{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:49:43Z","timestamp":1782272983998,"version":"3.54.5"},"reference-count":81,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T00:00:00Z","timestamp":1782172800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100009687","name":"Ministry of Health subvention","doi-asserted-by":"publisher","award":["SUBZ.D020.26.036"],"award-info":[{"award-number":["SUBZ.D020.26.036"]}],"id":[{"id":"10.13039\/501100009687","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The endothelin system is critical in chronic kidney disease (CKD) pathogenesis. However, the relative contribution of circulating endothelin-related biomarkers versus genetic variability remains unclear, particularly in diabetic nephropathy (DN) and after kidney transplantation (KTx). This study evaluated plasma concentrations of endothelin-1 (ET-1), endothelin A receptor (ETAR), and anti-ETAR antibodies (ETAR-Ab) in healthy controls, diabetic nephropathy (DN) patients, and DN patients after kidney transplantation (post-KTx). The influence of polymorphisms rs5370 (EDN1) and rs5333 (EDNRA) on endothelin-related parameters was analyzed. Polymorphisms were genotyped via PCR-RFLP, and endothelial-related parameters were determined by ELISA. Significant endothelin system activation was observed in both DN and post-KTx patients. ET-1 and ETAR concentrations were markedly elevated compared to controls, with the highest ET-1 levels detected in the post-KTx group, whereas ETAR-Ab levels were reduced. A sex-specific association for rs5370 was observed in male patients with the TG genotype (a nearly 4.5-fold higher risk of renal replacement therapy than in female patients). In proteinuric DN patients, the TC genotype (rs5333) was associated with elevated ETAR and ETAR-Ab. Endothelin system dysregulation is a prominent and persistent feature of CKD, noted after kidney transplantation. The endothelin activation, observed in transplant patients particularly, highlights the potential clinical relevance of endothelin-related biomarkers and supports the rationale for therapeutic strategies targeting the endothelin pathway, including endothelin receptor antagonists.<\/jats:p>","DOI":"10.3390\/ijms27135647","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T03:09:17Z","timestamp":1782270557000},"page":"5647","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Activation of the Endothelin System in Chronic Kidney Disease and Kidney Transplant Recipients\u2014Implications for Disease Progression"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8976-6683","authenticated-orcid":false,"given":"Milena","family":"\u015aciskalska","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Kr\u00f3l-Kulikowska","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Grzybowska","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Transplantation Medicine and Internal Diseases, Institute of Internal Diseases, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3906-8739","authenticated-orcid":false,"given":"Ewa","family":"Tabaka","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Transplantation Medicine and Internal Diseases, Institute of Internal Diseases, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4122-7469","authenticated-orcid":false,"given":"Wiktoria","family":"Pabian","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Transplantation Medicine and Internal Diseases, Institute of Internal Diseases, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-5046-3464","authenticated-orcid":false,"given":"Dominika","family":"Pisarek","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Transplantation Medicine and Internal Diseases, Institute of Internal Diseases, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0293-7086","authenticated-orcid":false,"given":"Krzysztof","family":"Benc","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Transplantation Medicine and Internal Diseases, Institute of Internal Diseases, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2817-3689","authenticated-orcid":false,"given":"Magdalena","family":"Kuriata-Kordek","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Transplantation Medicine and Internal Diseases, Institute of Internal Diseases, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0588-1551","authenticated-orcid":false,"given":"Miros\u0142aw","family":"Banasik","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Transplantation Medicine and Internal Diseases, Institute of Internal Diseases, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0935-5663","authenticated-orcid":false,"given":"Marta","family":"Kepinska","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biochemistry, Faculty of Pharmacy, Wroclaw Medical University, 50-556 Wroclaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mallamaci, F., and Tripepi, G. 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