{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T15:01:26Z","timestamp":1780412486327,"version":"3.54.1"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nephrol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Type 4 cardiorenal syndrome (CRS) involves cardiovascular alterations caused by chronic kidney disease (CKD). Fibroblast growth factor-23 (FGF23), carboxy-terminal propeptide of procollagen type I (PIP), and parathyroid hormone (PTH) have been proposed as biomarkers of pathological cardiac remodeling in CKD. In contrast, it has been suggested that MicroRNA 221 has a cardioprotective role. Available evidence shows that, 12 months after kidney transplantation (KT), type 4 CRS reverts in only half of the patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objective<\/jats:title><jats:p>To assess long-term cardiac reverse remodeling after KT and its association with FGF23, PIP, and PTH levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients with end-stage renal disease were assessed before and 28 months after KT using FGF23, PIP, and PTH serum concentrations and transthoracic echocardiography.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Fifty-three patients were followed for 28 months after KT. All the patients showed cardiac abnormalities upon inclusion. A follow-up assessment showed a reduction in left ventricle (LV) mass (121 \u00b1 48 vs. 65 \u00b1 14 gr\/m<jats:sup>2<\/jats:sup>) and left atrial volume (46 vs. 30 ml\/m<jats:sup>2<\/jats:sup>). The LV ejection fraction (53 vs. 63%), LV global longitudinal strain (-15.9 vs.-19.4%), and LV diastolic function improved. miR-221 expression increased after KT (8.73 RIQ= 3.7-25 vs. 40.16 RIQ= 24-223, p=0.001) and was correlated with the Ee\u00b4ratio (r= -0.32, p= 0.02). Multivariate analysis showed that post-KT LV mass was determined by pre-KT LV mass, serum Cr level, post-KT PIP, and hypertension (R<jats:sup>2<\/jats:sup> = 0.65, F=12.1, p=0.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Contrary to other evidence, this study demonstrated that type 4 CRS is reversible over the long term. This is a paramount finding because KT normalizes cardiac structure and function independently of the severity of basal cardiac abnormalities.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneph.2024.1455036","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T06:52:33Z","timestamp":1741243953000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Role of kidney transplantation in long-term cardiac reverse remodeling and interconnecting mechanisms in type 4 cardiorenal syndrome"],"prefix":"10.3389","volume":"4","author":[{"given":"Jose Luis","family":"Salas-Pacheco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose Manuel","family":"Arreola-Guerra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Marquez-Velasco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israel","family":"Perez-Torres","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergio","family":"Casarez-Alvarado","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanny","family":"Fuentevilla-Alvarez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ver\u00f3nica","family":"Guarner-Lans","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall","family":"Cruz-Soto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Elena","family":"Soto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000664","article-title":"Cardiorenal syndrome: classification, pathophysiology, diagnosis, and treatment strategies: A scientific statement from the american heart association","volume":"139","author":"Rangaswami","year":"2019","journal-title":"Circulation"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1159\/000167018","article-title":"The cardiorenal syndrome","volume":"27","author":"Ronco","year":"2009","journal-title":"Blood Purif"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1097\/00000441-200304000-00003","article-title":"Cardiac performance and morphology in end-stage renal disease","volume":"325","author":"Alpert","year":"2003","journal-title":"Am J Med Sci"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/S1388-9842(99)00057-4","article-title":"Disorders of left ventricular structure and function in chronic uremia: how often, why and what to do with it","volume":"1","author":"Dyadyk","year":"1999","journal-title":"Eur J Heart Fail"},{"key":"B5","article-title":"Left ventricular diastolic function in patients on maintenance hemodialysis: comparison with hypertensive heart disease and hypertrophic cardiomyopathy","volume":"42","author":"Fujimoto","year":"1994","journal-title":"Clin Nephrol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2005.00086.x","article-title":"Clinical and pathologic characteristics of dilated cardiomyopathy in hemodialysis patients","volume":"67","author":"Aoki","year":"2005","journal-title":"Kidney Int"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1172\/JCI46122","article-title":"FGF23 induces left ventricular hypertrophy","volume":"121","author":"Faul","year":"2011","journal-title":"J Clin Invest"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0000000000000294","article-title":"FGF-23 and cardiovascular disease: review of literature","volume":"23","author":"Batra","year":"2016","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013050465","article-title":"Fibroblast