Differences of Uric Acid Transporters Carrying Extracellular Vesicles in the Urine from Uric Acid and Calcium Stone Formers and Non-Stone Formers
Background: Low urine pH and volume are established risk factors for uric acid (UA) stone disease (UASD). Renal tubular epithelial cells exposed to an acidic pH and/or UA crystals can shed extracellular vesicles (EVs) into the tubular fluid, and these EVs may be a pathogenic biomarker of UASD. Metho...
Main Authors: | , , , , |
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Format: | Article |
Language: | English |
Published: |
MDPI AG
2022-09-01
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Series: | International Journal of Molecular Sciences |
Subjects: | |
Online Access: | https://www.mdpi.com/1422-0067/23/17/10010 |
Summary: | Background: Low urine pH and volume are established risk factors for uric acid (UA) stone disease (UASD). Renal tubular epithelial cells exposed to an acidic pH and/or UA crystals can shed extracellular vesicles (EVs) into the tubular fluid, and these EVs may be a pathogenic biomarker of UASD. Methods: Urinary EVs bearing UA transporters (SLC2A9, SLC17A3, SLC22A12, SLC5A8, ABCG2, and ZNF365) were quantified in urine from UA stone formers (UASFs), calcium stone formers (CSFs), and age-/sex-matched non-stone formers (NSFs) using a standardized and published method of digital flow cytometry. Results: Urinary pH was lower (<i>p</i> < 0.05) and serum and urinary UA were greater (<i>p</i> < 0.05) in UASFs compared with NSFs. Urinary EVs carrying SLC17A3 and SLC5A8 were lower (<i>p</i> < 0.05) in UASFs compared with NSFs. Urinary EVs bearing SLC2A9, SLC22A12, SLC5A8, ABCG2, and ZNF365 were lower (<i>p</i> < 0.05) in CSFs than UASFs, while excretion of SLC17A3-bearing EVs did not differ between groups. Conclusion: EVs bearing specific UA transporters might contribute to the pathogenesis of UASD and represent non-invasive pathogenic biomarkers for calcium and UA stone risk. |
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ISSN: | 1661-6596 1422-0067 |