{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:09:29Z","timestamp":1790086169200,"version":"4.0.1"},"reference-count":52,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T00:00:00Z","timestamp":1739836800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Research Fund","award":["TTK200219505766"],"award-info":[{"award-number":["TTK200219505766"]}]},{"name":"National Research Fund","award":["040125"],"award-info":[{"award-number":["040125"]}]},{"name":"Discovery Academic Fellowship","award":["TTK200219505766"],"award-info":[{"award-number":["TTK200219505766"]}]},{"name":"Discovery Academic Fellowship","award":["040125"],"award-info":[{"award-number":["040125"]}]},{"name":"Bongani Mayosi Netcare Clinician Scholarship, and DIPLOMICS","award":["TTK200219505766"],"award-info":[{"award-number":["TTK200219505766"]}]},{"name":"Bongani Mayosi Netcare Clinician Scholarship, and DIPLOMICS","award":["040125"],"award-info":[{"award-number":["040125"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Kidney function parameters including estimated glomerular filtration rate (eGFR) and urine albumin excretion are commonly used to diagnose chronic kidney disease (CKD). However, these parameters are relatively insensitive, limiting their utility for screening and early detection of kidney disease. Studies have suggested that urinary proteomic profiles differ by eGFR stage, offering potential insights into kidney disease pathogenesis alongside opportunities to increase the sensitivity of current testing strategies. In this study, we characterized and compared the urinary proteome across different eGFR stages in a Black African cohort from rural Mpumalanga Province, South Africa. We stratified 81 urine samples by eGFR stage (mL\/min\/1.73 m2): Stage G1 (eGFR \u2265 90; n = 36), Stage G2 (eGFR 60\u201389; n = 35), and Stage G3\u2013G5 (eGFR &lt; 60; n = 10). Urine proteomic analysis was performed using an Evosep One liquid chromatography system coupled to a Sciex 5600 TripleTOF in data-independent acquisition mode. Nonparametric multivariate analysis and receiver operating characteristic (ROC) curves were used to assess the performance of differentially abundant proteins (DAPs). Pathway analysis was performed on DAPs. Creatinine-based eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. In this study, thirty-eight urinary proteins were differentially abundant for eGFR Stages 3\u20135 when compared to Stages G1 (AUC = 0.95; CI: 0.86\u20131) and G2 (AUC = 0.84; CI: 0.64\u20130.98). Notably, only six urinary proteins (Cystatin M (CST6), glutathione hydrolase 6 (GGT6), sushi domain containing 2 (SUSD2), insulin-like growth factor binding protein 6 (IGFBP6), heat shock protein 90 beta family member 1 (HSP90B1), and mannosidase alpha class 1A member 1 (MAN1A1)) were differentially abundant when comparing Stage G1 and Stage G2 with a modest AUC = 0.81 (CI: 0.67\u20130.92). Pathway analysis indicated that DAPs were associated with haemostasis and fibrin clot formation. In a rural cohort from South Africa, the urinary proteome differed by eGFR stage, and we identified six differentially abundant proteins which, in combination, could help to differentiate earlier eGFR stages with higher predictive accuracy than the currently available tests.<\/jats:p>","DOI":"10.3390\/ijms26041740","type":"journal-article","created":{"date-parts":[[2025,2,18]],"date-time":"2025-02-18T06:41:12Z","timestamp":1739860872000},"page":"1740","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Distinct Urinary Proteome Changes Across Estimated Glomerular Filtration Rate Stages in a Cohort of Black South Africans"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8068-7460","authenticated-orcid":false,"given":"Siyabonga","family":"Khoza","sequence":"first","affiliation":[{"name":"Department of Chemical Pathology, National Health Laboratory Service, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaya A.","family":"George","sequence":"additional","affiliation":[{"name":"National Health Laboratory Service, Johannesburg 2192, South Africa"},{"name":"Academic Affairs, Research & Quality Assurance, National Health Laboratory Service, Johannesburg 2000, South Africa"},{"name":"Wits Diagnostic Innovation Hub, University of the Witwatersrand, Johannesburg 2000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Previn","family":"Naicker","sequence":"additional","affiliation":[{"name":"ReSyn Biosciences, Edenvale 1610, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stoyan H.","family":"Stoychev","sequence":"additional","affiliation":[{"name":"Evosep Biosystems, 5230 Odense, Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rethabile J.","family":"Mokoena","sequence":"additional","affiliation":[{"name":"Future Production Chemicals, Council for Scientific and Industrial Research, Pretoria 0001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5111-5970","authenticated-orcid":false,"given":"Ireshyn S.","family":"Govender","sequence":"additional","affiliation":[{"name":"ReSyn Biosciences, Edenvale 1610, South Africa"},{"name":"Future Production Chemicals, Council for Scientific and Industrial Research, Pretoria 0001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7130-9142","authenticated-orcid":false,"given":"June","family":"Fabian","sequence":"additional","affiliation":[{"name":"Wits Donald Gordon Medical Centre, School of Clinical Medicine, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa"},{"name":"South African Medical Research Council\/Wits University Rural Public Health and Health Transitions Research Unit (Agincourt), School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg 2000, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group (2024). 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