Abstract: FR-PO740

Urinary Extracellular Vesicle-Derived Markers for Steroid Resistant FSGS

Session Information

Category: Glomerular

  • 1004 Clinical/Diagnostic Renal Pathology and Lab Medicine

Authors

  • Rood, Ilse M., Radboud University Medical Center, Nijmegen, Gelderland, Netherlands
  • Merchant, Michael, University of Louisville Kidney Disease Program, Louisville, Kentucky, United States
  • Wilkey, Daniel Wade, University of Louisville Kidney Disease Program, Louisville, Kentucky, United States
  • Van der vlag, Johan, Radboud University Medical Center, Nijmegen, Gelderland, Netherlands
  • Wetzels, Jack F., Radboud University Medical Center, Nijmegen, Gelderland, Netherlands
  • Klein, Jon B., University of Louisville Kidney Disease Program, Louisville, Kentucky, United States
  • Deegens, Jeroen, Radboud University Medical Center, Nijmegen, Gelderland, Netherlands
Background

Urinary extracellular vesicles (uEV) contain many proteins that may serve as biomarkers in renal disease. We compared the proteome of uEV from patients with biopsy proven focal segmental glomerular sclerosis (FSGS) with a steroid resistant nephrotic syndrome (SRNS; n=3), FSGS with steroid sensitive nephrotic syndrome (SSNS; n=3), FSGS with a partial remission on steroids (PR; n=3), minimal change disease (MCD; n=3), secondary FSGS (n=3) and normal healthy controls (NC; n=3). We hypothesized that the proteome of uEV could reveal a marker to predict steroid resistance in patients with FSGS.

Methods

UEV were isolated and analyzed using a multiplexing approach (TMT-labeling) and LCMS methods (1D-RP-HPLC-ESI-LTQ-VELOS-Orbitrap and Proteome Discover Software).

Results

In total 503 different proteins were identified with at least two peptides (with peptide and protein threshold of 95% with a false discovery rate of 0.5%). Comparison of FSGS SRNS to SSNS (including FSGS-SSNS, PR and MCD) indicated changes (unadjusted t-test p<0.05) in abundance of 26 proteins. In FSGS SRNS 17 proteins were downregulated, of which four proteins without any overlap of abundance compared to SSNS, secondary FSGS and normal controls. Nine proteins were upregulated, of which three proteins without any overlap compared to SSNS, secondary FSGS and normal controls. Many of these are related to the complement system.

Conclusion

We identified 26 extracellular vesicle-derived proteins that were significantly different between FSGS SRNS, compared to SSNS. Further analysis will be conducted to identify (a subset of) proteins that maybe considered as candidate biomarkers for FSGS SRNS.