Evidence map›Paper›PMID 40414344›Full record

ArticleJournal of advanced research2026

Urinary proteins from stone formers promote calcium oxalate crystallization, growth and aggregation via oxidative modifications.

Sudarat Hadpech, Paleerath Peerapen, Sakdithep Chaiyarit, Suchai Sritippayawan, Visith Thongboonkerd

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Article in Journal of advanced research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

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6citing papers in PubMed
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1 · What the graph read from it

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3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

5 authors.

Sudarat HadpechMedical Proteomics Unit, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Paleerath PeerapenMedical Proteomics Unit, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Sakdithep ChaiyaritMedical Proteomics Unit, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Suchai SritippayawanDivision of Nephrology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand.
Visith ThongboonkerdMedical Proteomics Unit, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. Electronic address: thongboonkerd@dr.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionVarious urinary parameters are used for determining kidney stone risk. However, almost all of the widely used lithogenic indices rely on urinary concentrations of small molecules/ions and pH.

objectiveTo address whether urinary macromolecules (especially oxidatively modified proteins) also play a critical role in determining the stone risk.

methodsComplexed urinary proteins (proteome) were purified from healthy individuals and calcium oxalate (CaOx) stone formers and performed various crystal assays and quantitative proteomics to compare them. Bioinformatic analyses were performed to gain additional insights, and the obtained data were verified by ELISA.

resultsWhile the normal urinary proteome inhibited CaOx stone-forming mechanisms (i.e., crystallization, growth and aggregation), the stone formers' urinary proteome promoted all these CaOx crystal parameters. Descriptive proteomics by nanoLC-ESI-LTQ-Orbitrap-MS/MS analysis identified 203 and 381 proteins in the urine of healthy individuals and stone formers, respectively. Analyses of physicochemical properties revealed only molecular mass and isoelectric point that slightly increased in the stone formers' urine, whereas instability index, grand average of hydrophathicity (GRAVY) and amino acid composition were comparable. Interestingly, proportion of oxidatively modified proteins (particularly those with methionine oxidation, methionine dioxidation and cysteine trioxidation) markedly increased (∼2.5-fold) in the stone formers' urine. Quantitative proteomics revealed 89 increased and 56 decreased proteins in the stone formers' urine. The oxidized proteins had a greater proportion (>3-fold) in the increased proteins (77 %) compared with the decreased ones (23 %), whereas the non-oxidized proteins showed comparable proportions (54 % and 46 %, respectively). Functional enrichment analyses revealed a correlation between the increased proteins and oxidative stress biological processes and molecular functions. Finally, ELISA confirmed the significantly increased levels of oxidized proteins in the stone formers' urine compared with that of healthy individuals.

conclusionThese data implicate that oxidatively modified proteome serves as a key pathogenic factor or risk for CaOx kidney stone formation.

Indexed as

Calcium OxalateKidney CalculiAdultCrystallizationFemaleHumansMaleMiddle AgedOxidation-ReductionProteomeProteomicsCalcium OxalateProteomeNephrolithiasisOxidized proteinRisk factorStone modulatorUrinary proteinUrolithiasis

Identifiers

PMID40414344
PMCPMC12958210

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.