Steno Diabetes Center Copenhagen, Niels Steensens Vej 2, 2820, Gentofte, Denmark.
Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Acta Diabetol. 2018 Nov;55(11):1143-1150. doi: 10.1007/s00592-018-1205-0. Epub 2018 Aug 14.
AIMS: Urinary levels of kidney injury molecule 1 (u-KIM-1) and neutrophil gelatinase-associated lipocalin (u-NGAL) reflect proximal tubular pathophysiology and have been proposed as risk markers for development of complications in patients with type 2 diabetes (T2D). We clarify the predictive value of u-KIM-1 and u-NGAL for decline in eGFR, cardiovascular events (CVE) and all-cause mortality in patients with T2D and persistent microalbuminuria without clinical cardiovascular disease. METHODS: This is a prospective study that included 200 patients. u-KIM-1 and u-NGAL were measured at baseline and were available in 192 patients. Endpoints comprised: decline in eGFR > 30%, a composite of fatal and nonfatal CVE consisting of: cardiovascular mortality, myocardial infarction, stroke, ischemic heart disease and heart failure based on national hospital discharge registries, and all-cause mortality. Adjusted Cox models included traditional risk factors, including eGFR. Hazard ratios (HR) are provided per 1 standard deviation (SD) increment of log2-transformed values. Relative integrated discrimination improvement (rIDI) was calculated. RESULTS: During the 6.1 years' follow-up, higher u-KIM-1 was a predictor of eGFR decline (n = 29), CVE (n = 34) and all-cause mortality (n = 29) in adjusted models: HR (95% CI) 1.68 (1.04-2.71), p = 0.034; 2.26 (1.24-4.15), p = 0.008; and 1.52 (1.00-2.31), p = 0.049. u-KIM-1 contributed significantly to risk prediction for all-cause mortality evaluated by rIDI (63.1%, p = 0.001). u-NGAL was not a predictor of any of the outcomes after adjustment. CONCLUSIONS: In patients with T2D and persistent microalbuminuria, u-KIM-1, but not u-NGAL, was an independent risk factor for decline in eGFR, CVE and all-cause mortality, and contributed significant discrimination for all-cause mortality, beyond traditional risk factors.
目的:尿肾损伤分子 1(u-KIM-1)和中性粒细胞明胶酶相关脂质运载蛋白(u-NGAL)的水平反映了近端肾小管的病理生理学变化,并已被提议作为 2 型糖尿病(T2D)患者发生并发症的风险标志物。我们澄清了 u-KIM-1 和 u-NGAL 对 T2D 患者持续微量白蛋白尿且无临床心血管疾病患者的 eGFR 下降、心血管事件(CVE)和全因死亡率的预测价值。
方法:这是一项前瞻性研究,纳入了 200 名患者。在基线时测量了 u-KIM-1 和 u-NGAL,192 名患者可获得这两种标志物的数据。终点包括:eGFR 下降>30%,致命和非致命 CVE 的综合指标,包括心血管死亡率、心肌梗死、中风、缺血性心脏病和心力衰竭,基于国家医院出院登记处,以及全因死亡率。调整后的 Cox 模型包括传统的危险因素,包括 eGFR。每增加 1 个标准差(SD)的对数转换值,风险比(HR)都会提供。计算相对综合判别改善(rIDI)。
结果:在 6.1 年的随访期间,较高的 u-KIM-1 在调整后的模型中是 eGFR 下降(n=29)、CVE(n=34)和全因死亡率(n=29)的预测因素:HR(95%CI)为 1.68(1.04-2.71),p=0.034;2.26(1.24-4.15),p=0.008;和 1.52(1.00-2.31),p=0.049。u-KIM-1 通过 rIDI(63.1%,p=0.001)对全因死亡率的风险预测有显著贡献。调整后,u-NGAL 不是任何结果的预测因素。
结论:在 T2D 合并持续微量白蛋白尿的患者中,u-KIM-1 是 eGFR 下降、CVE 和全因死亡率的独立危险因素,与传统危险因素相比,对全因死亡率的判别能力有显著提高。
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