Urinary liver type fatty acid binding protein in diabetic nephropathy

Abstract

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.

Increment of HFABP Level in Coronary Artery In-Stent Restenosis Segments in Diabetic and Nondiabetic Minipigs: HFABP Overexpression Promotes Multiple Pathway-Related Inflammation, Growth and Migration in Human Vascular Smooth Muscle Cells

“…Previous studies have demonstrated a significant association of AFABP with diabetes and atherosclerosis, a remarkable increase of HFABP in serum during pulmonary embolism, acute coronary syndrome and heart failure, the close relation of urinary FABP to diabetic nephropathy, the contribution of epidermal FABP to HER2-induced mammary tumors and diabetic vascular complications and the impact of brain-type FABP on liver injury [7,8,9,10,11,12,13,14,15,32,33,34,35]. Our findings, including our previous proteomic experiment results, show that AFABP and HFABP levels are significantly increased in ISR tissue versus in non-ISR tissue, and that the overexpression of AFABP and HFABP could promote growth and migration in VSMCs, indicating the substantial role of these 2 FABP members in ISR formation [6,7].…”

Biological characterization of liver fatty acid binding gene from miniature pig liver cDNA library

“…Regardless of whether the mice are back-crossed to a C57Bl/6NCr background as described here or a C57Bl/6J background as described by others, L-FABP (-/-) mice fed the control chow ad libitum exhibited decreased hepatic long-chain fatty acid uptake, cytosolic long-chain fatty acid binding capacity, long-chain fatty acid b-oxidation, and peroxisomal branched-chain long-chain fatty acid oxidation (Martin et al, 2003;Atshaves et al, 2004;Kamijo-Ikemori and Sugaya, 2010;McIntosh et al, 2013). The experiments carried out in this study indicate that the L-FABP is involved in gene regulation via PPARα and PPARg in hepatocytes.…”

Urinary Level of Liver-Type Fatty Acid Binding Protein Reflects the Degree of Tubulointerstitial Damage in Polycystic Kidney Disease

“…The urinary level of liver-type fatty acid binding protein (L-FABP) was identified as an excellent tubular marker of chronic kidney disease (CKD) and acute kidney injury (AKI) in a clinical setting, and was subsequently approved as a tubular biomarker by the Ministry of Health, Labor and Welfare in Japan [10][11][12]. Furthermore, higher urinary L-FABP levels were reported in the patients with ADPKD, compared to healthy subjects [13]; however, the relationship between the urinary L-FABP levels and the renal pathology associated with PKD, or between the change in urinary L-FABP levels and PKD progression, has not previously been investigated.…”