Glycosaminoglycans urinary excretion as a marker of the early stages of diabetic nephropathy and the disease progression

Abstract

In conclusion, it can be stated that all patients with DM compared to the control group show an increase in GAG excretion independent of diabetes duration. Urinary GAG excretion positively correlates with the duration of diabetic nephropathy. The assessment of GAG excretion values may be useful for determining the early stages of diabetic nephropathy and the progression of the disease.

Urinary Markers of Glomerular Injury in Diabetic Nephropathy

“…Most of the studies found that GAGs excretion increases as albumin excretion increases [96, 99, 100, 108, 109], two studies did not find a correlation [95, 106], and one study found a decrease in GAGs excretion as UAE increases [101]. Torffvit et al [101] found a decrease in sulphated GAGs excretion (but not of GAGs/creatinine ratio) between normoalbuminuric and albuminuric type 1 diabetic patients.…”

“…Diabetic patients with manifest nephropathy have increased urinary GAGs compared to patients with incipient nephropathy [94, 99, 108], and their sensitivity in patients with manifest nephropathy has been reported to be 100%, compared to 77% of albuminuria [99]. …”

“…In diabetic patients, there is a correlation between urinary GAGs excretion and blood pressure [99, 101, 106, 108], but conflicting results have been published regarding their correlation with duration of diabetes [94, 96, 99, 106, 108, 110] and glycemic control [94, 96, 99, 101, 102, 106, 108, 109]. …”

Urinary biomarkers for early diabetic nephropathy: beyond albuminuria

“…Studies show that diabetic patients excrete significantly more GAGs than the control group [32]. Moreover, increased urinary GAGs have been detected in patients with microalbuminuria or macroalbuminuria, and positively correlated with the duration of DN [33]. …”

Diabetic nephropathy: is it always there? Assumptions, weaknesses and pitfalls in the diagnosis

“…Diabetic patients excrete in urine significantly more glycosaminoglycans (GAGs), part of the endothelial glycocalyx, than controls 80 and such an increase has been reported in patients with all stages of albuminuria, while urinary GACs positively correlated with disease progression. 81 Moreover, several other proteins have been reported to increase in the urine of diabetic patients. Extracellular structural matrix proteins (collagen type IV, fibronectin, metalloproteinases), transforming growth factor (TGF)beta the potent inducer of extracellular matrix proteins, markers of tubular damage like the apical membrane receptors megalin and cubilin, the transmembrane protein of the apical membrane of PTCs-kidney injury molecule 1 (KIM-1), but also neutrophil gelatinase-associated lipocalin (NGAL) that is produced in the distal nephron are examples of such proteins.…”