growth factor-23 and cardiovascular events in CKD","volume":"25","author":"Scialla","year":"2014","journal-title":"J Am Soc Nephrol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfac220","article-title":"The direct effect of fibroblast growth factor 23 on vascular smooth muscle cell phenotype and function","volume":"38","author":"Vergara","year":"2023","journal-title":"Nephrol Dialysis Transplant"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.ehj.2003.09.010","article-title":"Parathyroid hormone and left ventricular hypertrophy","volume":"24","author":"Saleh","year":"2003","journal-title":"Eur Heart J"},{"key":"B12","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1016\/S0008-6363(97)00194-6","article-title":"Cardiovascular actions of parathyroid hormone and parathyroid hormone-related peptide","volume":"37","author":"Schl\u00fcter","year":"1998","journal-title":"Cardiovasc Res"},{"key":"B13","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1093\/ndt\/gfy140","article-title":"The expanding roles of microRNAs in kidney pathophysiology","volume":"34","author":"Metzinger-Le Meuth","year":"2019","journal-title":"Nephrol Dialysis Transplant"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.111.017954","article-title":"Novel microRNA prosurvival cocktail for improving engraftment and function of cardiac progenitor cell transplantation","volume":"124","author":"Hu","year":"2011","journal-title":"Circulation"},{"key":"B15","doi-asserted-by":"publisher","first-page":"296","DOI":"10.1177\/1074248415604463","article-title":"Discovery of potential therapeutic miRNA targets in cardiac ischemia\u2013reperfusion injury","volume":"21","author":"Zhou","year":"2016","journal-title":"J Cardiovasc Pharmacol Ther"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.117.10094","article-title":"MicroRNA-221\/222 family counteracts myocardial fibrosis in pressure overload\u2013induced heart failure","volume":"71","author":"Verjans","year":"2018","journal-title":"Hypertension"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2019.04.025","article-title":"Why clinicians should care about the cardiac interstitium","volume":"12","author":"Schelbert","year":"2019","journal-title":"JACC Cardiovasc Imaging"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/j.carpath.2011.10.001","article-title":"2011 Consensus statement on endomyocardial biopsy from the Association for European Cardiovascular Pathology and the Society for Cardiovascular Pathology","volume":"21","author":"Leone","year":"2012","journal-title":"Cardiovasc Pathol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.04.026","article-title":"Circulating biomarkers of myocardial fibrosis","volume":"65","author":"L\u00f3pez","year":"2015","journal-title":"J Am Coll Cardiol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2015.10.063","article-title":"Myocardial collagen cross-linking is associated with heart failure hospitalization in patients with hypertensive heart failure","volume":"67","author":"L\u00f3pez","year":"2016","journal-title":"J Am Coll Cardiol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2018.02.021","article-title":"Myocardial interstitial fibrosis in heart failure","volume":"71","author":"Gonz\u00e1lez","year":"2018","journal-title":"J Am Coll Cardiol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.01400308","article-title":"Renal transplantation is not associated with regression of left ventricular hypertrophy","volume":"3","author":"Patel","year":"2008","journal-title":"Clin J Am Soc Nephrol"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1097\/00007890-200212150-00016","article-title":"Cardiovascular effects of successful renal transplantation: a 1-year sequential study of left ventricular morphology and function, and 24-hour blood pressure profile1","volume":"74","author":"Ferreira","year":"2002","journal-title":"Transplantation"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.transproceed.2014.08.019","article-title":"Left ventricular hypertrophy in renal transplant recipients in the first year after transplantation","volume":"46","author":"\u015alubowska","year":"2014","journal-title":"Transplant Proc"},{"key":"B25","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ejim.2016.02.019","article-title":"Cardiorenal syndrome type 4: From chronic kidney disease to cardiovascular impairment","volume":"30","author":"Granata","year":"2016","journal-title":"Eur J Intern Med"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.echo.2014.10.003","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":"28","author":"Lang","year":"2015","journal-title":"J Am Soc Echocardiography"},{"key":"B27","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.echo.2016.01.011","article-title":"Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the american society of echocardiography and the european association of cardiovascular imaging","volume":"29","author":"Nagueh","year":"2016","journal-title":"J Am Soc Echocardiography"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of relative gene expression data using real-time quantitative PCR and the 2\u2013\u0394\u0394CT method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1053\/ajkd.1998.v32.pm9820470","article-title":"Epidemiology of cardiovascular disease in chronic renal disease","volume":"9","author":"Foley","year":"1998","journal-title":"J Am Soc Nephrol."