{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:50:17Z","timestamp":1753890617729,"version":"3.41.2"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,6,29]],"date-time":"2023-06-29T00:00:00Z","timestamp":1687996800000},"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. Cardiovasc. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Chronic kidney disease (CKD) causes congestive heart failure (CHF) with systolic dysfunction and left ventricular hypertrophy (LVH), which is a major contributor to increased mortality in CKD patients. It remains unclear whether cardiovascular changes that occur during the course of CKD can be reversed when renal function is restored by transplantation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>To investigate this, chronic kidney disease was established in F344 rats by subtotal nephrectomy (SNx) for 8 weeks, followed by transplantation of a functional kidney from an isogenic F344 donor. SNx rats without transplantation and sham-operated animals served as controls. Renal function was assessed before and throughout the experiment. In addition, cardiac ultrasound was performed at weeks 0, 8, 12 and 16. At the end of the experiment, intra-arterial blood pressure was measured and kidneys and hearts were histologically and molecularly examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eight weeks after SNx, rats developed marked renal dysfunction associated with significant glomerulosclerosis and tubulointerstitial fibrosis, but also an increase in left ventricular mass. After transplantation, renal function normalized but relative heart weight and ventricular mass as assessed by ultrasound scans showed no reduction compared with SNx controls. However, left ventricular wall thickness, fractional shortening and ejection fraction was normalized by renal transplantation. At 8 weeks after kidney transplantation, cardiac expression of BNP and FGF23 was also at levels comparable to healthy controls, whereas these factors were significantly increased in SNx rats. Cardiac fibrosis, as measured by fibronectin mRNA expression, was completely normalized, whereas cardiac fibronectin protein was still slightly but not significantly increased in transplanted animals compared to controls. In addition, the myofibroblast marker collagen 1, as assessed by immunohistochemistry, was significantly increased in SNx rats and also normalized by renal transplantation. Interestingly, CD68+ macrophages were significantly reduced in the hearts of SNx rats and in transplanted animals at slightly higher levels compared to controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Restoration of renal function by kidney transplantation normalized early cardiac changes at most functional and molecular levels, but did not completely reverse LVH. However, further studies are needed to determine whether restoration of renal function can also reverse LVH at a later time point.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcvm.2023.1200323","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:23:22Z","timestamp":1688084602000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Experimental renal transplantation in rats improves cardiac dysfunction caused by chronic kidney disease while LVH persists"],"prefix":"10.3389","volume":"10","author":[{"given":"Linda","family":"Hagmayer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Mayer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadja","family":"Ebert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerstin","family":"Amann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christoph","family":"Daniel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,6,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1161\/circulationaha.120.050686","article-title":"Cardiovascular disease in chronic kidney disease: pathophysiological insights and therapeutic options","volume":"143","author":"Jankowski","year":"2021","journal-title":"Circulation"},{"key":"B2","first-page":"281","article-title":"Cardiovascular disease in patients with chronic kidney disease. A clinical review","volume":"59","author":"Kaisar","year":"2007","journal-title":"Minerva Urol Nefrol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"S112","DOI":"10.1053\/ajkd.1998.v32.pm9820470","article-title":"Clinical epidemiology of cardiovascular disease in chronic renal disease","volume":"32","author":"Foley","year":"1998","journal-title":"Am J Kidney Dis"},{"key":"B4","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1177\/039139880102401004","article-title":"Uremic toxicity: present state of the