Possible Biomarkers for Diabetic Kidney Disease

The prevalence of diabetes is increasing worldwide and is the highest in the Western Pacific region, which includes Japan. There is an urgent need for the development of new diabetic kidney disease (DKD) biomarkers, in addition to those currently available from early diagnosis and specific detection to prognostic prediction and assessment of treatment response. Multiple biomarkers for DKD have been described and validated. There are some biomarkers which are available in clinical setting and novel. Traditional biomarkers include albumin, which has been well used for a long time and important for diagnosis of early DKD, neutrophil gelatinase-associated lipocalin, α-1-microglobulin, kidney injury molecule-1, L-type fatty acid binding protein, angiotensinogen, cystatin C, N-acetyl-glucosaminidase, and so on. A variety of factors have been shown to contribute to the progression of DKD. As chronic inflammation is one of these factors, all inflammatory cytokines can be used as biomarkers of DKD. Serum interleukin (IL)-6, IL-8, IL-18, monocyte chemoattractant protein, and interferon-inducible protein are reportedly higher in the urine of patients with early kidney damage. Serum and urinary tumor necrosis factor-α is also reportedly elevated from the early stage of DKD. In addition, some growth factor, such as transforming growth factor-β and connective tissue growth factor, and adhesion molecules are associated with end-stage kidney failure or mortality. Other factors include fetuin-A, which is a vascular calcification inhibitor that is secreted by the liver CD40 ligands, which are expressed in B cells, antigen-presenting cells, and vascular endothelial cells, and human α1 acid glycoprotein (orosomucoid). The estimated number of metabolites in the human body ranges between 3000 and 8000. Urinary metabolomic analysis using gas chromatography and mass spectrometry in combination has allowed researchers to identify profiles showing that decreases in the amounts of organic acids excreted in the urine, due to abnormalities in OKT1, OKT3, and other organic anion transporters, are more likely to occur in patients with DKD rather than in those without DKD. We obtained urinary metabolites with a positive or inverse correlation with albuminuria and kidney function and are currently conducting assessments of unidentified and identified peaks, using these metabolites as biomarkers. In addition, it was reported that urinary miRNA profiles showed promise for use in the early diagnosis and prognostic prediction of nephropathy in type 1 diabetes patients. Novel biomarkers have been identified in blood (e.g., aspartic acid, SMDA, azelaic acid, galactaric acid, tryptophan metabolites) and urine (e.g., L-FABP, C-megalin, and WT-1) as an early diagnosis marker and in blood (e.g., autoantibodies to erythropoietin receptor, tryptophan metabolites) and urine (e.g., L-FABP, A-megalin, and WT-1) as a prognostic prediction marker.