{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:47:29Z","timestamp":1791002849415,"version":"4.1.0"},"reference-count":38,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T00:00:00Z","timestamp":1646611200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Center of Excellence for Reproductive and Regenerative Medicine (project \u201cReproductive and regenerative medicine\u2014exploration of new platforms and potentials","award":["KK.01.1.1.01.0008"],"award-info":[{"award-number":["KK.01.1.1.01.0008"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background: We have previously shown that metzincin protease ADAMTS-4 accompanies renal fibrogenesis, as it appears in the blood of hemodialysis patients. Methods: Native kidney (NKB) and kidney transplant (TXCI) biopsy samples as well as plasma from patients with various stages of CKD were compared to controls. In paired analysis, 15 TXCI samples were compared with their zero-time biopsies (TX0). Tissues were evaluated and scored (interstitial fibrosis and tubular atrophy (IFTA) for NKB and Banff ci for TXCI). Immunohistochemical (IHC) staining for ADAMTS-4 and BMP-1 was performed. Plasma ADAMTS-4 was detected using ELISA. Results: ADAMTS-4 IHC expression was significantly higher in interstitial compartment (INT) of NKB and TXCI group in peritubular capillaries (PTC) and interstitial stroma (INT). Patients with higher stages of interstitial fibrosis (ci &gt; 1 and IFTA &gt; 1) expressed ADAMTS-4 in INT more frequently in both groups (p = 0.005; p = 0.013; respectively). In paired comparison, TXCI samples expressed ADAMTS-4 in INT and PTC more often than TX0. ADAMTS-4 plasma concentration varied significantly across CKD stages, being highest in CKD 2 and 3 compared to other groups (p = 0.0064). Hemodialysis patients had higher concentrations of ADAMTS-4 compared to peritoneal dialysis (p &lt; 0.00001). Conclusion: ADAMTS-4 might have a significant role in CKD as a potential novel diagnostic indicator.<\/jats:p>","DOI":"10.3390\/diagnostics12030648","type":"journal-article","created":{"date-parts":[[2022,3,7]],"date-time":"2022-03-07T10:21:16Z","timestamp":1646648476000},"page":"648","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["First Characterization of ADAMTS-4 in Kidney Tissue and Plasma of Patients with Chronic Kidney Disease\u2014A Potential Novel Diagnostic Indicator"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7781-1678","authenticated-orcid":false,"given":"Ivana Kovacevic","family":"Vojtusek","sequence":"first","affiliation":[{"name":"Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Center Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0240-4178","authenticated-orcid":false,"given":"Mario","family":"Laganovic","sequence":"additional","affiliation":[{"name":"Department of Nephrology, University Hospital Merkur, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2781-4576","authenticated-orcid":false,"given":"Marija","family":"Burek Kamenaric","sequence":"additional","affiliation":[{"name":"Tissue Typing Center, Clinical Department for Transfusion Medicine and Transplantation Biology, University Hospital Center Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stela","family":"Bulimbasic","sequence":"additional","affiliation":[{"name":"Clinical Department of Pathology and Cytology, University Hospital Center Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stela","family":"Hrkac","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine, University Hospital Center Zagreb, 10000 Zagreb, Croatia"},{"name":"Center for Translational and Clinical Research, Department of Proteomics, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7782-1646","authenticated-orcid":false,"given":"Grgur","family":"Salai","sequence":"additional","affiliation":[{"name":"Center for Translational and Clinical Research, Department of Proteomics, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Teaching Institute of Emergency Medicine of the City of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanja","family":"Ivkovic","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Arterial Hypertension, Dialysis and Transplantation, University Hospital Center Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Public Health, Faculty of Health Studies, University of Rijeka, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijana","family":"Coric","sequence":"additional","affiliation":[{"name":"Clinical Department of Pathology and Cytology, University Hospital Center Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5920-4169","authenticated-orcid":false,"given":"Rudjer","family":"Novak","sequence":"additional","affiliation":[{"name":"Center for Translational and Clinical Research, Department of Proteomics, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9814-3178","authenticated-orcid":false,"given":"Lovorka","family":"Grgurevic","sequence":"additional","affiliation":[{"name":"Center for Translational and Clinical Research, Department of Proteomics, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"},{"name":"Department of Anatomy, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,7]]},"reference":[{"key":"ref_1","unstructured":"GBD Chronic Kidney Disease Collaboration (2020). 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Int."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/3\/648\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T22:33:20Z","timestamp":1760135600000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/12\/3\/648"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,7]]},"references-count":38,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2022,3]]}},"alternative-id":["diagnostics12030648"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics12030648","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,7]]}}}