Kuragano Takahiro, Kitamura Kenichiro, Matsumura Osamu, Matsuda Akihiko, Hara Taiga, Kiyomoto Hideyasu, Murata Toshiaki, Fujimoto Shouichi, Hase Hiroki, Joki Nobuhiko, Fukatsu Atushi, Inoue Toru, Itakura Yukihiro, Nakanishi Takeshi
Department of Internal Medicine, Division of Kidney and Dialysis, Hyogo College of Medicine, Nishinomiya, Japan.
The Third Department of Internal Medicine Faculty of Medicine, The University of Yamanashi, Chuo, Japan.
PLoS One. 2016 Mar 2;11(3):e0147328. doi: 10.1371/journal.pone.0147328. eCollection 2016.
It has been reported that hyporesponsiveness to erythropoiesis-stimulating agent (ESA) is associated with adverse events in patients on maintenance hemodialysis (MHD). However, it has not been determined whether higher iron storage is associated with an improved response, including better survival, to ESA.
We measured serum ferritin, hemoglobin (Hb), and transferrin saturation (TSAT) levels every three months for two years in 1,095 MHD patients. The weekly dose of ESA to Hb ratio was also calculated as an index of ESA responsiveness (ERI).
A significant correlation (p<0.001, R = 0.89) between ferritin and Hb was only observed in the patients with ferritin levels <50 ng/mL. High-dose (≥50 mg/week) intravenous iron administration, female sex, low serum albumin, and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker use were significant predictors of a high ERI value (>280); however, serum ferritin and TSAT levels did not predict a higher ERI. In the time-dependent Cox hazard model, the risk for a composite event in the patients with a high ERI (≥280) and a high ferritin level (≥100 ng/mL) was significantly greater (hazard ratio [HR], 2.09, P = 0.033) than that for patients with a high ERI and a low ferritin (<100 ng/mL) level.
Hb was dependent upon ferritin levels in patients with ferritin levels <50 ng/mL but not in patients with ferritin levels ≥50 ng/mL. Patients with hyporesponsiveness to ESA had a greater risk of composite events, but ERI was unrelated to iron storage.
据报道,对促红细胞生成素(ESA)反应低下与维持性血液透析(MHD)患者的不良事件相关。然而,尚未确定较高的铁储存是否与对ESA的反应改善相关,包括更好的生存率。
我们对1095例MHD患者进行了为期两年的研究,每三个月测量一次血清铁蛋白、血红蛋白(Hb)和转铁蛋白饱和度(TSAT)水平。还计算了ESA每周剂量与Hb的比值作为ESA反应性(ERI)指标。
仅在铁蛋白水平<50 ng/mL的患者中观察到铁蛋白与Hb之间存在显著相关性(p<0.001,R = 0.89)。高剂量(≥50 mg/周)静脉注射铁剂、女性、低血清白蛋白以及使用血管紧张素转换酶抑制剂/血管紧张素受体阻滞剂是ERI值高(>280) 的显著预测因素;然而,血清铁蛋白和TSAT水平并不能预测更高的ERI。在时间依赖性Cox风险模型中,ERI高(≥280)且铁蛋白水平高(≥100 ng/mL)的患者发生复合事件的风险显著高于ERI高且铁蛋白水平低(<100 ng/mL)的患者(风险比[HR],2.09,P = 0.033)。
铁蛋白水平<50 ng/mL的患者中Hb依赖于铁蛋白水平,但铁蛋白水平≥50 ng/mL的患者并非如此。对ESA反应低下的患者发生复合事件的风险更高,但ERI与铁储存无关。