art","volume":"24","author":"Vanholder","year":"2001","journal-title":"Int J Artif Organs"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1093\/eurheartj\/ehp185","article-title":"The current status of interventions aiming at reducing sudden cardiac death in dialysis patients","volume":"30","author":"de Bie","year":"2009","journal-title":"Eur Heart J"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1018","DOI":"10.1681\/asn.V961018","article-title":"Myocyte\/capillary mismatch in the heart of uremic patients","volume":"9","author":"Amann","year":"1998","journal-title":"J Am Soc Nephrol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"1530","DOI":"10.1097\/01.asn.0000130154.42061.c6","article-title":"Increased infarct size in uremic rats: reduced ischemia tolerance?","volume":"15","author":"Dikow","year":"2004","journal-title":"J Am Soc Nephrol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2154","DOI":"10.1161\/01.Cir.0000095676.90936.80","article-title":"Kidney disease as a risk factor for development of cardiovascular disease: a statement from the American heart association councils on kidney in cardiovascular disease, high blood pressure research, clinical cardiology, and epidemiology and prevention","volume":"108","author":"Sarnak","year":"2003","journal-title":"Circulation"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1016\/j.cmet.2015.09.002","article-title":"Activation of cardiac fibroblast growth factor receptor 4 causes left ventricular hypertrophy","volume":"22","author":"Grabner","year":"2015","journal-title":"Cell Metab"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1","DOI":"10.14800\/ics.279","article-title":"Chronic sustained inflammation links to left ventricular hypertrophy and aortic valve sclerosis: a new link between S100\/RAGE and FGF23","volume":"1","author":"Yan","year":"2014","journal-title":"Inflamm Cell Signal"},{"key":"B11","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1186\/s12968-018-0504-5","article-title":"Cardiovascular magnetic resonance left ventricular strain in end-stage renal disease patients after kidney transplantation","volume":"20","author":"Gong","year":"2018","journal-title":"J Cardiovasc Magn Reson"},{"key":"B12","doi-asserted-by":"publisher","first-page":"e13558","DOI":"10.1111\/petr.13558","article-title":"Changes in cardiac function after renal transplantation in children: significance of pre-transplantation left ventricular hypertrophy","volume":"23","author":"Masuda","year":"2019","journal-title":"Pediatr Transplant"},{"key":"B13","doi-asserted-by":"publisher","first-page":"e13242","DOI":"10.1111\/ctr.13242","article-title":"Electrocardiographic changes before and after successful kidney transplantation and associations with cardiovascular and mortality outcomes","volume":"32","author":"Paajanen","year":"2018","journal-title":"Clin Transplant"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.4103\/1319-2442.301165","article-title":"Changes in left ventricular mass and cardiovascular risk factors after kidney transplantation","volume":"31","author":"Sreedharan","year":"2020","journal-title":"Saudi J Kidney Dis Transpl"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1807","DOI":"10.2215\/cjn.01400308","article-title":"Renal transplantation is not associated with regression of left ventricular hypertrophy: a magnetic resonance study","volume":"3","author":"Patel","year":"2008","journal-title":"Clin J Am Soc Nephrol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1034\/j.1399-3046.2001.005004279.x","article-title":"Changes in left ventricular mass index in children and adolescents after renal transplantation","volume":"5","author":"Mitsnefes","year":"2001","journal-title":"Pediatr Transplant"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1079","DOI":"10.1038\/ki.1992.390","article-title":"Reduced capillary density in the myocardium of uremic rats\u2014a stereological study","volume":"42","author":"Amann","year":"1992","journal-title":"Kidney Int"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e3000410","DOI":"10.1371\/journal.pbio.3000410","article-title":"The ARRIVE guidelines 2.0: updated guidelines for reporting animal research","volume":"18","author":"Percie du Sert","year":"2020","journal-title":"PLoS Biol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"969","DOI":"10.1097\/00004872-199309000-00011","article-title":"The effect of enalapril on glomerular growth and glomerular lesions after subtotal nephrectomy in the rat: a stereological analysis","volume":"11","author":"Amann","year":"1993","journal-title":"J