DESCRIPTION: Diabetic nephropathy (DN) is one of the major microvascular complications of diabetes and the most common cause of end-stage renal disease (ESRD)1,2. Previously, diabetic kidney disease (DKD) was thought to be a unidirectional process that starts with microalbuminuria and leads to end-stage renal failure.
Dipeptidyl peptidase-IV (DPP-IV, CD26 or P32/98) is a potential molecular biomarker in diabetic kidney disease
DESCRIPTION: Diabetic nephropathy (DN) is one of the major microvascular complications of diabetes and the most common cause of end-stage renal disease (ESRD)1,2. Previously, diabetic kidney disease (DKD) was thought to be a unidirectional process that starts with microalbuminuria and leads to end-stage renal failure. However, recent studies have shown that a large proportion of patients diagnosed with DKD may reverse back to normoalbuminuria3,4. Therefore, the development of more sensitive and reliable markers for early detection of DKD are needed.
Urine is one of the most useful resources for such a study, as its collection is simple and non-invasive. In addition to soluble plasma proteins, urinary microvesicles, such as exosomes and microparticles, have recently been the targets of urine proteomic analysis.
Previous reports have indicated that a high level of plasma dipeptidyl peptidase-IV (DPP IV), also known as CD26 or p32/98, is positively correlated with diabetes mellitus (DM). DPP IV is a membrane-associated peptidase and is widely expressed in all tissues. In the kidney, where the enzyme is exceptionally concentrated, it is located primarily in the cortex and found in the brush border and microvillus fractions.
On the basis of these findings, we hypothesized that DPP IV might be a protein component of urinary microvesicles, and its activity might represent the concentration of microvesicles, secreted by tubular epithelial cells, in the urine. DPP IV is an intrinsic membrane glycoprotein, localized on glomerular visceral epithelial cells, endothelial cells, and the proximal tubule brush border. DPP IV has been shown to participate in T-cell biology as a co-stimulatory molecule able to regulate signaling transduction pathways.5-7. In addition to its role in T-cell biology, DPP IV also plays an important role in the pathogenesis of kidney diseases such as IgA nephropathy8.
These results suggested that the microvesicle-bound DPP IV in urine may be secreted from tubular epithelial cells and be related to early tubular impairment, and thus it may be an early marker of renal damage before onset of albuminuria. However, the mechanism of increased urinary DPP IV excretion in patients with DKD remains unclear. These findings indicate that urinary microvesicle-bound DPP IV is a specific marker for DKD. The measurement of urinary microvesicle-bound DPP IV might be a useful method for DKD screening and diagnosis in patients with T2DM. Whether it can be used as a marker for other kind of kidney diseases needs to be further investigated 9.
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- Reutens AT, Prentice L and Atkins R. The epidemiology of diabetic kidney disease. In: Ekoe J. (ed) The epidemiology of diabetes mellitus, 2nd ed. Chichester: John Wiley & Sons Ltd, 2008, pp. 499-518.
- National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. International comparisons. in: 2007 annual data report: atlas of chronic kidney disease and end-stage renal disease in the United States.
- Bethesda: National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2007, pp. 239-254.
- Wiseman MJ and Viberti G. Genesis and evolution of proteinuria in diabetes mellitus. Ric Clin Lab 1985; 15: 9-16.
- Krempf M, du Rostu H, Murat A, et al. Radioimmunoassay of urinary albumin: early indicator of diabetic nephropathy? Rev Med Interne 1985; 6: 510-514.
- Sato K, Aytac U, Yamochi T, et al. CD26/dipeptidyl peptidase IV enhances expression of topoisomerase II alpha and sensitivity to apoptosis induced by topoisomerase II inhibitors.Br J Cancer 2003; 89: 1366-1374.
- Sato T, Yamochi T, Aytac U, et al. CD26 regulates p38mitogen-activated protein kinase-dependent phosphorylation of integrin beta1, adhesion to extracellular matrix, and tumorigenicity of T-anaplastic large cell lymphoma Karpas 299. Cancer Res 2005; 65: 6950-6956.
- Yamochi T, Aytac U, Sato T, et al. Regulation of p38 phosphorylation and topoisomerase II alpha expression in the B-cell lymphoma line Jiyoye by CD26/dipeptidyl peptidase IV is associated with enhanced in vitro and in vivo sensitivity to doxorubicin. Cancer Res 2005; 65: 1973-1983.
- Mitic B, Lazarevic G, Vlahovic P, et al. Diagnostic value of the aminopeptidase N, N-acetyl-b-D-glucosaminidase and Dipeptidyl-peptidase IV in evaluating tubular dysfunction in patients with glomerulopathies. Ren Fail 2008; 30: 896-903.
- Ai-li Sun et al. Dipeptidyl peptidase-IV is a potential molecular biomarker in diabetic kidney disease. Diabetes and Vascular Disease Research 2012. 9: 9(4) 301-308.