Iwasaki Keiichiro, Miyoshi Toru, Urabe Chikara, Sakuragi Satoru, Kawai Yusuke, Fuke Soichiro, Doi Masayuki, Takaishi Atsushi, Oka Takefumi, Tokunaga Naoto, Ito Hiroshi
Department of Cardiovascular Medicine, Okayama University Institute of Academic and Research, Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Department of Cardiovascular Medicine, Iwakuni Clinical Center, Iwakuni 740-8510, Japan.
J Clin Med. 2024 Jul 26;13(15):4384. doi: 10.3390/jcm13154384.
Indoxyl sulfate, a uremic toxin, is associated with mortality and cardiovascular events in patients with chronic kidney disease (CKD). This study aimed to evaluate the prognostic implications of serum indoxyl sulfate levels in patients with heart failure and CKD. This was a prospective multicenter observational study. Overall, 300 patients with chronic heart failure with a previous history of hospitalization and an estimated glomerular filtration rate (eGFR) of 45 mL/min/1.73 m or less (CKD stage G3b to G5) without dialysis were analyzed. The primary outcome assessed in a time-to-event analysis from the measurement of indoxyl sulfate was a composite of all-cause death, hospitalization for heart failure, nonfatal myocardial infarction, and nonfatal stroke. Clinical events were followed-up to one year after indoxyl sulfate measurement. The median patient age was 75 years, and 57% of the patients were men. We divided the cohort into low and high indoxyl sulfate categories according to a median value of 9.63 mg/mL. The primary outcome occurred in 27 of 150 patients (18.0%) in the low indoxyl sulfate group and 27 of 150 patients (18.0%) in the high indoxyl sulfate group (hazard ratio, 1.00; 95% confidence interval, 0.58 to 1.70, = 0.99). In the post hoc exploratory analyses, the results were consistent across age, sex, body mass index, left ventricular ejection fraction, eGFR, and N-terminal pro b-type natriuretic peptide. Among heart failure patients with CKD stages G3b to 5G, serum indoxyl sulfate concentrations were not significantly associated with the subsequent occurrence of cardiovascular events.
硫酸吲哚酚是一种尿毒症毒素，与慢性肾脏病（CKD）患者的死亡率及心血管事件相关。本研究旨在评估血清硫酸吲哚酚水平对心力衰竭合并CKD患者的预后影响。这是一项前瞻性多中心观察性研究。共分析了300例有过住院史、估计肾小球滤过率（eGFR）为45 mL/min/1.73 m²或更低（CKD G3b至G5期）且未接受透析的慢性心力衰竭患者。从测定硫酸吲哚酚开始进行事件发生时间分析，评估的主要结局为全因死亡、因心力衰竭住院、非致死性心肌梗死和非致死性卒中的复合结局。在测定硫酸吲哚酚后对临床事件进行了为期一年的随访。患者中位年龄为75岁，57%为男性。我们根据9.63 mg/mL的中位值将队列分为硫酸吲哚酚低水平组和高水平组。硫酸吲哚酚低水平组150例患者中有27例（18.0%）发生主要结局，硫酸吲哚酚高水平组150例患者中有27例（18.0%）发生主要结局（风险比为1.00；95%置信区间为0.58至1.70，P = 0.99）。在事后探索性分析中，年龄、性别、体重指数、左心室射血分数、eGFR和N末端B型利钠肽原的结果均一致。在CKD G3b至5G期的心力衰竭患者中，血清硫酸吲哚酚浓度与随后发生的心血管事件无显著相关性。
