Kamijo-Ikemori Atsuko, Ichikawa Daisuke, Matsui Katsuomi, Yokoyama Takeshi, Sugaya Takeshi, Kimura Kenjiro
Department of Nephrology and Hypertension, St. Marianna University School of Medicine, Kawasaki 261-8511, Japan.
Rinsho Byori. 2013 Jul;61(7):635-40.
Liver-type fatty acid binding protein (L-FABP) is a 14kDa protein found in the cytoplasm of human renal proximal tubules. Fatty acids are bound with L-FABP and transported to the mitochondria or peroxisomes, where fatty acids are beta-oxidized, and this may play a role in fatty acid homeostasis. Moreover, L-FABP has high affinity and capacity to bind long-chain fatty acid oxidation products, and may be an effective endogenous antioxidant. Renal L-FABP is rarely expressed in the kidneys of rodents. In order to evaluate the pathological dynamics of renal L-FABP in kidney disease, human L-FABP chromosomal transgenic mice were generated. Various stress, such as massive proteinuria, hyperglycemia, hypertension, and toxins overloaded in the proximal tubules were revealed to up-regulate the gene expression of renal L-FABP and increase the excretion of L-FABP derived from the proximal tubules into urine. In clinical studies of chronic kidney disease (CKD), urinary L-FABP accurately reflected the degree of tubulointerstitial damage and correlated with the rate of CKD progression. Furthermore, a multicenter trial has shown that urinary L-FABP is more sensitive than urinary protein in predicting the progression of CKD. With respect to diabetic nephropathy and acute kidney disease (AKI), urinary L-FABP is an early diagnostic of kidney disease or a predictive marker for renal prognosis. After many clinical studies, urinary L-FABP was approved as a new tubular biomarker promulgated by the Ministry of Health, Labour and Welfare in Japan.
肝型脂肪酸结合蛋白(L-FABP)是一种14kDa的蛋白质,存在于人类肾近端小管的细胞质中。脂肪酸与L-FABP结合并被转运至线粒体或过氧化物酶体,在那里脂肪酸进行β氧化,这可能在脂肪酸稳态中发挥作用。此外,L-FABP对长链脂肪酸氧化产物具有高亲和力和结合能力,可能是一种有效的内源性抗氧化剂。肾L-FABP在啮齿动物肾脏中很少表达。为了评估肾L-FABP在肾脏疾病中的病理动态变化,制备了人L-FABP染色体转基因小鼠。研究发现,各种应激,如大量蛋白尿、高血糖、高血压以及近端小管中毒素超载,均可上调肾L-FABP的基因表达,并增加源自近端小管的L-FABP向尿液中的排泄。在慢性肾脏病(CKD)的临床研究中,尿L-FABP准确反映了肾小管间质损伤程度,并与CKD进展速率相关。此外,一项多中心试验表明,尿L-FABP在预测CKD进展方面比尿蛋白更敏感。对于糖尿病肾病和急性肾损伤(AKI),尿L-FABP是肾脏疾病的早期诊断指标或肾脏预后的预测标志物。经过多项临床研究,尿L-FABP被日本厚生劳动省批准为一种新的肾小管生物标志物。