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Abstract: FR-PO826

Difference Between Urinary Vesicle Fibroblast Specific Protein 1 and Urinary-Soluble CD163 as a Marker of Crescent Formation

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Morikawa, Yukie, University of Fukui, Fukui, Japan
  • Takahashi, Naoki, University of Fukui, Fukui, Japan
  • Kamiyama, Kazuko, University of Fukui, Fukui, Japan
  • Nishikawa, Sho, University of Fukui, Fukui, Japan
  • Nishimori, Kazuhisa, University of Fukui, Fukui, Japan
  • Nishikawa, Yudai, University of Fukui, Fukui, Japan
  • Kobayashi, Mamiko, University of Fukui, Fukui, Japan
  • Fukushima, Sachiko, University of Fukui, Fukui, Japan
  • Yokoi, Seiji, University of Fukui, Fukui, Japan
  • Mikami, Daisuke, University of Fukui, Fukui, Japan
  • Kimura, Hideki, University of Fukui, Fukui, Japan
  • Kasuno, Kenji, University of Fukui, Fukui, Japan
  • Iwano, Masayuki, University of Fukui, Fukui, Japan
Background

Extracellular vesicles (EVs) are present in urine. We previously reported that fibroblast-specific protein 1 (FSP1) levels in urinary EVs (U-EVs) reflect active and ongoing glomerular injury, such as cellular crescent formation. However, it is unknown whether FSP1 in U-EVs is superior to urinary soluble CD163 (U-sCD163) which was established as a biomarker of crescentic glomerulonephritis.

Methods

To address that issue, we collected urine samples from 37 patients with various types of glomerular disease (6 with ANCA-associated nephritis, 11 with IgA nephropathy, 11 with membranous nephropathy, 6 with minimal-change disease and 3 with lupus nephritis), and purified U-EVs using total exosome isolation regent. We measured FSP1 levels in U-EVs and sCD163 levels in total urine using ELISAs and analyzed correlation between FSP1 or sCD163 levels and rates of biopsy-proven crescent formation. To determine whether FSP1 and sCD163 levels were associated with crescentic formation, we used receiver operating characteristic (ROC) curve analysis.

Results

FSP1 levels in U-EVs correlated positively with U-sCD163 levels (r=0.367, P<0.05). FSP1 levels in U-EVs also correlated positively with rates of biopsy-proven cellular crescent formation (r=0.562, P<0.001). Meanwhile, U-sCD163 levels correlated positively with rates of biopsy-proven cellular (r=0.595, P<0.001), fibrocellular (r=0.511, P<0.001), and fibrous (r=0.501, P<0.001) crescent formation. FSP1 levels in U-EVs and U-sCD163 levels for predicting cellular crescent formation affecting more than 20% of total glomeruli was 2.4 µg/gCr and 14.5 ng/mgCr, respectively, with an area under the ROC curve were 0.88 (95%CI, 0.693 to 1.070) and 0.82 (95%CI, 0.673 to 0.961) (P=0.58). Both U-sCD163 levels and FSP1 levels in U-EVs were significantly reduced after treatment (median: 4.90 to 0.35 ng/mgCr, mean: 2.72 to 0.14 µg/gCr).

Conclusion

These data suggest that both FSP1 in U-EVs and U-sCD163 are available biomarkers of active and ongoing glomerular injury, such as crescent formation. However, it was FSP1 level in U-EVs that specifically reflected cellular crescent formation requiring urgent treatment.

Funding

  • Government Support - Non-U.S.