With

regard to DN, a streptozotocin (STZ)-induced diabetic model, which has type 1 diabetes, was used and tubulointerstitial damage was provoked. Our findings revealed that renal human L-FABP gene expression was up-regulated (around 9-fold increase) and that urinary excretion of human L-FABP increased (around 9-fold increase) in the STZ-induced diabetic Tg mice compared with control mice at 8 weeks after STZ injection. From the observation Venetoclax research buy of lipid accumulation in human proximal tubules in DN, it could be suggested that lipid or peroxidation product generated in the proximal tubules of DN might promote the up-regulation of renal L-FABP expression. Our Tg mice were generated by microinjections of the genomic DNA of human L-FABP including its promoter

region; therefore, it is possible for the transcription of the human L-FABP gene in the Tg mice to be regulated in the same mode as in humans. The dynamics of human L-FABP in the experimental diabetic model might mimic those under pathological conditions in humans. In recent clinical studies of patients with type 2 diabetes, MK-1775 chemical structure we showed that urinary L-FABP concentrations increased with the progression of DN and reflected DN severity. Urinary L-FABP levels were significantly higher in patients with normoalbuminuria than in control subjects. This result indicated that urinary L-FABP accurately reflected severity of diabetic kidney disease and may be a suitable biomarker for

early detection of diabetic kidney disease. In the prospective study, urinary L-FABP was an independent predictor of progression of DN, which was defined as advancement to the next higher stage in patients with all stages of DN without the requirement of dialysis or kidney transplantation; analysis of a subgroup with an estimated GFR (eGFR) >60 ml/min per 1.73 m2 showed results consistent with the former result. A high urinary L-FABP value at study entry was a higher risk factor for progression of DN than the presence of albuminuria at entry. Although without significance (P = 0.45), the AUC for predicting the progression of DN by urinary L-FABP (AUC = 0.762) was higher than that by urinary albumin (AUC = 0.675) in the subgroup with an eGFR >60 ml/min Ribose-5-phosphate isomerase per 1.73 m2. Urinary L-FABP may be a useful biomarker for predicting progression of DN. Moreover, therapeutic interventions with renoprotective effects were reported to reduce urinary L-FABP concentrations by another studies. 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 presentation summarizes the clinical significance of urinary L-FABP in type 2 DN.