},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000102971.85504.7c","article-title":"Kidney disease as a risk factor for development of cardiovascular disease","volume":"42","author":"Sarnak","year":"2003","journal-title":"Hypertension"},{"key":"B31","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1097\/TP.0b013e3181caeece","article-title":"Cardiovascular death after renal transplantation remains the first cause despite significant quantitative and qualitative changes","volume":"89","author":"Berthoux","year":"2010","journal-title":"Transplantation"},{"key":"B32","doi-asserted-by":"publisher","first-page":"481","DOI":"10.4103\/IJPM.IJPM_213_16","article-title":"Histological and morphometric analysis of dilated cardiomyopathy with special reference to collagen IV expression","volume":"60","author":"Jain","year":"2017","journal-title":"Indian J Pathol Microbiol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1007\/s10554-022-02543-w","article-title":"Exploring myocardial fibrosis in severe aortic stenosis: echo, CMR and histology data from FIB-AS study","volume":"38","author":"Bal\u010di\u016bnait\u0117","year":"2022","journal-title":"Int J Cardiovasc Imaging."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.carpath.2020.107256","article-title":"Histological features of endomyocardial biopsies in patients undergoing hemodialysis: Comparison with dilated cardiomyopathy and hypertensive heart disease","volume":"49","author":"Yoshizawa","year":"2020","journal-title":"Cardiovasc Pathol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"S95","DOI":"10.1097\/00004872-199609002-00018[39","article-title":"Regression of left ventricular hypertrophy as a surrogate end-point for morbid events in hypertension treatment trials","volume":"14","author":"Devereux","year":"1996","journal-title":"J Hypertens"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1007\/s11748-019-01188-2","article-title":"Left ventricular mass regression in patients without patient\u2013prosthesis mismatch after aortic valve replacement for aortic stenosis","volume":"68","author":"Hachiro","year":"2020","journal-title":"Gen Thorac Cardiovasc Surg"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1016\/S0895-7061(98)00024-7","article-title":"Time course of complete normalization of left ventricular hypertrophy during long-term antihypertensive therapy with angiotensin converting enzyme inhibitors","volume":"11","author":"Franz","year":"1998","journal-title":"Am J Hypertens"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1007\/s40119-022-00260-y","article-title":"Left ventricular hypertrophy: etiology-based therapeutic options","volume":"11","author":"Sayin","year":"2022","journal-title":"Cardiol Ther"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2019.05.018","article-title":"MicroRNA-221 is cardioprotective and antifibrotic in a rat model of myocardial infarction","author":"Zhou","year":"2019","journal-title":"Mol Ther Nucleic Acids"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.omtn.2020.09.041","article-title":"microRNA-221 inhibits latent TGF-\u03b21 activation through targeting thrombospondin-1 to attenuate kidney failure-induced cardiac fibrosis","volume":"22","author":"Zhou","year":"2020","journal-title":"Mol Ther Nucleic Acids"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/27.3.341","article-title":"Myocardial fibrosis: functional significance and regulatory factors","volume":"27","author":"Weber","year":"1993","journal-title":"Cardiovasc Res"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfr485","article-title":"Circulating microRNA expression is reduced in chronic kidney disease","volume":"26","author":"Neal","year":"2011","journal-title":"Nephrol Dialysis Transplant"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.120.14703","article-title":"Fibroblast growth factor 23 and blood pressure in older adults","volume":"76","author":"Drew","year":"2020","journal-title":"Hypertension"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2013.332","article-title":"Fibroblast growth factor 23 accelerates phosphate-induced vascular calcification in the absence of Klotho deficiency","volume":"85","author":"Jimbo","year":"2014","journal-title":"Kidney Int"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200304000-00027","article-title":"Mechanical function of the left atrium","volume":"98","author":"Pagel","year":"2003","journal-title":"Anesthesiology"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2019.01.059","article-title":"Left atrial structure and function, and left ventricular diastolic dysfunction: JACC state-of-the-art review","volume":"73","author":"Thomas","year":"2019","journal-title":"J Am Coll Cardiol"}],"container-title":["Frontiers in Nephrology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneph.2024.1455036\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T06:52:36Z","timestamp":1741243956000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneph.2024.1455036\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,6]]},"references-count":46,"alternative-id":["10.3389\/fneph.2024.1455036"],"URL":"https:\/\/doi.org\/10.3389\/fneph.2024.1455036","relation":{},"ISSN":["2813-0626"],"issn-type":[{"value":"2813-0626","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,6]]},"article-number":"1455036"}}