{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T02:39:12Z","timestamp":1768012752000,"version":"3.49.0"},"reference-count":46,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T00:00:00Z","timestamp":1678838400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT","award":["UIDB\/04378\/2020"],"award-info":[{"award-number":["UIDB\/04378\/2020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>The inflammatory pathway driven by TNF-\u03b1, through its receptors TNFR1 and TNFR2, is a common feature in the pathogenesis of chronic kidney disease (CKD), regardless of the initial disease cause. Evidence correlates the chronic inflammatory status with decreased renal function. Our aim was to evaluate the potential of TNF receptors as biomarkers for CKD diagnosis and staging, as well as their association with the progression of renal lesions, in rat models of early and moderate CKD. We analyzed the circulating levels of inflammatory molecules\u2014tumor necrosis factor-alpha (TNF-\u03b1), tumor necrosis factor receptor 1 (TNFR1) and 2 (TNFR2) and tissue inhibitor of metalloproteinase-1 (TIMP-1)\u2014and studied their associations with TNFR1 and TNFR2 renal expression, glomerular and tubulointerstitial lesions, and with biomarkers of renal (dys)function. An increase in all inflammatory markers was observed in moderate CKD, as compared to controls, but only circulating levels of both TNFR1 and TNFR2 were significantly increased in the early disease; TNFR2 serum levels were negatively correlated with eGFR. However, only TNFR2 renal expression increased with CKD severity and showed correlations with the score of mild and advanced tubular lesions. Our findings suggest that renal TNFR2 plays a role in CKD development, and has potential to be used as a biomarker for the early detection and progression of the disease. Still, the potential value of this biomarker in disease progression warrants further investigation.<\/jats:p>","DOI":"10.3390\/biom13030534","type":"journal-article","created":{"date-parts":[[2023,3,15]],"date-time":"2023-03-15T06:36:36Z","timestamp":1678862196000},"page":"534","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["TNFR2 as a Potential Biomarker for Early Detection and Progression of CKD"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8257-5841","authenticated-orcid":false,"given":"Irina","family":"Lousa","sequence":"first","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3401-9554","authenticated-orcid":false,"given":"Fl\u00e1vio","family":"Reis","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology & Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-075 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1316-1319","authenticated-orcid":false,"given":"Sofia","family":"Viana","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology & Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-075 Coimbra, Portugal"},{"name":"Polytechnic Institute of Coimbra, ESTESC-Coimbra Health School, Pharmacy, 3046-854 Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9287-4068","authenticated-orcid":false,"given":"Pedro","family":"Vieira","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology & Experimental Therapeutics & Coimbra Institute for Clinical and Biomedical Research (iCBR), Faculty of Medicine, University of Coimbra, 3000-548 Coimbra, Portugal"},{"name":"Center for Innovative Biomedicine and Biotechnology (CIBB), University of Coimbra, 3004-504 Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra (CACC), 3000-075 Coimbra, Portugal"},{"name":"Polytechnic Institute of Coimbra, ESTESC-Coimbra Health School, Pharmacy, 3046-854 Coimbra, Portugal"}]},{"given":"Helena","family":"Vala","sequence":"additional","affiliation":[{"name":"CERNAS, Escola Superior Agr\u00e1ria de Viseu, Instituto Polit\u00e9cnico de Viseu, Campus Polit\u00e9cnico, 3504-510 Viseu, Portugal"},{"name":"Centre for the Research and Technology of Agro-Environmental and Biological Sciences (CITAB), University of Tr\u00e1s-os-Montes e Alto Douro, 5001-801 Vila Real, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3941-6850","authenticated-orcid":false,"given":"Lu\u00eds","family":"Belo","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]},{"given":"Alice","family":"Santos-Silva","sequence":"additional","affiliation":[{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"},{"name":"UCIBIO\u2014Applied Molecular Biosciences Unit, Laboratory of Biochemistry, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, 4050-313 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.kisu.2021.11.003","article-title":"Epidemiology of chronic kidney disease: An update 2022","volume":"12","author":"Kovesdy","year":"2022","journal-title":"Kidney Int. 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