Expression of synaptopodin and GLEPP1 as markers of steroid responsiveness in primary focal segmental glomerulosclerosis

Life Sci. 2006 Jul 17;79(8):757-63. doi: 10.1016/j.lfs.2006.02.031. Epub 2006 Mar 27.


The crucial involvement of podocyte failure in the development of hereditary focal segmental glomerulosclerosis (FSGS) indicates that specific podocyte proteins are closely related to podocyte function and biology. We hypothesized that podocyte failure, reflected by alteration of these proteins, leads not only to FSGS but also to resistance to steroid therapy. We investigated the association between expression of synaptopodin and glomerular epithelial protein 1 (GLEPP1) and response to corticosteroid therapy in primary FSGS. The subjects of this retrospective study were 17 adult patients with primary FSGS with nephrotic syndrome (NS) seen at Fukuoka Red Cross Hospital between 1979 and 2001. They were divided into two groups according to the response to steroid therapy at 6months: responders (n=10) and non-responders (persistence of nephrotic-range proteinuria, n=7). Expression levels of synaptopodin and GLEPP1 were examined immunohistochemically using image analysis software. Low expression levels of both proteins were associated with poor steroid responsiveness in FSGS. The average gray values for synaptopodin and GLEPP1 expression in responders vs. non-responders were 9.0+/-0.7 (mean+/-S.E.M.) vs. 6.3+/-0.9 (P=0.04) and 9.6+/-1.2 vs. 6.0+/-1.0 (P=0.04), respectively. The percentages of glomerular area staining for synaptopodin and GLEPP1 in responders vs. non-responders were 15.4+/-2.7% vs. 8.1+/-1.2% (P=0.045) and 11.9+/-1.6% vs. 6.0+/-1.3% (P=0.02), respectively. Synaptopodin expression correlated with the severity of proteinuria and with GLEPP1 expression. Reduced expression of both synaptopodin and GLEPP1 is associated with poor response to steroid therapy in primary FSGS.

MeSH terms

  • Adult
  • Glomerulosclerosis, Focal Segmental / diagnosis
  • Glomerulosclerosis, Focal Segmental / drug therapy*
  • Glomerulosclerosis, Focal Segmental / metabolism
  • Humans
  • Immunohistochemistry
  • Kidney Glomerulus / chemistry*
  • Male
  • Membrane Proteins / analysis*
  • Microfilament Proteins / analysis*
  • Podocytes / chemistry
  • Podocytes / cytology
  • Prednisolone / administration & dosage
  • Prednisolone / therapeutic use*
  • Protein Tyrosine Phosphatases / analysis*
  • Proteinuria / drug therapy
  • Proteinuria / genetics
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3
  • Retrospective Studies


  • Membrane Proteins
  • Microfilament Proteins
  • SYNPO protein, human
  • Prednisolone
  • PTPRO protein, human
  • Protein Tyrosine Phosphatases
  • Receptor-Like Protein Tyrosine Phosphatases, Class 3