Comprehensive identification of stone-promoting proteins in the urine of kidney stone formers
2
Issued Date
2025-05-01
Resource Type
ISSN
01418130
eISSN
18790003
Scopus ID
2-s2.0-105002909548
Journal Title
International Journal of Biological Macromolecules
Volume
310
Rights Holder(s)
SCOPUS
Bibliographic Citation
International Journal of Biological Macromolecules Vol.310 (2025)
Suggested Citation
Hadpech S., Peerapen P., Rattananinsruang P., Detsangiamsak S., Phuangkham S., Chotikawanich E., Sritippayawan S., Thongboonkerd V. Comprehensive identification of stone-promoting proteins in the urine of kidney stone formers. International Journal of Biological Macromolecules Vol.310 (2025). doi:10.1016/j.ijbiomac.2025.143251 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/109810
Title
Comprehensive identification of stone-promoting proteins in the urine of kidney stone formers
Author's Affiliation
Corresponding Author(s)
Other Contributor(s)
Abstract
Urinary proteins have crucial roles in modulating kidney stone formation. While stone-inhibiting urinary proteins are well characterized, stone-promoting urinary proteins are insufficiently explored. This knowledge gap limits our ability to fully comprehend the pathogenic mechanisms underlying nephrolithiasis and hampers the development of targeted therapeutic/preventive interventions. Therefore, we systematically identified stone-promoting proteins from the urine of 30 calcium oxalate (CaOx) nephrolithiatic patients (stone formers). Urinary proteins were fractionated by anion exchange and size-exclusion chromatography. A total of 15 protein fractions (SF1-SF15) were tested for their modulating activities on CaOx crystals by various assays compared with the control. The fractions with net CaOx-promoting activities were then identified by nanoLC-ESI-Qq-TOF MS/MS. From 15 fractions, 9 had net CaOx-promoting activities in all crystal assays. Among 3–99 proteins identified from these fractions, alpha-1acid glycoprotein 2, alpha-1-antitrypsin, apolipoprotein D, CD44 antigen, endosialin, fibrinogen alpha chain, interleukin-18-binding protein, kallikrein-1, retinol-binding protein 4, and titin have been found to increase in the urine of stone formers compared with controls, reinforcing their potential roles as CaOx stone promoters. This study offers the largest collection of CaOx stone-promoting proteins that will shed light on pathogenic mechanisms of nephrolithiasis and may allow further development of new drug targets to treat/prevent nephrolithiasis.