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

Abstract

BACKGROUND/AIMS:

Extracellular vesicles (EVs), including exosomes, are present in various bodily fluids, including urine. We and others previously reported that cells expressing fibroblast-specific protein 1 (FSP1) accumulate within damaged glomeruli, and that urinary FSP1, as well as urinary soluble CD163, could potentially serve as a biomarker of ongoing glomerular injury.

METHODS:

To test that idea, we collected urine samples from 37 patients with glomerular disease; purified the urinary EVs; characterized them using Nanosight, western blotting, and immunoelectron microscopy; and determined FSP1 and soluble CD163 levels using enzyme-linked immunosorbent assays.

RESULTS:

Deemed to be mainly exosomes based on their size distribution, the EVs in urine contained FSP1, and a portion of the FSP1-positive vesicles was also positive for podocalyxin. FSP1 levels in urinary EVs were (1) positively correlated 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; (2) significantly higher in patients with cellular crescents affecting 20% or more of their glomeruli than in those with fewer affected glomeruli (p = 0.003); and (3) significantly decreased after glucocorticoid and immunosuppressant therapy (p < 0.05). A positive correlation between FSP1 levels in urinary EVs and urinary soluble CD163 levels was confirmed (r = 0.367, p < 0.05).

CONCLUSION:

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

• Authors: Yukie Morikawa, Naoki Takahashi, Kazuko Kamiyama, Kazuhisa Nishimori, Yudai Nishikawa, Sayu Morita, Mamiko Kobayashi, Sachiko Fukushima, Seiji Yokoi, Daisuke Mikami, Hideki Kimura, Kenji Kasuno, Tetsuya Yashiki, Hironobu Naiki, Masanori Hara, Masayuki Iwano
• Journal: Nephron (Nephron) Vol. 141 Issue 3 Pg. 177-187 ( 2019) ISSN: 2235-3186 [Electronic] Switzerland
• PMID: 30540988 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 S. Karger AG, Basel.

Chemical References

• Biomarkers
• Calcium-Binding Proteins
• S100 Calcium-Binding Protein A4
• S100A4 protein, human

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Biomarkers (urine)
• Calcium-Binding Proteins (urine)
• Extracellular Vesicles (metabolism)
• Female
• Glomerulonephritis (urine)
• Humans
• Male
• Middle Aged
• S100 Calcium-Binding Protein A4
• Young Adult