title: Heparanase activity is dysregulated in children with steroid-sensitive nephrotic syndrome.
abstract: BACKGROUND
  Immune cells express heparanase, an endoglycosidase, able to degrade heparan sulfate glycosaminoglycan (HSGAG) in the glomerular capillary wall (GCW) and potentially induce proteinuria. The aim of this study was to determine whether dysregulated heparanase expression is associated with the heavy proteinuria of childhood steroid-sensitive nephrotic syndrome (SSNS).
  
  
  METHODS
  Plasma and urinary heparanase activity and peripheral blood mononuclear cell (PBMC) mRNA heparanase levels [real-time polymerase chain reaction (PCR)] were measured in children with SSNS in relapse and remission. Plasma and urinary heparanase activity was determined in adult patients with nephrotic syndrome and in age- and gender-matched controls.
  
  
  RESULTS
  Plasma heparanase activity was reduced in SSNS with relapse (811.2 units) compared to remission (1147.96 units) (P= 0.003) and control subjects (1390.51 units) (P < 0.001). In adult nephrotic syndrome, plasma heparanase activity was significantly lower in patients compared to controls. However, there was no difference between remission and relapse states. In children, urinary heparanase activity/urinary creatinine ratio was highest in SSNS relapse (14.26 units/mg) compared with remission (7.43 units/mg) (P= 0.016) and controls (2.29) (P < 0.001). However, PBMC heparanase mRNA expression was not different between these three groups. In adult nephrotic syndrome, urinary heparanase activity/urinary creatinine levels were lower in both remission and relapse compared to controls and there was no difference between remission and relapse states.
  
  
  CONCLUSIONS
  In childhood SSNS, there is a qualitative and quantitative difference in urinary heparanase activity expression that is not paralleled in adult nephrotic syndrome. These data suggest that dysregulated heparanase expression may play a significant role in the pathogenesis of SSNS, possibly through an abnormality in post-translational control of latent heparanase activation.
authors.affiliation: Department of Paediatric Nephrology, Royal Manchester Children's Hospital, Manchester, United Kingdom.
authors.forename: Richard C L
authors.initials: RC
authors.lastname: Holt
authors.forename: Nicholas J A
authors.initials: NJ
authors.lastname: Webb
authors.forename: Shirley
authors.initials: S
authors.lastname: Ralph
authors.forename: John
authors.initials: J
authors.lastname: Davies
authors.forename: Colin D
authors.initials: CD
authors.lastname: Short
authors.forename: Paul E C
authors.initials: PE
authors.lastname: Brenchley
mesh_terms: D000328:Adult; D000367:Age Factors; D016022:Case-Control Studies; D002648:Child; D004789:Enzyme Activation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006497:Heparan Sulfate / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D009404:Nephrotic Syndrome / Q000188:drug therapy* / Q000201:enzymology* / Q000235:genetics; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012008:Recurrence; D013256:Steroids / Q000627:therapeutic use*; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D006497:Heparan Sulfate; D012333:RNA, Messenger; D013256:Steroids; D000099175:Heparanase