Uchida Yushi, Nakano Toshiaki, Kitamura Hiromasa, Taniguchi Masatomo, Tsuruya Kazuhiko, Kitazono Takanari
Division of Internal Medicine, Fukuoka Dental College, Fukuoka, Japan.
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.
Clin Exp Nephrol. 2023 Jan;27(1):79-88. doi: 10.1007/s10157-022-02278-x. Epub 2022 Sep 13.
Hyporesponsiveness to erythropoiesis-stimulating agents (ESAs) is associated with increased risks of all cause and cardiovascular mortality in patients undergoing hemodialysis (HD). However, the impact of the hematopoietic response to ESAs on the development of stroke, including brain hemorrhage and infarction, remains unclear.
In total, 2886 patients undergoing maintenance HD registered in the Q-Cohort Study who were treated with ESAs were prospectively followed up for 4 years. The hematopoietic response to ESAs was evaluated by the erythropoietin resistance index (ERI), calculated by dividing the weekly dose of ESA by post-HD weight and hemoglobin (U/kg/week/g/dL). The primary outcomes were the incidences of brain hemorrhage and infarction. Patients were divided into quartiles based on their ERI at baseline (Q1, ≤ 4.1; Q2, 4.2-7.0; Q3, 7.1-11.2; and Q4, ≥ 11.3). The risks of brain hemorrhage and infarction were estimated using Cox proportional hazards models, adjusting for potential confounders.
During the 4 year follow-up period, 71 patients developed brain hemorrhage and 116 developed brain infarction. In the multivariable analysis, the incidence of brain hemorrhage in the highest quartile (Q4) was significantly higher than that in the lowest quartile (Q1) (hazard ratio [95% confidence interval], 2.18 [1.08-4.42]). However, the association between the ERI and the incidence of brain infarction was not significant.
A higher ERI was associated with an increased risk of brain hemorrhage, but not brain infarction, in patients undergoing maintenance HD. A high ERI is thus an important risk factor for brain hemorrhage in these patients.
对促红细胞生成素（ESA）反应低下与血液透析（HD）患者全因死亡和心血管死亡风险增加相关。然而，ESA对造血的反应对包括脑出血和梗死在内的中风发生发展的影响仍不清楚。
共有2886例在Q队列研究中登记的接受维持性HD治疗且接受ESA治疗的患者进行了4年的前瞻性随访。通过促红细胞生成素抵抗指数（ERI）评估对ESA的造血反应，ERI通过将ESA的每周剂量除以后续透析体重和血红蛋白来计算（U/kg/周/g/dL）。主要结局是脑出血和梗死的发生率。根据患者基线时的ERI将其分为四分位数（Q1，≤4.1；Q2，4.2 - 7.0；Q3，7.1 - 11.2；Q4，≥11.3）。使用Cox比例风险模型估计脑出血和梗死的风险，并对潜在混杂因素进行校正。
在4年随访期间，71例患者发生脑出血，116例发生脑梗死。在多变量分析中，最高四分位数（Q4）组的脑出血发生率显著高于最低四分位数（Q1）组（风险比[95%置信区间]，2.18[1.08 - 4.42]）。然而，ERI与脑梗死发生率之间的关联不显著。
在接受维持性HD治疗的患者中，较高的ERI与脑出血风险增加相关，但与脑梗死无关。因此，高ERI是这些患者脑出血的重要危险因素。
