Supplementary Material for: Endogenous Erythropoietin and Hepatic Dysfunction in Acute Kidney Injury Requiring Renal Replacement Therapy

Backgrounds/Objectives: Elevated erythropoietin (EPO) is observed in human acute kidney injury (AKI). Whether blood EPO level is associated with mortality or other organ dysfunction in critically ill patients is unknown. Methods: A prospective observational cohort study of 162 AKI patients requiring renal replacement therapy (RRT) was conducted in our intensive care unit (ICU) during October 2013 through October 2016. We evaluated the relation with plasma EPO at RRT initiation and 90-day mortality, hemoglobin, urine output, and sequential organ failure assessment (SOFA) score until day 7 or discharge from the ICU. Results: The analysis revealed that EPO was significantly associated with 90-day mortality with an adjusted hazard ratio of 2.13 (95% CI 1.11–5.78). Hemoglobin levels, RRT dependence, and daily urine output on days 1 through 7 did not differ between the high EPO group (≥56.2 mIU/mL) and low EPO groups (< 56.2 mIU/mL). As for organ dysfunction, hyperbilirubinemia patients (≥2.0 mg/dL; hepatic SOFA ≥2) were more frequent in the high EPO group (62.1 vs. 37.9%; p < 0.05), while other SOFA scores did not differ between both groups. Exacerbation of hepatic dysfunction was observed more frequently in the high EPO than the low EPO group (49.3 vs. 27.2%; p < 0.05). Conclusion: Elevated EPO was not associated with anemia or RRT dependence. However, higher rates of mortality and hepatic dysfunction were observed in high EPO patients than in low EPO patients.研究背景与目的：人类急性肾损伤（AKI，acute kidney injury）患者体内可检测到促红细胞生成素（EPO，erythropoietin）水平升高。目前尚不明确血液EPO水平是否与重症患者的死亡率或其他器官功能障碍存在关联。 方法：本研究于2013年10月至2016年10月期间，在本院重症监护病房（ICU，intensive care unit）开展一项前瞻性观察队列研究，共纳入162例需接受肾脏替代治疗（RRT，renal replacement therapy）的AKI患者。我们评估了患者在开始RRT时的血浆EPO水平与90天死亡率、血红蛋白水平、尿量以及直至入院第7天或转出ICU时的序贯器官衰竭评分（SOFA，sequential organ failure assessment）之间的关联。 结果：分析结果显示，EPO水平与90天死亡率存在显著关联，校正后的风险比（hazard ratio）为2.13（95%置信区间（confidence interval，CI）：1.11~5.78）。高EPO组（≥56.2 mIU/mL）与低EPO组（<56.2 mIU/mL）患者的血红蛋白水平、RRT依赖情况以及第1至7天的每日尿量均无显著差异。在器官功能障碍方面，高EPO组高胆红素血症患者（≥2.0 mg/dL；肝脏SOFA评分≥2）的占比更高（62.1% vs. 37.9%；p<0.05），其余SOFA评分在两组间无显著差异。高EPO组肝功能恶化的发生率显著高于低EPO组（49.3% vs. 27.2%；p<0.05）。 结论：血浆EPO水平升高与贫血或RRT依赖无显著关联。然而，高EPO水平患者的死亡率及肝功能障碍发生率均显著高于低EPO水平患者。