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Abstract: PO0733

Proteome Analysis of Glomerular Formalin-Fixed Paraffin Embedded Kidney Samples Distinguishes Diabetic Nephropathy from Controls

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Nagelkerken, Sophie I., Leids Universitair Medisch Centrum Afdeling Pathologie, Leiden, Zuid-Holland, Netherlands
  • Janssen, George, Leids Universitair Medisch Centrum Center for Proteomics and Metabolomics, Leiden, Netherlands
  • Veraar, Kimberley, Leids Universitair Medisch Centrum Afdeling Pathologie, Leiden, Zuid-Holland, Netherlands
  • Van veelen, Peter, Leids Universitair Medisch Centrum Center for Proteomics and Metabolomics, Leiden, Netherlands
  • Baelde, Hans J., Leids Universitair Medisch Centrum Afdeling Pathologie, Leiden, Zuid-Holland, Netherlands
  • Lardenoije, Roy, University Medical Center Göttingen Department of Psychiatry and Psychotherapy, Göttingen, Germany
  • Rotmans, Joris I., Leids Universitair Medisch Centrum Niercentrum, Leiden, Zuid-Holland, Netherlands
  • Bruijn, Jan A., Leids Universitair Medisch Centrum Afdeling Pathologie, Leiden, Zuid-Holland, Netherlands
  • Bajema, Ingeborg M., Leids Universitair Medisch Centrum Afdeling Pathologie, Leiden, Zuid-Holland, Netherlands
Background

Liquid chromatography tandem-mass spectrometry (LC-MS/MS) is a sensitive technique for in depth proteome analysis but its usage as a diagnostic tool for kidney diseases is still in development. We investigated the potential use of LC-MS/MS in diagnosing diabetic nephropathy (DN) in renal biopsies.

Methods

Biopsies from 10 DN patients without renal comorbidity were compared to 10 pretransplantation biopsies. Glomerular cross-sections were collected using laser capture microdissection and tryptic peptides were analysed using LC-MS/MS. Resulting spectra were used for protein identification and further analysis.

Results

Based on all identified proteins, DN patients and controls clustered separately (Figure 1). Moreover, we identified 47 significant differentially expressed proteins after adjusting for multiple testing. In DN proteins with increased expression included collagens IV, VI and XVIII, fibronectin, vitronectin, fibulin, complement component C3, C4 and C9, complement factor H, clusterin, fibrinogen and apolipoprotein E. Proteins with decreased expression in DN included nephrin, chloride intracellular channel protein 5, Rab GDP dissociation inhibitor alpha and complement receptor 1.

Conclusion

Proteins identified by LC-MS/MS from glomerular cross-sections successfully distinguished kidney biopsies with DN from normal kidneys. Moreover, a set of differentially expressed proteins were identified, most of which were previously suggested to play a role in the development of DN, which further emphasizes the applicability of LC-MS/MS as a diagnostic tool.

Funding

  • Private Foundation Support