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

• Published in: Nephron (2015) Vol. 141; no. 3; p. 177
• Main Authors: Morikawa, Yukie, Takahashi, Naoki, Kamiyama, Kazuko, Nishimori, Kazuhisa, Nishikawa, Yudai, Morita, Sayu, Kobayashi, Mamiko, Fukushima, Sachiko, Yokoi, Seiji, Mikami, Daisuke, Kimura, Hideki, Kasuno, Kenji, Yashiki, Tetsuya, Naiki, Hironobu, Hara, Masanori, Iwano, Masayuki
• Format: Journal Article
• Language: English
• Published: Switzerland 01-01-2019
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers - urine; Calcium-Binding Proteins - urine; Extracellular Vesicles - metabolism; Female; Glomerulonephritis - urine; Humans; Male; Middle Aged; Young Adult; Crescentic glomerulonephritis; Extracellular vesicles; Podocytes; Soluble CD163; Fibroblast-specific protein 1; Podocalyxin
• ISSN: 2235-3186
• DOI: 10.1159/000495217

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.
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.
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).
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.