Hasegawa Midori, Ishii Junichi, Kitagawa Fumihiko, Takahashi Kazuo, Hayashi Hiroki, Koide Shigehisa, Tomita Makoto, Takahashi Hiroshi, Ozaki Yukio, Yuzawa Yukio
Department of Nephrology, Fujita Health University School of Medicine, 1-98 Dengakugakubo Kutukaek-cho, Toyoake, Aichi, 470-1192, Japan,
Heart Vessels. 2015 Jan;30(1):81-8. doi: 10.1007/s00380-013-0454-7. Epub 2013 Dec 31.
Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular (CV) events. Recently, elevated neutrophil gelatinase-associated lipocalin (NGAL) levels have been reported in patients with heart failure, coronary heart disease, or stroke. Our aim was to assess urinary NGAL as a predictor of CV events in patients with CKD. This was a prospective observational cohort study of 404 patients with predialysis CKD. CV events were defined as CV death, acute coronary syndrome, hospitalization for worsening heart failure, stroke and dissection of aorta. During a mean follow-up period of 33 months, 77 CV events (19.1 %) occurred. After adjustment for gender, age, diabetes, previous cardiovascular disease, urinary albumin/creatinine ratio (UACR), estimated glomerular filtration rate, hemoglobin, and high-sensitivity C-reactive protein, patients with the other quartiles of urinary NGAL had significantly higher risk of CV events compared with patients with the lowest quartile (hazard ratio (HR) 2.81, 95 % confidence interval (CI) 1.01-7.81, P = 0.047 for Q2, HR 3.31, 95 % CI 1.22-9.00, P = 0.019 for Q3, and HR 3.27, 95 % CI 1.15-9.29, P = 0.026 for Q4). Regarding the combination of urinary NGAL with UACR, we also stratified patients into four groups according to whether the level of each marker was above or below the median (61.8 μg per gram creatinine (gCr) for NGAL and 351.1 mg/gCr for UACR). Four-year CV event-free survival rates were 89.2, 79.6, 71.8, and 51.5 % in order for the four respective groups (P < 0.0001). Elevated urinary NGAL was able to predict future CV events in CKD patients, and had incremental predictive value with elevated UACR.
慢性肾脏病（CKD）与心血管（CV）事件风险增加相关。最近，据报道，心力衰竭、冠心病或中风患者的中性粒细胞明胶酶相关脂质运载蛋白（NGAL）水平升高。我们的目的是评估尿NGAL作为CKD患者CV事件的预测指标。这是一项对404例透析前CKD患者进行的前瞻性观察队列研究。CV事件定义为CV死亡、急性冠状动脉综合征、因心力衰竭恶化住院、中风和主动脉夹层。在平均33个月的随访期内，发生了77例CV事件（19.1%）。在对性别、年龄、糖尿病、既往心血管疾病、尿白蛋白/肌酐比值（UACR）、估计肾小球滤过率、血红蛋白和高敏C反应蛋白进行校正后，尿NGAL其他四分位数的患者与最低四分位数的患者相比，CV事件风险显著更高（第二四分位数的风险比（HR）为2.81，95%置信区间（CI）为1.01-7.81，P=0.047；第三四分位数的HR为3.31，95%CI为1.22-9.00，P=0.019；第四四分位数的HR为3.27，95%CI为1.15-9.29，P=0.026）。关于尿NGAL与UACR的联合情况，我们还根据每个标志物水平高于或低于中位数（NGAL为每克肌酐（gCr）61.8μg，UACR为351.1mg/gCr）将患者分为四组。四组患者的四年无CV事件生存率分别为89.2%、79.6%、71.8%和51.5%（P<0.0001）。尿NGAL升高能够预测CKD患者未来的CV事件，并且与UACR升高具有增量预测价值。