Hypertens"},{"key":"B20","doi-asserted-by":"publisher","first-page":"e47","DOI":"10.1159\/000334955","article-title":"The proteasome inhibitor bortezomib prevents lupus nephritis in the NZB\/W F1 mouse model by preservation of glomerular and tubulointerstitial architecture","volume":"120","author":"Hainz","year":"2012","journal-title":"Nephron Exp Nephrol"},{"key":"B21","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1159\/000450559","article-title":"Improved left ventricular structure and function after successful kidney transplantation","volume":"41","author":"Hewing","year":"2016","journal-title":"Kidney Blood Press Res"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e13066","DOI":"10.1111\/petr.13066","article-title":"Hypertension and improved left ventricular mass index in children after renal transplantation","volume":"21","author":"Ramo\u011flu","year":"2017","journal-title":"Pediatr Transplant"},{"key":"B23","doi-asserted-by":"publisher","first-page":"64649","DOI":"10.18632\/oncotarget.11623","article-title":"FGF23 promotes myocardial fibrosis in mice through activation of beta-catenin","volume":"7","author":"Hao","year":"2016","journal-title":"Oncotarget"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1993","DOI":"10.1038\/s41598-017-02068-6","article-title":"FGF23\/FGFR4-mediated Left ventricular hypertrophy is reversible","volume":"7","author":"Grabner","year":"2017","journal-title":"Sci Rep"},{"key":"B25","doi-asserted-by":"publisher","first-page":"161","DOI":"10.3390\/toxins12030161","article-title":"Cardiac remodeling in chronic kidney disease","volume":"12","author":"Kaesler","year":"2020","journal-title":"Toxins (Basel)"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.1681\/asn.2014050465","article-title":"Klotho and phosphate are modulators of pathologic uremic cardiac remodeling","volume":"26","author":"Hu","year":"2015","journal-title":"J Am Soc Nephrol"},{"key":"B27","doi-asserted-by":"publisher","first-page":"e0124772","DOI":"10.1371\/journal.pone.0124772","article-title":"Association between inflammation and cardiac geometry in chronic kidney disease: findings from the CRIC study","volume":"10","author":"Gupta","year":"2015","journal-title":"PLoS One"},{"key":"B28","doi-asserted-by":"publisher","first-page":"F654","DOI":"10.1152\/ajprenal.00396.2021","article-title":"Interleukin-6 blockade reduces salt-induced cardiac inflammation and fibrosis in subtotal nephrectomized mice","volume":"323","author":"Tanaka","year":"2022","journal-title":"Am J Physiol Renal Physiol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"381","DOI":"10.1016\/j.ijcard.2015.10.126","article-title":"Macrophages dictate the progression and manifestation of hypertensive heart disease","volume":"203","author":"Kain","year":"2016","journal-title":"Int J Cardiol"},{"key":"B30","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.3390\/cells11071249","article-title":"Early protective role of inflammation in cardiac remodeling and heart failure: focus on TNF\u03b1 and resident macrophages","volume":"11","author":"Besse","year":"2022","journal-title":"Cells"},{"key":"B31","doi-asserted-by":"publisher","first-page":"2112","DOI":"10.1681\/asn.2006030204","article-title":"Cross-talk between the kidney and the cardiovascular system","volume":"17","author":"Amann","year":"2006","journal-title":"J Am Soc Nephrol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1016\/j.ejim.2010.07.001","article-title":"Circulating levels of asymmetric dimethylarginine are an independent risk factor for left ventricular hypertrophy and predict cardiovascular events in pre-dialysis patients with chronic kidney disease","volume":"21","author":"Shi","year":"2010","journal-title":"Eur J Intern Med"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1524","DOI":"10.1046\/j.1523-1755.2002.00600.x","article-title":"The elephant in uremia: oxidant stress as a unifying concept of cardiovascular disease in uremia","volume":"62","author":"Himmelfarb","year":"2002","journal-title":"Kidney Int"}],"container-title":["Frontiers in Cardiovascular Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2023.1200323\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:23:25Z","timestamp":1688084605000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcvm.2023.1200323\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,29]]},"references-count":33,"alternative-id":["10.3389\/fcvm.2023.1200323"],"URL":"https:\/\/doi.org\/10.3389\/fcvm.2023.1200323","relation":{},"ISSN":["2297-055X"],"issn-type":[{"type":"electronic","value":"2297-055X"}],"subject":[],"published":{"date-parts":[[2023,6,29]]},"article-number":"1200323"}}