{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:05:29Z","timestamp":1760148329779,"version":"build-2065373602"},"reference-count":17,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2023,4,23]],"date-time":"2023-04-23T00:00:00Z","timestamp":1682208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Left ventricular hypertrophy (LVH), which is a pervasive complication of end-stage kidney disease (ESKD), persists in some uremic individuals even after kidney transplantation (Ktx), contributing to worsening CV outcomes. Marinobufagenin (MBG), an endogenous steroid cardiotonic hormone endowed with natriuretic and vasoconstrictive properties, is an acknowledged trigger of uremic cardiomyopathy. However, its clinical significance in the setting of Ktx remains undefined. Methods: In a cohort of chronic Ktx recipients (n = 40), we assessed circulating MBG together with a thorough clinical and echocardiographic examination. Forty matched haemodialysis (HD) patients and thirty healthy subjects served as controls for MBG measurements. Patients were then prospectively followed up to 12 months and the occurrence of an established cardio-renal endpoint (death, CV events, renal events, graft rejection) was recorded. Results: Median MBG plasma levels were lower in Ktx as compared with HD patients (p = 0.02), but higher as compared with healthy controls (p = 0.0005). Urinary sodium (\u03b2 = 0.423; p = 0.01) and eGFR (\u03b2 = \u22120.324; p = 0.02) were the sole independent predictors of MBG in this cohort, while a strong correlation with left ventricular mass index (LVMi), found in univariate analyses (R = 0.543; p = 0.0007), gained significance only in multivariate models not including eGFR. Logistic regression analyses indicated MBG as a significant predictor of the combined endpoint (OR 2.38 [1.10\u20135.12] per each 1 nmoL\/L increase; p = 0.01), as well as eGFR, LVMi, serum phosphate and proteinuria. Conclusions: Ktx recipients display altered MBG levels which are influenced by sodium balance, renal impairment and the severity of LVH. Thus, MBG might represent an important missing link between reduced graft function and pathological cardiac remodelling and may hold important prognostic value for improving cardio-renal risk assessment.<\/jats:p>","DOI":"10.3390\/jcm12093072","type":"journal-article","created":{"date-parts":[[2023,4,24]],"date-time":"2023-04-24T02:31:05Z","timestamp":1682303465000},"page":"3072","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Marinobufagenin, Left Ventricular Hypertrophy and Residual Renal Function in Kidney Transplant Recipients"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3032-245X","authenticated-orcid":false,"given":"Davide","family":"Bolignano","sequence":"first","affiliation":[{"name":"Nephrology and Dialysis Unit, University \u201cMagna-Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Department of Medical and Surgical Sciences, University \u201cMagna-Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4192-3891","authenticated-orcid":false,"given":"Marta","family":"Greco","sequence":"additional","affiliation":[{"name":"Clinical Pathology Lab, University \u201cMagna-Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Department of Health Sciences, University \u201cMagna-Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierangela","family":"Presta","sequence":"additional","affiliation":[{"name":"Nephrology and Dialysis Unit, University \u201cMagna-Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alfredo","family":"Caglioti","sequence":"additional","affiliation":[{"name":"Nephrology and Dialysis Unit, University \u201cMagna-Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nazareno","family":"Carullo","sequence":"additional","affiliation":[{"name":"Nephrology and Dialysis Unit, University \u201cMagna-Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariateresa","family":"Zicarelli","sequence":"additional","affiliation":[{"name":"Nephrology and Dialysis Unit, University \u201cMagna-Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9536-5736","authenticated-orcid":false,"given":"Daniela Patrizia","family":"Foti","sequence":"additional","affiliation":[{"name":"Clinical Pathology Lab, University \u201cMagna-Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Department of Clinical and Experimental Medicine, University \u201cMagna-Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Dragone","sequence":"additional","affiliation":[{"name":"Clinical Pathology Lab, University \u201cMagna-Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7974-3792","authenticated-orcid":false,"given":"Michele","family":"Andreucci","sequence":"additional","affiliation":[{"name":"Nephrology and Dialysis Unit, University \u201cMagna-Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Department of Health Sciences, University \u201cMagna-Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8000-0681","authenticated-orcid":false,"given":"Giuseppe","family":"Coppolino","sequence":"additional","affiliation":[{"name":"Nephrology and Dialysis Unit, University \u201cMagna-Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"},{"name":"Department of Health Sciences, University \u201cMagna-Graecia\u201d of Catanzaro, 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,4,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"729","DOI":"10.1056\/NEJMra2014530","article-title":"Long-Term Survival after Kidney Transplantation","volume":"385","author":"Hariharan","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1046\/j.1523-1755.2000.00816.x","article-title":"Long-term survival in renal transplant recipients with graft function","volume":"57","author":"Ojo","year":"2000","journal-title":"Kidney Int."