Allory Y, Audard V, Fontanges P, Ronco P, Debiec H
INSERM UMR S 702, Paris, France.
Kidney Int. 2008 Mar;73(6):751-8. doi: 10.1038/sj.ki.5002640. Epub 2007 Dec 5.
The L1 cell adhesion molecule (CD171) is a multidomain membrane glycoprotein of the immunoglobulin superfamily. We evaluated its expression in human acute kidney injury and assessed its use as a tissue and urinary marker of acute tubular injury. Using immunohistochemical studies with antibodies to the extracellular or cytoplasmic domains, we compared L1 expression in normal kidneys in 24 biopsies taken from patients with acute tubular necrosis. L1 was found at the basolateral and the lateral membrane in all epithelial cells of the collecting duct in the normal kidney except for intercalated cells. In acute tubular necrosis, L1 lost its polarized distribution being found in both the basolateral and apical domains of the collecting duct. Further, it was induced in thick ascending limb and distal tubule cells. Apically expressed L1 found only when the cytoplasmic domain antibody was used in biopsy specimens of patients with acute tubular necrosis. The levels of urinary L1, normalized for creatinine, were significantly higher in all 24 patients with acute tubular necrosis compared to five patients with prerenal azotemia or to six patients with other causes of acute kidney injury. Our study shows that a soluble form of human L1 can be detected in the urine of patients with acute tubular necrosis and that this may be a marker of distal nephron injury.
L1细胞黏附分子(CD171)是免疫球蛋白超家族的一种多结构域膜糖蛋白。我们评估了其在人类急性肾损伤中的表达,并评估了其作为急性肾小管损伤的组织和尿液标志物的用途。通过使用针对细胞外或细胞质结构域的抗体进行免疫组织化学研究,我们比较了从急性肾小管坏死患者获取的24份活检标本中正常肾脏的L1表达。在正常肾脏中,除闰细胞外,集合管所有上皮细胞的基底外侧和侧膜均发现有L1。在急性肾小管坏死中,L1失去其极性分布,在集合管的基底外侧和顶端结构域均有发现。此外,它在髓袢升支粗段和远曲小管细胞中被诱导表达。仅在使用细胞质结构域抗体检测急性肾小管坏死患者的活检标本时,才发现顶端表达的L1。与5例肾前性氮质血症患者或6例其他原因导致急性肾损伤的患者相比,所有24例急性肾小管坏死患者经肌酐校正后的尿L1水平均显著更高。我们的研究表明,在急性肾小管坏死患者的尿液中可检测到可溶性人L1,这可能是远端肾单位损伤的一个标志物。