Data from: 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: Patients (age 67 yrs, 53% male, GFR 51 ml/min, hemoglobin 131 g/L, EPO 13.5 U/L, hepcidin-25 62.0 ng/ml) were followed for a median time of 4.2 yrs. Forty-nine patients died (19.7%) and forty (16.1%) patients reached the composite endpoint. Elevated hepcidin levels were independently associated with higher ferritin-levels, lower EPO-levels and impaired kidney function (all p<0.05). Hepcidin was related to mortality, along with its interaction with EPO, older age, greater proteinuria and elevated CRP (all p<0.05). Hepcidin was also predictive for progression of CKD, aside from baseline GFR, proteinuria, low albumin- and hemoglobin-levels and a history of CVD (all p<0.05). Conclusions: We found hepcidin-25 to be associated with EPO and impaired kidney function in diabetic CKD. Elevated hepcidin-25 and EPO-levels were independent predictors of mortality, while hepcidin-25 was also predictive for progression of CKD. Both hepcidin-25 and EPO may represent important prognostic factors of clinical outcome and have the potential to further define “high risk” populations in CKD.背景：贫血在糖尿病慢性肾脏病（CKD）患者中十分常见，且与不良临床结局相关。其发病机制可能与促红细胞生成素（EPO）合成减少有关，但近期研究表明，EPO抵抗及炎症介导的铁利用降低在其中发挥了重要作用。本队列研究旨在评估铁代谢关键激素——铁调素-25，对糖尿病CKD患者临床结局的影响，并同时分析内源性EPO水平的关联。 方法：本研究于2003-2005年间纳入249例各分期糖尿病CKD患者（排除终末期肾病（ESRD）），纳入标准为未接受促红细胞生成素刺激剂及铁治疗。采用放射免疫分析法检测血清铁调素-25水平。通过线性回归模型分析基线铁调素-25与临床变量的关联。采用Cox比例风险模型分析全因死亡率及CKD进展复合终点（ESRD或血清肌酐翻倍）的发生风险。 结果：本研究纳入患者的基线特征为：年龄67岁，男性占53%，肾小球滤过率（GFR）51 ml/min，血红蛋白131 g/L，EPO 13.5 U/L，铁调素-25 62.0 ng/ml；中位随访时间为4.2年。共有49例患者死亡（占比19.7%），40例患者达到CKD进展复合终点（占比16.1%）。升高的铁调素水平与铁蛋白水平升高、EPO水平降低及肾功能损害独立相关（均P<0.05）。铁调素与死亡率相关，其与EPO的交互作用、年龄增加、蛋白尿加重及C反应蛋白（CRP）升高均与死亡率显著相关（均P<0.05）。除基线GFR、蛋白尿、低白蛋白及血红蛋白水平、心血管疾病（CVD）病史外，铁调素对CKD进展亦具有预测价值（均P<0.05）。 结论：本研究发现，在糖尿病CKD患者中，铁调素-25与EPO及肾功能损害相关。升高的铁调素-25及EPO水平是全因死亡率的独立预测因子，而铁调素-25同时可预测CKD进展。铁调素-25与EPO均可作为临床结局的重要预后因素，有望进一步明确CKD患者中的“高危”人群。