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Abstract: FR-PO1057

Elevated Levels of Urinary Extracellular Vesicle Fibroblast-Specific Protein 1 in Patients with Active Crescentic Glomerulonephritis

Session Information

Category: Glomerular Diseases

  • 1202 Glomerular Diseases: Immunology and Inflammation

Authors

  • Morikawa, Yukie, University of Fukui, Yoshida-gun, Japan
  • Takahashi, Naoki, University of Fukui, Yoshida-gun, Japan
  • Kamiyama, Kazuko, University of Fukui, Yoshida-gun, Japan
  • Nishimori, Kazuhisa, University of Fukui, Yoshida-gun, Japan
  • Nishikawa, Yudai, University of Fukui, Yoshida-gun, Japan
  • Kobayashi, Mamiko, University of Fukui, Yoshida-gun, Japan
  • Fukushima, Sachiko, University of Fukui, Yoshida-gun, Japan
  • Yokoi, Seiji, University of Fukui, Yoshida-gun, Japan
  • Mikami, Daisuke, University of Fukui, Yoshida-gun, Japan
  • Kimura, Hideki, University of Fukui, Yoshida-gun, Japan
  • Kasuno, Kenji, University of Fukui, Yoshida-gun, Japan
  • Hara, Masanori, Niigata Wellness (Iwamuro Health Promotion Center), Niigata, Japan
  • Iwano, Masayuki, University of Fukui, Yoshida-gun, Japan
Background

Extracellular vesicles (EVs), including exosomes, are present in a variety of bodily fluids, including urine. We previously reported that large numbers of fibroblast-specific protein 1 (FSP1)-expressing cells accumulate within damaged glomeruli and that urinary FSP1 could potentially serve as a biomarker of ongoing glomerular injury. However, the precise mechanism by which urinary FSP1 is secreted is unknown.

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), purified the urinary EVs using total exosome isolation regent, and characterized the vesicles using Nanosight, western blotting and immunoelectron microscopy. We measured FSP1 levels in total urine and EVs fraction with sandwich ELISA. FSP1 level associated with crescentic formation were evaluated by receiver operating characteristic (ROC) curve analysis.

Results

Deemed to be mainly exosomes, based on their size distribution, the vesicles contained FSP1. Moreover, a portion of these FSP1-positive EVs were also positive for podocalyxin. ELISAs showed that FSP1 levels in urinary EVs correlated positively with rates of biopsy-proven cellular crescent formation (r = 0.562, P < 0.001) and total crescent formation (r = 0.448, P = 0.005) among total glomeruli. FSP1 levels in urinary EVs were significantly higher in patients with cellular crescents affecting 20% or more of their glomeruli than in those with fewer affected glomeruli (P = 0.003). FSP1 level in EVs for predicting cellular crescent formation affecting more 20% was 2.4 ng/mL, with an area under the ROC curve were 0.88 (95%CI, 0.693 to 1.070). FSP1 levels in urinary EVs also correlated positively with total urinary FSP1 levels (r = 0.834, P < 0.001) in patients with at least one cellular crescent.

Conclusion

These data suggest that a portion of urinary FSP1 is secreted as microvesicles originating from podocytes, and that FSP1 levels in urinary EVs reflect active and ongoing glomerular injury, such as cellular crescent formation.