Abstract:
Acute and chronic kidney diseases are an evolving continuum for which reliable biomarkers of early disease are lacking. The potential use of glycosidases, enzymes involved in carbohydrate metabolism, in kidney disease detection has been under investigation since the 1960s. N-acetyl-beta-D-glucosaminidase (NAG) is a glycosidase commonly found in proximal tubule epithelial cells (PTECs). Due to its large molecular weight, plasma-soluble NAG cannot pass the glomerular filtration barrier; thus, increased urinary concentration of NAG (uNAG) may suggest injury to the proximal tubule. As the PTECs are the workhorses of the kidney that perform much of the filtration and reabsorption, they are a common starting point in acute and chronic kidney disease. NAG has previously been researched, and it is widely used as a valuable biomarker in both acute and chronic kidney disease, as well as in patients suffering from diabetes mellitus, heart failure, and other chronic diseases leading to kidney failure. Here, we present an overview of the research pertaining to uNAG\'s biomarker potential across the spectrum of kidney disease, with an additional emphasis on environmental nephrotoxic substance exposure. In spite of a large body of evidence strongly suggesting connections between uNAG levels and multiple kidney pathologies, focused clinical validation tests and knowledge on underlining molecular mechanisms are largely lacking.
摘要:
急性和慢性肾脏疾病是一个不断发展的连续体,缺乏可靠的早期疾病生物标志物。糖苷酶的潜在用途,参与碳水化合物代谢的酶,自1960年代以来,肾脏疾病的检测一直在调查中。N-乙酰-β-D-氨基葡萄糖苷酶(NAG)是一种常见于近端小管上皮细胞(PTEC)的糖苷酶。由于其分子量大,血浆可溶性NAG不能通过肾小球滤过屏障;因此,尿NAG(uNAG)浓度升高可能提示近端小管损伤。由于PTEC是肾脏的主力,可以进行大部分过滤和重吸收,它们是急性和慢性肾脏疾病的共同起点。NAG以前曾被研究过,它被广泛用作急性和慢性肾脏疾病的有价值的生物标志物,以及患有糖尿病的患者,心力衰竭,和其他导致肾衰竭的慢性疾病。这里,我们概述了与uNAG在肾脏疾病谱中的生物标志物潜力有关的研究,另外强调环境肾毒性物质的暴露。尽管大量证据强烈表明uNAG水平与多种肾脏病理之间存在联系,在很大程度上缺乏集中的临床验证测试和强调分子机制的知识。