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1682","DOI":"10.1093\/ndt\/gfh283","article-title":"Left ventricular hypertrophy after renal transplantation: New approach to a deadly disorder","volume":"19","author":"Hernandez","year":"2004","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2440","DOI":"10.1046\/j.1432-1033.2002.02911.x","article-title":"Endogenous cardiac glycosides, a new class of steroid hormones","volume":"269","author":"Schoner","year":"2002","journal-title":"Eur. J. Biochem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1097\/FJC.0000000000000730","article-title":"Cardiotonic Steroids Induce Vascular Fibrosis Via Pressure-Independent Mechanism in NaCl-Loaded Diabetic Rats","volume":"74","author":"Fedorova","year":"2019","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1161\/01.HYP.0000252409.36927.05","article-title":"Marinobufagenin stimulates fibroblast collagen production and causes fibrosis in experimental uremic cardiomyopathy","volume":"49","author":"Elkareh","year":"2007","journal-title":"Hypertension"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Keppel, M.H., Piecha, G., M\u00e4rz, W., Cadamuro, J., Auer, S., Felder, T.K., Mrazek, C., Oberkofler, H., Trummer, C., and Gr\u00fcbler, M.R. (2019). The endogenous cardiotonic steroid Marinobufagenin and decline in estimated glomerular filtration rate at follow-up in patients with arterial hypertension. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0212973"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2581","DOI":"10.1007\/s11255-022-03161-0","article-title":"Marinobufagenin, left ventricular geometry and cardiac dysfunction in end-stage kidney disease patients","volume":"54","author":"Bolignano","year":"2022","journal-title":"Int. Urol. Nephrol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1093\/ehjci\/jev014","article-title":"Recommendations for cardiac chamber quantification by echocardiography in adults: An update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging","volume":"16","author":"Lang","year":"2015","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1053\/j.ajkd.2010.01.023","article-title":"Emerging role of the bufadienolides in cardiovascular and kidney diseases","volume":"56","author":"Puschett","year":"2010","journal-title":"Am. J. Kidney Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1159\/000363301","article-title":"The role of cardiotonic steroids in the pathogenesis of cardiomyopathy in chronic kidney disease","volume":"128","author":"Pavlovic","year":"2014","journal-title":"Nephron Clin. Pract."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1053\/j.ackd.2014.12.005","article-title":"Endogenous cardiotonic steroids in kidney failure: A review and an hypothesis","volume":"22","author":"Hamlyn","year":"2015","journal-title":"Adv. Chronic Kidney Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1124\/pr.108.000711","article-title":"Endogenous cardiotonic steroids: Physiology, pharmacology, and novel therapeutic targets","volume":"61","author":"Bagrov","year":"2009","journal-title":"Pharmacol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.31083\/j.rcm2204163","article-title":"Altered circulating marinobufagenin levels and recurrent intradialytic hypotensive episodes in chronic hemodialysis patients: A pilot, prospective study","volume":"22","author":"Bolignano","year":"2021","journal-title":"Rev. Cardiovasc. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1016\/S0140-6736(13)60595-4","article-title":"Chronic kidney disease and cardiovascular risk: Epidemiology, mechanisms, and prevention","volume":"382","author":"Gansevoort","year":"2013","journal-title":"Lancet"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"F637","DOI":"10.1152\/ajprenal.00046.2018","article-title":"Plasma marinobufagenin immunoreactivity in patients with chronic kidney disease: A case control study","volume":"315","author":"Piecha","year":"2018","journal-title":"Am. J. Physiol.-Renal Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1161\/CIRCHEARTFAILURE.114.001976","article-title":"Elevated Plasma Marinobufagenin, An Endogenous Cardiotonic Steroid, Is Associated With Right Ventricular Dysfunction and Nitrative Stress in Heart Failure","volume":"8","author":"Kennedy","year":"2015","journal-title":"Circ. Heart Fail."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/9\/3072\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:21:56Z","timestamp":1760124116000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/9\/3072"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,23]]},"references-count":17,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["jcm12093072"],"URL":"https:\/\/doi.org\/10.3390\/jcm12093072","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2023,4,23]]}}}