前血浆标本,应用酶联免疫吸附法测定血浆hepcidin水平,分析hepcidin与贫血相关指标、红细胞生成刺激剂(erythropoiesis stimulating agent,ESA)、铁代谢指标、C反应蛋白(C-reactive protein,CRP)之间的相关性,探讨hepcidin的危险因素及其与血管钙化之间的关系。结果 216例MHD患者中位hepcidin水平2952.66(1131.38,6076.72)pg/ml。Hepcidin水平与红细胞计数(r=-0.203,P=0.003)、血红蛋白(r=-0.165,P=0.015)、红细胞比容(r=-0.182,P=0.007)、总铁结合力(r=-0.467,P<0.001)、转铁蛋白(r=-0.362,P<0.001)呈显著负相关,与平均血红蛋白量(r=0.163,P=0.017)、平均血红蛋白浓度(r=0.156,P=0.022)、转铁蛋白饱和度(r=0.193,P=0.004)、铁蛋白(r=0.681,P<0.001)、CRP(r=0.301,P<0.001)、每周ESA剂量(r=0.146,P=0.032)呈显著正相关;逐步多元线性回归显示体质量指数(body mass index,BMI)(β=1.360,95%CI 0.437~2.283,P=0.004)、铁蛋白(β=0.061,95%CI 0.046~0.077,P<0.001)、CRP(β=3.532,95%CI 0.887~6.177,P=0.009)是影响hepcidin水平的独立危险因素,总铁结合力(β=-0.729,95%CI-1.170^-0.288,P=0.001)是保护因素。Hepcidin水平与腹主动脉钙化(aorta abdominalis calcification,AAC)受累节段(r=0.189,P=0.028)、腹主动脉钙评分(r=0.178,P=0.039)显著正相关。结论 MHD患者hepcidin水平与贫血、铁代谢指标显著相关,且与炎症指标、AAC也显著相关,提示hepcidin可能参与了MHD患者微炎症状态和血管钙化的病理学机制。

Objective To investigate plasma hepcidin level, the potential factors relating to hepcidin level, and its association with anemia and vascular calcification in maintenance hemodialysis（MHD） patients.Methods The MHD patients treated in Shanghai Ruijin Hospital from Jan. 1st, 2011 to Dec. 31 st, 2011 were enrolled in this study. Clinical characteristics and biochemical indices at baseline were collected. Blood samples at baseline were collected to determine plasma hepcidin level using ELISA method. The relationship between hepcidin level and anemia parameters and abdominal aortic calcification（AAC） was analyzed. Results A total of 216 MHD patients were enrolled in this study. The median plasma hepcidin level was 2,952.66（1,131.38~6,076.72） pg/ml. Spearman analysis showed that significant negative correlations were observed between hepcidin level and red blood cell（r=-0.203, P=0.003）, hemoglobin（r=-0.165, P=0.015）, hematocrit（r=- 0.182, P=0.007）, total iron binding capacity（r=- 0.467, P〈0.001） and transferrin（r=- 0.362, P〈0.001）;significant positive correlations were found between hepcidin level and mean corpuscular hemoglobin（r=0.163, P=0.017）, mean corpuscular hemoglobin concentration（r=0.156, P=0.022）, transferrin saturation（rr=0.193, P=0.004）, ferritin（r=0.681, P 0.001）, C- reactive protein（CRP）（r=0.301, P〈0.001）, and weekly ESA dose（r=0.146, P=0.032）. Stepwise multivariate regression analysis showed that BMI（β=1.360, 95% CI0.437~2.283, P=0.004）, ferritin（β =0.061, 95% CI 0.046~0.077, P〈0.001）, and CRP（β =3.532, 95% CI0.887~6.177, P=0.009） were the independent risk factors for the increase of hepcidin level, and total ironbinding capacity（β=-0.729, 95% CI-1.170^-0.288, P=0.001） was the independent inhibition factor for the increase of hepcidin level. Hepcidin level was positively correlated with AAC. Conclusion Plasma hepcidin level was related to anemia and iron metabolism parameters, inflammation factors and AAC, implying that hepcidin may participate in the pathogenesis of micro-inflammation state and vascular calcification.