Ding Hanlu, He Yani, Li Kailong, Yang Jurong, Li Xiaolin, Lu Rong, Gao Wenda
Department of Nephrology, Daping Hospital, The Third Military Medical University, Chongqing 40038, PR China.
Clin Immunol. 2007 May;123(2):227-34. doi: 10.1016/j.clim.2007.01.010. Epub 2007 Mar 13.
Renal tubulointerstitial injury plays an important role in the development of IgA nephropathy (IgAN), the most common form of glomerulonephritis. Few currently in use biomarkers can sensitively detect the earliest signs of renal tubular injury, hindering our efforts to launch preventive and therapeutic measures for this disorder in a timely manner. Neutrophil gelatinase-associated lipocalin (NGAL) is an acute phase protein that is rapidly released from not only neutrophils but also a variety of cell types upon inflammation and tissue injury. Its small molecular size and protease resistance could render it an excellent biomarker of renal injury in IgAN. In this study, we tested this hypothesis by measuring urinary levels of NGAL, creatinine and N-acetyl-beta-D-glucosaminidase (NAG) in 40 healthy individuals and 70 IgAN patients with various disease severities. The urinary NGAL levels and NGAL/creatinine values were significantly upregulated in Lee grade III IgAN patients, in correlation with progressive glomerular mesangial proliferation and tubulointerstitial injury. Compared with urinary NAG levels, the urinary NGAL levels elevated much more drastically and can be readily detected even in Lee grade II IgAN patients when their NAG levels showed almost no change. Our findings suggest the promising use of urinary NGAL as an early biomarker for tubulointerstitial injury of IgA nephropathy and perhaps other types of renal disease in general.
肾小管间质损伤在IgA肾病（IgAN）的发展过程中起着重要作用，IgA肾病是肾小球肾炎最常见的形式。目前使用的生物标志物中，很少有能灵敏检测肾小管损伤最早迹象的，这阻碍了我们及时开展针对该疾病的预防和治疗措施。中性粒细胞明胶酶相关脂质运载蛋白（NGAL）是一种急性期蛋白，在炎症和组织损伤时不仅从中性粒细胞，还从多种细胞类型中迅速释放。其小分子大小和蛋白酶抗性使其可能成为IgA肾病肾损伤的优秀生物标志物。在本研究中，我们通过测量40名健康个体和70名不同疾病严重程度的IgA肾病患者尿液中的NGAL、肌酐和N-乙酰-β-D-氨基葡萄糖苷酶（NAG）水平来验证这一假设。Lee III级IgA肾病患者的尿NGAL水平和NGAL/肌酐值显著上调，与肾小球系膜渐进性增生和肾小管间质损伤相关。与尿NAG水平相比，尿NGAL水平升高更为显著，即使在Lee II级IgA肾病患者中，当他们的NAG水平几乎没有变化时，也能很容易检测到尿NGAL水平升高。我们的研究结果表明，尿NGAL有望作为IgA肾病以及可能其他类型肾病肾小管间质损伤的早期生物标志物。
