Hepcidin and diabetes are independently related with soluble transferrin receptor levels in chronic dialysis patients

<b>Background:</b> Soluble transferrin receptor (sTfR) is a biomarker of erythropoiesis, which is often impaired in dialysis patients. The aim of our study was to evaluate sTfR levels in chronically dialyzed patients and assess potential determinants of its levels. <b>Methods:</b> We performed a cross-sectional study by evaluating 246 end-stage renal disease patients undergoing dialysis and 32 healthy controls. Circulating levels of interleukin (IL)-6, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, hepcidin, sTfR, growth differentiation factor 15 (GDF15), and traditional iron metabolism markers were measured, as well as hemogram parameters. Clinical data was obtained from all patients. <b>Results:</b> Compared to controls, patients presented similar values of sTfR, reticulocytes and reticulocyte production index (RPI), and significantly higher levels of IL-6, CRP, ferritin, hepcidin, TNF-α, and GDF15. Iron, transferrin, hemoglobin levels, erythrocyte count, mean cell hemoglobin (MCH), and mean cell hemoglobin concentration (MCHC) values were significantly lower in dialysis group. Within patients, sTfR values were higher in diabetic patients and were positively and significantly correlated with reticulocytes and erythrocytes, RPI, and therapeutic doses of erythropoiesis stimulating agents (ESA) and intravenous iron; and inversely and significantly correlated with circulating iron, ferritin, transferrin saturation, hepcidin, MCH, and MCHC. In multiple linear regression analysis, ESA dose, RPI, serum iron, diabetes, and hepcidin levels were independently associated with sTfR levels in dialysis patients and, thus, with erythropoiesis. <b>Conclusion:</b> Our data suggest that, besides RPI and ESA dose, diabetes and hepcidin are closely related to erythropoiesis in dialysis patients. The influence of diabetes on sTfR levels deserves further investigation.

<b>背景:</b> 可溶性转铁蛋白受体（soluble transferrin receptor, sTfR）是红细胞生成的生物标志物，而透析患者常存在红细胞生成受损的情况。本研究旨在评估慢性透析患者体内的sTfR水平，并分析其水平的潜在影响因素。
<b>方法:</b> 本研究为横断面研究，共纳入246例接受透析治疗的终末期肾病（end-stage renal disease, ESRD）患者以及32名健康对照者。检测了受试者外周血中白细胞介素（interleukin, IL）-6、C反应蛋白（C-reactive protein, CRP）、肿瘤坏死因子（tumor necrosis factor, TNF）-α、铁调素、sTfR、生长分化因子15（growth differentiation factor 15, GDF15）以及传统铁代谢标志物的水平，同时检测了血常规参数。此外，收集了所有患者的临床资料。
<b>结果:</b> 与健康对照者相比，透析患者的sTfR、网织红细胞及网织红细胞生成指数（reticulocyte production index, RPI）水平无显著差异，但IL-6、CRP、铁蛋白、铁调素、TNF-α及GDF15水平显著升高。透析组患者的铁、转铁蛋白、血红蛋白水平、红细胞计数、平均红细胞血红蛋白量（mean cell hemoglobin, MCH）及平均红细胞血红蛋白浓度（mean cell hemoglobin concentration, MCHC）均显著低于对照组。在透析患者亚组中，糖尿病患者的sTfR水平更高；sTfR水平与网织红细胞、红细胞计数、RPI以及促红细胞生成素制剂（erythropoiesis stimulating agents, ESA）治疗剂量、静脉铁剂使用剂量呈显著正相关，而与血清铁、铁蛋白、转铁蛋白饱和度、铁调素、MCH及MCHC呈显著负相关。多元线性回归分析显示，ESA剂量、RPI、血清铁、糖尿病状态及铁调素水平与透析患者的sTfR水平独立相关，进而与红细胞生成过程相关。
<b>结论:</b> 本研究数据表明，除RPI与ESA剂量外，糖尿病状态与铁调素也与透析患者的红细胞生成密切相关。糖尿病对sTfR水平的影响有待进一步研究。