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 β2-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.
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 diabeticpatients (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 diabeticpatients treated with inhibitors of the renin-angiotensin-aldosterone system (RAAS), when compared to diabeticpatients treated with other anti-hypertensives. Additionally, urinary heparanase activity was associated with age in T1D and MGP. In MGP, heparanase activity and β2-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 diabeticpatients with proteinuria. However, whether increased heparanase activity is a cause or consequence of proteinuria requires additional research.
Authors: Sunil Rangarajan; Jillian R Richter; Robert P Richter; Shyam K Bandari; Kaushlendra Tripathi; Israel Vlodavsky; Ralph D Sanderson Journal: J Histochem Cytochem Date: 2020-07-06 Impact factor: 2.479
Authors: Melissa I Lygizos; Yimu Yang; Christopher J Altmann; Kayo Okamura; Ana Andres Hernando; Mario J Perez; Lynelle P Smith; Daniel E Koyanagi; Aneta Gandjeva; Rhea Bhargava; Rubin M Tuder; Sarah Faubel; Eric P Schmidt Journal: Physiol Rep Date: 2013-11-11
Authors: Charmaine J Simeonovic; Andrew F Ziolkowski; Zuopeng Wu; Fui Jiun Choong; Craig Freeman; Christopher R Parish Journal: Front Immunol Date: 2013-12-26 Impact factor: 7.561
Authors: Conrado L R Gomes; Cristina L Leão; Carolina Venturotti; André L Barreira; Gabriela Guimarães; Roberto J C Fonseca; Rodrigo S Fortunato; Paulo A S Mourão; Alvimar G Delgado; Christina M Takiya; Maurilo Leite Journal: PLoS One Date: 2014-09-05 Impact factor: 3.240