Urinary biomarkers involved in type 2 diabetes: a review

Abstract

Diabetes mellitus is one of the most challenging health concerns of the 21st century. With at least 30% of the diabetic population remaining undiagnosed, effective and early diagnosis is of critical concern. Development of a diagnostic test, more convenient and reliable than those currently used, would therefore be highly beneficial. Urine as a diagnostic medium allows for non-invasive detection of biomarkers, including some associated with type 2 diabetes and its complications. This review provides a synopsis of those urinary biomarkers that potentially may provide a basis for the development of improved diagnostic tests. Three main pathways for the sourcing of potential makers are identified: kidney damage, oxidative stress and low-grade inflammation including atherosclerosis/vascular damage. This review briefly presents each pathway and some of the most relevant urinary biomarkers that may be used to monitor the development or progression of diabetes and its complications. In particular, biomarkers of renal dysfunction such as transferrin, type IV collagen and N-acetyl-beta-D-glucosaminidase might prove to be more sensitive than urinary albumin, the current gold standard, in the detection of incipient nephropathy and risk assessment of cardiovascular disease. Inflammatory markers including orosomucoid, tumour necrosis factor-alpha, transforming growth factor-beta, vascular endothelial growth factor and monocyte chemoattractant protein-1, as well as oxidative stress markers such as 8-hydroxy-2'deoxyguanosine may also be useful biomarkers for diagnosis or monitoring of diabetic complications, particularly kidney disease. However, the sensitivity of these markers compared with albumin requires further investigation.

The role of novel biomarkers in predicting diabetic nephropathy: a review

“…For example, not all diabetics with microalbuminuria will end up with ESKD, 8,14 and 30% of them may actually have normoalbuminuria, 15 while several biomarkers of glomerular or tubular dysfunction can precede microalbuminuria, suggesting that microalbuminuria is present once significant renal injury has already occurred. 16 Nevertheless, its predictive accuracy can be enhanced by other parameters such as a painstaking family history, consideration of absolute versus categorical urine albumin excretion (UAE) values, more frequent UAE estimates, ambulatory blood pressure monitoring, precise GFR measurements, diabetic retinopathy assessments, and plasma lipid profile. 13 Interestingly, there is now a paradigm shift to novel biomarkers which would help to predict DN risk early enough, and possibly prevent the occurrence of ESKD.…”

Diagnosis and Prediction of CKD Progression by Assessment of Urinary Peptides

“…This has initiated research to identify noninvasive urinary protein biomarkers of CKD that enable early detection and accurate prognosis. [10][11][12] Urinary proteome analysis by capillary electrophoresis (CE) coupled to mass spectrometry (MS) has shown high reproducibility allowing the comparison of the protein and peptide content of thousands of samples. 13 Hence, CE-MS has been used to analyze urine samples from patients with various renal and nonrenal diseases.…”

Elevated levels of renal and circulating Nop-7-associated 2 (NSA2) in rat and mouse models of diabetes, in mesangial cells in vitro and in patients with diabetic nephropathy

“…Emerging candidate biomarkers of renal dysfunction include markers of glomerular damage, oxidative stress and inflammation. To date, UAE remains the universally accepted biomarker in clinical practice [31]. One promising new biomarker is cystatin C, a cysteine protease inhibitor that is increased in serum and urine of patients with DN [32][33][34].…”