Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli, proximal tubules, and distal nephrons
Urinary neutrophil gelatinase-associated lipocalin levels reflect damage to glomeruli, proximal tubules, and distal nephrons
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DOI：
10.1038/ki.2008.499
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发表时间：
2009-02-01
影响因子：
19.6
通讯作者：
Nakao, Kazuwa
中科院分区：
文献类型：
--
作者：
Kuwabara, Takashige;Mori, Kiyoshi;Nakao, Kazuwa
尿中性粒细胞明胶酶相关脂质运载蛋白（Ngal或脂质运载蛋白2）是肾损伤的非常早期和敏感的生物标志物。在这里，我们确定了Ngal出现在几个实验和临床相关的肾脏疾病的起源和时间过程。在脂肪萎缩和链脲佐菌素诱导的糖尿病肾病小鼠模型中，发现尿Ngal水平显著升高。在后者小鼠中，血管紧张素受体阻滞剂坎地沙坦显著降低尿Ngal排泄。在链脲佐菌素诱导的糖尿病小鼠中，近端小管对Ngal的重吸收严重减少，但与对照小鼠相比，其mRNA和蛋白在肾脏中的上调可以忽略不计，这表明尿Ngal增加主要是由于肾脏重吸收受损。在单侧输尿管梗阻的小鼠模型中，Ngal蛋白合成在Henle扩张的粗升支中显著增加，并且在结扎肾的肿胀肾盂中存在的尿液中发现N。5例肾病综合征或间质性肾炎患者在就诊时尿Ngal水平明显升高，但治疗后这些水平降低。我们的研究表明，尿Ngal水平可能有助于监测反映肾小球滤过屏障、近端小管重吸收和远端肾单位缺陷的各种肾脏疾病的状态和治疗。
Urinary neutrophil gelatinase-associated lipocalin (Ngal or lipocalin 2) is a very early and sensitive biomarker of kidney injury. Here we determined the origin and time course of Ngal appearance in several experimental and clinically relevant renal diseases. Urinary Ngal levels were found to be markedly increased in lipoatrophic-and streptozotocin-induced mouse models of diabetic nephropathy. In the latter mice, the angiotensin receptor blocker candesartan dramatically decreased urinary Ngal excretion. The reabsorption of Ngal by the proximal tubule was severely reduced in streptozotocin-induced diabetic mice, but upregulation of its mRNA and protein in the kidney was negligible, compared to those of control mice, suggesting that increased urinary Ngal was mainly due to impaired renal reabsorption. In the mouse model of unilateral ureteral obstruction, Ngal protein synthesis was dramatically increased in the dilated thick ascending limb of Henle and N was found in the urine present in the swollen pelvis of the ligated kidney. Five patients with nephrotic syndrome or interstitial nephritis had markedly elevated urinary Ngal levels at presentation, but these decreased in response to treatment. Our study shows that the urinary Ngal level may be useful for monitoring the status and treatment of diverse renal diseases reflecting defects in glomerular filtration barrier, proximal tubule reabsorption, and distal nephrons.