title: Urinary heparanase activity in patients with Type 1 and Type 2 diabetes.
abstract: 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.
authors.affiliation: Nephrology Research Laboratory, Department of Nephrology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Angelique L W M M
authors.initials: AL
authors.lastname: Rops
authors.forename: Mabel J
authors.initials: MJ
authors.lastname: van den Hoven
authors.forename: Bart A
authors.initials: BA
authors.lastname: Veldman
authors.forename: Simone
authors.initials: S
authors.lastname: Salemink
authors.forename: Gerald
authors.initials: G
authors.lastname: Vervoort
authors.forename: Lammy D
authors.initials: LD
authors.lastname: Elving
authors.forename: Jan
authors.initials: J
authors.lastname: Aten
authors.forename: Jack F
authors.initials: JF
authors.lastname: Wetzels
authors.forename: Johan
authors.initials: J
authors.lastname: van der Vlag
authors.forename: Jo H M
authors.initials: JH
authors.lastname: Berden
mesh_terms: D000328:Adult; D000368:Aged; D000419:Albuminuria / Q000175:diagnosis; D015153:Blotting, Western; D016022:Case-Control Studies; D048909:Diabetes Complications / Q000201:enzymology / Q000209:etiology / Q000652:urine; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology* / Q000652:urine*; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology* / Q000652:urine*; D005260:Female; D005500:Follow-Up Studies; D050533:Glomerular Basement Membrane / Q000473:pathology*; D005966:Glucuronidase / Q000235:genetics / Q000652:urine*; D006497:Heparan Sulfate / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012084:Renin-Angiotensin System; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D006497:Heparan Sulfate; D012333:RNA, Messenger; D000099175:Heparanase