Urinary biomarkers for early diabetic nephropathy in type 2 diabetic patients

Abstract

Diabetic nephropathy (DN) is a serious complication of diabetes associated with increased risk of mortality, and cardiovascular and renal outcomes. Diagnostic markers to detect DN at early stage are important as early intervention can slow loss of kidney function and improve patient outcomes. Urinary biomarkers may be elevated in diabetic patients even before the appearance of microalbuminuria, and can be used as useful marker for detecting nephropathy in patients with normoalbuminuria (early DN). We reviewed some new and important urinary biomarkers, such as: Neutrophil gelatinase associated lipocalin (NGAL), N-acetyl-beta-glucosaminidase (NAG), Cystatin C, alpha 1-microglobulin, immunoglobulin G or M, type IV collagen, nephrin, angiotensinogen and liver-type fatty acid-binding protein (L-FABP) associated with early DN in type 2 diabetic patients. Our search identified a total of 42 studies that have been published to date. Urinary levels of these biomarkers were elevated in type 2 diabetic patients compared with non-diabetic controls, including in patients who had no signs indicating nephropathy (without microalbuminuria), and showed positive correlation with albuminuria. Despite the promise of these new urinary biomarkers, further large, multicenter prospective studies are still needed to confirm their clinical utility as a screening tool for early type 2 DN in every day practice.

Performance of urinary neutrophil gelatinase-associated lipocalin, clusterin, and cystatin C in predicting diabetic kidney disease and diabetic microalbuminuria: a consecutive cohort study

“…Urinary CysC has also been suggested as an indicator of tubular dysfunction for the early diagnosis of DKD [21, 38, 39]. Previous results and conclusions include an early rise of uCysC in T2DM patients [24], an association with a declining GFR [21], and a rise in urine ACR [24], which are consistent with an alteration in the degree of albuminuria [21].…”

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

“…91 Similarly, elevated urinary NGAL is present in normoalbuminuric diabetic patients, as well as used to assess tubular lesions in the disease, 92 and has been shown to precede microalbuminuria in T1DM. 93,94 In addition, high values of this biomarker were noted in T2DM patients with normoalbuminuria which rose progressively in patients with microalbuminuria and macroalbuminuria.…”

Urine AQP5 is a potential novel biomarker of diabetic nephropathy

“…AQP5 may, thus be added to the list of tubular markers such as kidney injury molecule-1, α1-microglobulin, and retinol binding protein (RBP). These complement the growing list of urine-accumulated tubular epithelial- and glomerular-derived proteins that may have prognostic significance in the context of diabetic renal disease including lipocalin 2, N-acetyl-beta-glucosaminadase, cystatin C, type IV collagen, nephrin, angiotensinogen, L-FABP, the serine proteinase inhibitor PAI-1 and miR-192 (Fiseha, 2015; Jia et al, 2016; Torii et al, 2004). Inclusion of these in patient assessments is likely to provide a more complete evaluation of disease status compared to the more traditional use of a marker of glomerular dysfunction such as albumin (Matheson, Willcox, Flanagan, & Walsh, 2010).…”