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中性粒细胞明胶酶相关脂质运载蛋白:对比剂肾病风险的一个新标志物。

Neutrophil gelatinase-associated lipocalin: a novel marker of contrast nephropathy risk.

机构信息

Section of Cardiology, Department of Medicine, Providence Hospital and Medical Center, St. John Providence Health System, Southfield, William Beaumont Hospital, Royal Oak, and Northern Michigan Hospital, Petoskey, MI 48374, USA.

出版信息

Am J Nephrol. 2012;35(6):509-14. doi: 10.1159/000339163. Epub 2012 May 23.

DOI:10.1159/000339163
PMID:22627273
Abstract

BACKGROUND

Neutrophil gelatinase-associated lipocalin (NGAL, siderocalin) is a protein secreted by the kidney in the setting of acute kidney injury in an attempt to regulate and bind the release of catalytic iron from injured cells. We sought to evaluate the relationships between baseline NGAL, renal filtration function, and the degree of injury reflected by further increases in NGAL.

METHODS

This study was a prospective, blinded assessment of blood samples taken from patients with estimated glomerular filtration rate (eGFR) <75 ml/min/1.73 m(2) undergoing non-urgent coronary angiography and intervention using iodinated contrast. Renal transplant recipients, dialysis patients, and administration of iodinated contrast in the prior 30 days were exclusion criteria. Plasma NGAL was measured using the Alere™ assay. Serum creatinine (Cr) was measured using calibrated methods at a core laboratory. Samples were obtained at baseline, 1, 2, 4, 6, 12, 24, and 48 h after contrast administration.

RESULTS

A total of 63 subjects were enrolled with a mean age of 69.4 ± 9.1 years, 73% male, 35% with diabetes, and a mean eGFR of 47.82 ± 15.46 ml/min/1.73 m(2). The correlation between eGFR and NGAL was r = -0.61, 95% CI -0.74 to -0.44, p < 0.001. When stratified by baseline NGAL tertile, the peak NGAL observed for each group occurred at 29.0 ± 22.2 h and there was a twofold increase in the mean and peak change in NGAL across the tertiles. NGAL began to rise 6 h after contrast exposure and followed a similar course to serum Cr and at 48 h the overall mean NGAL was still rising. Only 2 patients sustained a rise in Cr of >25% or ≥0.5 mg/dl. Multivariate regression revealed that baseline NGAL (p < 0.001) and not eGFR (p = 0.95) was independently associated with the NGAL value at 48 h.

CONCLUSIONS

Baseline NGAL is strongly correlated with eGFR in patients with reduced renal filtration function undergoing coronary angiography. The magnitude of rise in NGAL is positively associated with the baseline value and is analogous to the time course of Cr in blood after contrast exposure. NGAL and not eGFR is an independent predictor of changes in the post-procedure NGAL. A baseline NGAL level is necessary for the interpretation of NGAL levels in the evaluation of acute kidney injury.

摘要

背景

中性粒细胞明胶酶相关脂质运载蛋白(NGAL,铁蛋白)是一种在急性肾损伤情况下由肾脏分泌的蛋白质,试图调节和结合受损细胞中催化铁的释放。我们试图评估基线 NGAL 与肾滤过功能以及 NGAL 进一步升高所反映的损伤程度之间的关系。

方法

本研究是一项前瞻性、盲法评估,对估计肾小球滤过率(eGFR)<75 ml/min/1.73 m²的患者进行非紧急冠状动脉造影和介入治疗,采集血样。排除标准包括肾移植受者、透析患者以及在过去 30 天内使用碘造影剂。使用 Alere™ 检测法测量血浆 NGAL。血清肌酐(Cr)在核心实验室使用校准方法进行测量。在造影剂给药后 1、2、4、6、12、24 和 48 h 采集样本。

结果

共纳入 63 例患者,平均年龄为 69.4±9.1 岁,73%为男性,35%患有糖尿病,平均 eGFR 为 47.82±15.46 ml/min/1.73 m²。eGFR 与 NGAL 之间的相关性为 r =-0.61,95%CI-0.74 至-0.44,p<0.001。按基线 NGAL 三分位分层时,每组观察到的峰值 NGAL 出现在 29.0±22.2 h,三分位组之间 NGAL 的平均和峰值变化增加了两倍。NGAL 在造影剂暴露后 6 h 开始升高,并遵循与血清 Cr 相似的过程,在 48 h 时,总体平均 NGAL 仍在升高。仅 2 例患者的 Cr 升高>25%或≥0.5 mg/dl。多变量回归显示,基线 NGAL(p<0.001)而不是 eGFR(p=0.95)与 48 h 时的 NGAL 值独立相关。

结论

在接受冠状动脉造影的肾滤过功能降低的患者中,基线 NGAL 与 eGFR 密切相关。NGAL 的升高幅度与基线值呈正相关,与造影后血液中 Cr 的时间过程相似。NGAL 而不是 eGFR 是术后 NGAL 变化的独立预测因子。基线 NGAL 水平对于评估急性肾损伤时 NGAL 水平的解释是必要的。

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