Hepcidin-25 in diabetic chronic kidney disease is predictive for mortality and progression to end stage renal disease

Background: Anemia is common and is associated with impaired clinical outcomes in diabetic chronic kidney disease (CKD). It may be explained by reduced erythropoietin (EPO) synthesis, but recent data suggest that EPO-resistance and diminished iron availability due to inflammation contribute significantly. In this cohort study, we evaluated the impact of hepcidin-25—the key hormone of iron-metabolism—on clinical outcomes in diabetic patients with CKD along with endogenous EPO levels. Methods: 249 diabetic patients with CKD of any stage, excluding end-stage renal disease (ESRD), were enrolled (2003–2005), if they were not on EPO-stimulating agent and iron therapy. Hepcidin-25 levels were measured by radioimmunoassay. The association of hepcidin-25 at baseline with clinical variables was investigated using linear regression models. All-cause mortality and a composite endpoint of CKD progression (ESRD or doubling of serum creatinine) were analyzed by Cox proportional hazards models. Results...背景：贫血在糖尿病慢性肾脏病（diabetic chronic kidney disease, CKD）患者中十分常见，且与不良临床结局相关。其发病机制既往认为与促红细胞生成素（erythropoietin, EPO）合成减少有关，但近期研究表明，促红细胞生成素抵抗以及炎症介导的铁利用不足同样发挥了重要作用。本队列研究旨在探讨铁调素-25（hepcidin-25）——铁代谢的关键激素——联合内源性促红细胞生成素水平，对糖尿病慢性肾脏病患者临床结局的影响。方法：本研究于2003—2005年间纳入249例各分期非终末期肾病（end-stage renal disease, ESRD）的糖尿病慢性肾脏病患者，纳入标准为未接受促红细胞生成素刺激剂与铁剂治疗。采用放射免疫法检测受试者血清铁调素-25水平。通过线性回归模型分析基线铁调素-25水平与临床变量的相关性。采用Cox比例风险模型分析全因死亡率以及慢性肾脏病进展复合终点（终末期肾病或血清肌酐翻倍）的发生风险。结果……