Urinary heparanase activity in patients with Type 1 and Type 2 diabetes.
SourceNephrology, Dialysis, Transplantation, 27, 7, (2012), pp. 2853-2861
1 juli 2012
Article / Letter to editor
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Nephrology, Dialysis, Transplantation
SubjectIGMD 5: Health aging / healthy living; NCMLS 1: Infection and autoimmunity N4i 4: Auto-immunity, transplantation and immunotherapy; NCMLS 3: Tissue engineering and pathology N4i 4: Auto-immunity, transplantation and immunotherapy; IGMD 9: Renal disorder
Background A reduced heparan sulphate (HS) expression in the glomerular basement membrane of patients with overt diabetic nephropathy is associated with an increased glomerular heparanase expression. We investigated the possible association of urinary heparanase activity with the development of proteinuria in patients with Type 1 diabetes (T1D), Type 2 diabetes (T2D), or membranous glomerulopathy (MGP) as non-diabetic disease controls. Methods Heparanase activity, albumin, HS and creatinine were measured in the urine of patients with T1D (n = 58) or T2D (n = 31), in patients with MGP (n = 52) and in healthy controls (n = 10). Heparanase messenger RNA (mRNA) expression in leukocytes was determined in a subgroup of patients with T1D (n = 19). Results Urinary heparanase activity was increased in patients with T1D and T2D, which was more prominent in patients with macroalbuminuria, whereas no activity could be detected in healthy controls. Albuminuria levels were associated with increased urinary heparanase activity in diabetic patients (r = 0.20; P < 0.05) but not in patients with MGP (r = 0.11; P = 0.43). A lower urinary heparanase activity was observed in diabetic patients treated with inhibitors of the renin-angiotensin-aldosterone system (RAAS), when compared to diabetic patients treated with other anti-hypertensives. Additionally, urinary heparanase activity was associated with age in T1D and MGP. In MGP, heparanase activity and beta2-microglobulin excretion correlated. In patients with T1D, no differences in heparanase mRNA expression in leukocytes could be observed. Conclusions Urinary heparanase activity is increased in diabetic patients with proteinuria. However, whether increased heparanase activity is a cause or consequence of proteinuria requires additional research.
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