e., albuminuria); stage III: ACR ≥ 300 mg/g creatinine and/or persistent proteinuria with serum concentration of creatinine <2 mg/dl; stage IV: serum concentration of

creatinine ≥2 mg/dl with proteinuria; and stage V: being treated with dialysis. The Japan Diabetes Clinical Data Management Study Group (JDDM) reported that the prevalence of albuminuria (stage II) in Japanese type 2 diabetic patients was 32%, which is very similar to the 39% observed in the DEMAND study [12]. These results suggest that albuminuria is common, and that 76% of patients with diabetic nephropathy are categorized as stage II, as evidenced by the presence of albuminuria. Further, 58% of the patients enrolled were at stage I, 7% were at stage III, 2.6% were at stage IV, and 0.4% were at stage V [11]. A very recent study from the Japan Diabetes Complications Study (JDCS) revealed that the annual transition SCH772984 in vivo rate to proteinuria (ACR ≥ 300 mg/g creatinine) was 0.67%, and that this was substantially higher for the low-albuminuric group (defined as a urinary

ACR of 30–150 mg/g creatinine) than for the normoalbuminuric group (defined as a Epacadostat manufacturer urinary ACR of <30 mg/g creatinine) [13]. In this sense, UKPDS 64 reported that the progression to albuminuria occurred at 2.0% per year, and from albuminuria to macroalbuminuria at 2.8% per year [14]. However, about 40% of the diabetic patients had no urinary albumin excretion measurements, regardless of the recommendation for GDC-0994 mouse the JDDM cohort [11]. Therefore, the measurement of urinary albumin excretion is required for the early detection of diabetic nephropathy in Japan. Biomarkers for diabetic nephropathy and disease progression Further studies to detect diabetic nephropathy more specifically at the early stage in addition to urinary albumin excretion are needed. In this sense, biomarker studies to identify the presence and predict the progression of diabetic nephropathy MycoClean Mycoplasma Removal Kit have been performed worldwide [15]. Recently, Kamijo-Ikemori et al. [16]

reported that urinary levels of liver-type fatty acid-binding protein (L-FABP) accurately reflected the severity of diabetic nephropathy in type 2 diabetes. Importantly, urinary L-FABP levels were high in patients with normoalbuminuria, suggesting its usefulness for detecting early nephropathy in these patients. Further, an increase in urinary Smad1—a key transcriptional factor for mesangial matrix expansion in diabetic nephropathy—at the early stage was correlated with subsequent development of glomerulosclerosis in experimental rodent models [17]. Regarding renal function, serum cystatin C was reported to be a good marker for nephropathy [18]. Notably, cases of early renal dysfunction, defined by a loss of cystatin C GFR exceeding −3.3%/year, occurred in 9% of the normoalbuminuria group and 31% of the albuminuria group [19].