Department of Nephrology and Hypertension, Internal Medicine, St. Marianna University School of Medicine, Kanagawa, Japan; Department of Anatomy, St. Marianna University School of Medicine, Kanagawa, Japan.
Clin Chim Acta. 2013 Sep 23;424:104-8. doi: 10.1016/j.cca.2013.05.020. Epub 2013 May 30.
Deterioration of diabetic nephropathy (DN) is largely determined by the degree of tubulointerstitial changes rather than the extent of histological changes in the glomeruli. Therefore, a tubular marker that accurately reflects tubulointerstitial damage may be an excellent biomarker for early detection or prediction of DN. Liver-type fatty-acid binding protein (L-FABP) is a 14 kDa small molecule that is expressed in the cytoplasm of human proximal tubules. In vivo experimental studies revealed that renal L-FABP gene expression was up-regulated by various stresses that cause tubulointerstitial damage, such as massive proteinuria, hyperglycemia, hypertension, ischemia and toxins, and that urinary excretion of L-FABP was increased. Recent clinical studies of patients with type 1 or type 2 diabetes demonstrated that urinary excretion of L-FABP derived from proximal tubules is a suitable biomarker for predicting and monitoring deterioration of renal function in DN. Moreover, therapeutic interventions with renoprotective effects reduced urinary L-FABP concentrations. Therefore, urinary L-FABP measured using the Human L-FABP ELISA Kit developed by CMIC Co., Ltd. (Tokyo, Japan) was confirmed as a newly established tubular biomarker by the Ministry of Health, Labour and Welfare in Japan in 2010. This review article summarizes the clinical significance of urinary L-FABP in DN.
糖尿病肾病 (DN) 的恶化在很大程度上取决于肾小管间质变化的程度,而不是肾小球的组织学变化程度。因此,一种能准确反映肾小管间质损伤的小管标志物可能是早期发现或预测 DN 的极好的生物标志物。肝型脂肪酸结合蛋白 (L-FABP) 是一种 14kDa 的小分子,在人近端小管的细胞质中表达。体内实验研究表明,肾脏 L-FABP 基因表达在各种导致肾小管间质损伤的应激下被上调,如大量蛋白尿、高血糖、高血压、缺血和毒素,并且 L-FABP 的尿排泄增加。最近对 1 型或 2 型糖尿病患者的临床研究表明,源自近端小管的尿 L-FABP 排泄是预测和监测 DN 肾功能恶化的合适生物标志物。此外,具有肾脏保护作用的治疗干预措施降低了尿 L-FABP 浓度。因此,日本厚生劳动省在 2010 年确认使用日本 CMIC 株式会社 (东京) 开发的 Human L-FABP ELISA Kit 测量的尿 L-FABP 是一种新建立的小管生物标志物。这篇综述文章总结了尿 L-FABP 在 DN 中的临床意义。