Division of Nephrology, University of California, San Francisco, San Francisco, California, USA.
Kidney Int. 2013 May;83(5):909-14. doi: 10.1038/ki.2012.458. Epub 2013 Jan 23.
Novel biomarkers may improve our ability to predict which patients with chronic kidney disease (CKD) are at higher risk for progressive loss of renal function. Here, we assessed the performance of urine neutrophil gelatinase-associated lipocalin (NGAL) for outcome prediction in a diverse cohort of 3386 patients with CKD in the Chronic Renal Insufficiency Cohort study. In this cohort, the baseline mean estimated glomerular filtration rate (eGFR) was 42.4 ml/min per 1.73 m(2), the median 24-h urine protein was 0.2 g/day, and the median urine NGAL concentration was 17.2 ng/ml. Over an average follow-up of 3.2 years, there were 689 cases in which the eGFR was decreased by half or incident end-stage renal disease developed. Even after accounting for eGFR, proteinuria, and other known CKD progression risk factors, urine NGAL remained a significant independent risk factor (Cox model hazard ratio 1.70 highest to lowest quartile). The association between baseline urine NGAL levels and risk of CKD progression was strongest in the first 2 years of biomarker measurement. Within this time frame, adding urine NGAL to a model that included eGFR, proteinuria, and other CKD progression risk factors led to net reclassification improvement of 24.7%, but the C-statistic remained nearly identical. Thus, while urine NGAL was an independent risk factor of progression among patients with established CKD of diverse etiology, it did not substantially improve prediction of outcome events.
新型生物标志物可能提高我们预测慢性肾脏病(CKD)患者肾功能进行性丧失风险的能力。在这里,我们评估了尿液中性粒细胞明胶酶相关脂质运载蛋白(NGAL)在慢性肾功能不全队列研究中 3386 例不同病因 CKD 患者的预后预测中的表现。在该队列中,基线平均估算肾小球滤过率(eGFR)为 42.4 ml/min/1.73 m²,中位 24 小时尿蛋白为 0.2 g/天,中位尿液 NGAL 浓度为 17.2ng/ml。在平均 3.2 年的随访中,有 689 例患者 eGFR 降低一半或发生终末期肾病。即使考虑到 eGFR、蛋白尿和其他已知的 CKD 进展风险因素,尿液 NGAL 仍然是一个显著的独立风险因素(Cox 模型风险比 1.70,最高到最低四分位数)。在生物标志物测量的前 2 年内,基线尿液 NGAL 水平与 CKD 进展风险之间的相关性最强。在这一时间范围内,将尿液 NGAL 添加到包含 eGFR、蛋白尿和其他 CKD 进展风险因素的模型中,可使净重新分类改善 24.7%,但 C 统计量几乎保持不变。因此,尽管尿液 NGAL 是不同病因 CKD 患者进展的独立风险因素,但它并未显著改善结局事件的预测。