Neutrophil gelatinase-associated lipocalin as a biomarker of acute kidney injury-where do we stand today?
Neutrophil gelatinase-associated lipocalin as a biomarker of acute kidney injury-where do we stand today?
复制标题
DOI：
10.1093/ndt/gfr006
复制
发表时间：
2011-03-01
影响因子：
6.1
通讯作者：
Schmidt-Ott, Kai M.
中科院分区：
文献类型：
--
作者：
Schmidt-Ott, Kai M.
中性粒细胞明胶酶相关脂质运载蛋白 (NGAL) 是称为“肾脏生物标志物”的新一代诊断学的第一个成员，距离进入临床实践可能仅几步之遥。这项新测试测量什么？这是新的“肾脏肌钙蛋白”吗？ NGAL 临床研究最重要的结论是什么？他们有什么局限性？ NGAL 将如何影响临床实践？肾科医生很快就会更频繁地遇到这些问题。因此，在这篇社论中，我们将尝试简要总结 NGAL 领域的现状。 NGAL 是脂质运载蛋白家族的一种 25 kDa 小蛋白，是通过对动物实验性急性肾损伤 (AKI) 诱导的肾脏基因进行全基因组分析而发现的 [1]。 NGAL 是受损肾脏中最上调的基因之一，并且满足有希望的肾小管损伤生物标志物的标准，因为它是一种分泌性肾小管蛋白，在 AKI 发作后迅速进入尿液和血清。值得注意的是，在小鼠缺血再灌注损伤后，可以检测到血液和尿液中 NGAL 水平升高[1]。早期的临床前研究引发了大量且迅速扩大的临床试验，探讨 NGAL 在诊断 AKI 中的效用。对接受体外循环的患者进行的研究表明，发生 AKI 的患者术后 2 小时血浆和尿液 NGAL 水平显着升高 [2, 3]。 NGAL 的增加先于血清肌酐的增加 24-48 小时。在其他临床环境中也观察到 NGAL 水平的类似增加，包括造影剂诱发的 AKI、败血症相关的 AKI 和肾移植后的 AKI [4-7]。此外，多项研究表明，NGAL 水平升高可预测 AKI 的不良临床结果，包括透析开始和死亡率，即使根据肌酐水平等传统预测因素进行调整也是如此 [2, 8–10]。基于小鼠和患者的研究结果，开发了 NGAL 沿肾单位运输的模型（图 1），该模型支持尿液或血清 NGAL 水平作为肾脏损伤生物传感器的概念 [11]。 NGAL 信使 RNA 和蛋白质表达在受损肾小管中显着诱导，导致
Neutrophil gelatinase-associated lipocalin (NGAL) is the first member of a new generation of diagnostics called ‘renal biomarkers’ that may be just a few steps away from entering clinical practice. What does this new test measure? Is this the new ‘troponin for the kidney’? What are the most important conclusions from clinical studies on NGAL? What are their limitations? How will NGAL affect clinical practice? Nephrologists will soon encounter these questions more frequently. Hence, in this editorial, we will attempt to briefly summarize the current state of the NGAL field. NGAL, a small 25-kDa protein of the lipocalin family, was discovered through a genome-wide analysis of kidney genes that are induced in response to experimental acute kidney injury (AKI) in animals [1]. NGAL was among the top upregulated genes in damaged kidneys and fulfilled the criteria of a promising biomarker of tubular damage since it was a secreted tubular protein that entered both urine and serum rapidly after the onset of AKI. Markedly, increased levels of NGAL in blood and urine could be detected following ischaemia-reperfusion injury in mice [1]. The early preclinical studies prompted a large and rapidly expanding body of clinical trials that addressed the utility of NGAL in diagnosing AKI. Studies in patients undergoing cardiopulmonary bypass revealed marked increases of plasma and urinary NGAL levels as early as 2 h after surgery in patients that developed AKI [2, 3]. This increase in NGAL preceded the increase in serum creatinine by 24–48 h. Similar increases in NGAL levels were observed in other clinical settings, including contrast-induced AKI, sepsisassociated AKI and AKI following kidney transplantation [4–7]. Furthermore, several studies suggested that elevated NGAL levels are predictive of poor clinical outcomes in AKI, including dialysis initiation and mortality, even when adjusted for conventional predictors, such as creatinine levels [2, 8–10].Based on findings in mice and patients, a model of NGAL trafficking along the nephron was developed (Figure 1) which supported the concept of urinary or serum NGAL levels as biosensors of kidney damage [11]. NGAL messenger RNA and protein expression are markedly induced in tubules of the damaged kidney, resulting in elevated