BRIGHTEN研究基于属性的交叉分类分析表明,促红细胞生成素刺激剂的治疗反应性可预测肾性贫血的心肺肾预后。
Attribute based cross classification analyses from the BRIGHTEN study reveal that therapeutic responsiveness to erythropoiesis stimulating agents predicts cardiorenal prognosis in renal anemia.
作者信息
Kataoka Hiroshi, Hayashi Terumasa, Nangaku Masaomi, Narita Ichiei, Kagimura Tatsuo, Nitta Kosaku, Hoshino Junichi
机构信息
Department of Nephrology, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan.
Department of Clinical Engineering, Faculty of Human Care at Makuhari, Tohto University, Chiba, Japan.
出版信息
Sci Rep. 2025 Jul 2;15(1):23221. doi: 10.1038/s41598-025-05762-y.
Renal anemia outcomes are influenced by sex and age; however, current guidelines for renal anemia lack sex- or age-specific standards for initiating treatment. Recently, the concept of attribute-based medicine has gained attention, with an emphasis on personalized approaches based on patient characteristics. As prognostic factors for renal and cardiovascular outcomes may vary between men and women, as well as between younger and older patients with chronic kidney disease (CKD), we aimed to investigate anemia treatment-related indicators influencing kidney disease progression and cardiovascular events across four age and sex attributes (cross-classified by sex and age < or ≥ 65 years). A total of 1,671 patients with CKD and renal anemia from the BRIGHTEN study, who were initiated on an erythropoiesis-stimulating agent (ESA) according to Japanese guidelines for renal anemia recommending initiating treatment when the hemoglobin (Hb) level is 11 g/dL), were analyzed using the ESA resistance index-1B (ERI-1B) and the initial ESA response index (iEResI). Baseline Hb levels were similar across all sub-groups (9.7-9.9 g/dL), and kidney function was lowest in younger men (estimated glomerular filtration rate, 15.6 ml/min/1.73 m) and highest in older women (estimated glomerular filtration rate, 19.4 ml/min/1.73 m). Darbepoetin alfa doses during 12 weeks were lowest in younger men (0.79 μg/kg) and highest in older women (1.08 μg/kg). Renal outcomes were the poorest in younger men and the best in older women. Cardiovascular outcomes were the poorest in older men and the best in younger women. Multivariable Cox analyses showed that baseline hemoglobin levels (hazard ratio [HR], 0.77; P < 0.001) and the iEResI (HR, 0.76; P < 0.001) were associated with kidney prognosis across the cohort, whereas ERI-1B was not. When stratified by cross-classification, kidney prognosis correlated with iEResI (HR, 0.63; P = 0.019) in younger men and with ERI-1B (HR, 1.10; P < 0.001) in older women. Renal outcomes were linked to hemoglobin levels and ESA responsiveness in younger men with the poorest outcomes and to ESA resistance in older women with the best outcomes. This study revealed that renal outcomes correlated with Hb levels and ESA responsiveness in patients with CKD and anemia, especially in younger men with poor renal outcomes and with ESA resistance in older women with the best renal outcomes. Cross-classification helps identify specific patient attributes that should be targeted for optimizing anemia treatment in CKD.
肾性贫血的结局受性别和年龄影响;然而,目前的肾性贫血指南缺乏针对启动治疗的性别或年龄特异性标准。最近,基于属性的医学概念受到关注,强调基于患者特征的个性化方法。由于肾和心血管结局的预后因素在男性和女性之间以及慢性肾脏病(CKD)的年轻和老年患者之间可能有所不同,我们旨在研究影响肾脏病进展和心血管事件的贫血治疗相关指标,涉及四个年龄和性别属性(按性别和年龄<或≥65岁交叉分类)。对来自BRIGHTEN研究的1671例CKD和肾性贫血患者进行了分析,这些患者根据日本肾性贫血指南在血红蛋白(Hb)水平为11 g/dL时开始使用促红细胞生成素(ESA),使用ESA抵抗指数-1B(ERI-1B)和初始ESA反应指数(iEResI)进行分析。所有亚组的基线Hb水平相似(9.7-9.9 g/dL),年轻男性的肾功能最低(估计肾小球滤过率,15.6 ml/min/1.73 m²),老年女性的肾功能最高(估计肾小球滤过率,19.4 ml/min/1.73 m²)。12周内的达比加群酯剂量在年轻男性中最低(0.79 μg/kg),在老年女性中最高(1.08 μg/kg)。肾脏结局在年轻男性中最差,在老年女性中最好。心血管结局在老年男性中最差,在年轻女性中最好。多变量Cox分析显示,基线血红蛋白水平(风险比[HR],0.77;P<0.001)和iEResI(HR,0.76;P<0.001)与整个队列的肾脏预后相关,而ERI-1B则不相关。按交叉分类分层时,年轻男性的肾脏预后与iEResI相关(HR,0.63;P = 0.019),老年女性的肾脏预后与ERI-1B相关(HR,1.10;P<0.001)。肾脏结局与结局最差的年轻男性的血红蛋白水平和ESA反应性以及结局最好的老年女性的ESA抵抗相关。这项研究表明,CKD和贫血患者的肾脏结局与Hb水平和ESA反应性相关,尤其是结局较差的年轻男性以及结局最好的老年女性中的ESA抵抗。交叉分类有助于识别在CKD中优化贫血治疗应针对的特定患者属性。