{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T21:56:51Z","timestamp":1768082211131,"version":"3.49.0"},"reference-count":44,"publisher":"S. Karger AG","issue":"10-11","license":[{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2021,1,1]],"date-time":"2021-01-01T00:00:00Z","timestamp":1609459200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am J Nephrol"],"published-print":{"date-parts":[[2021]]},"abstract":"<b><i>Introduction:<\/i><\/b> High plasma fibroblast growth factor 23 (FGF-23) predicts cardiovascular events in chronic kidney disease (CKD) patients. Experimental evidence suggests FGF receptor 4 (FGFR4) activation by FGF-23, and deficiency of the soluble form of its co-receptor Klotho promotes left-ventricular hypertrophy (LVH). To evaluate the clinical relevance of these findings, a Mendelian randomization study analyzed the association of genetic variants of FGFR4 and Klotho with echocardiographic parameters and cardiac events in CKD patients. <b><i>Methods:<\/i><\/b> The prospective Cardiovascular and Renal Outcome in CKD 2\u20134 Patients\u2013The Fourth Homburg Evaluation study recruited CKD G2\u2013G4 patients, of whom 519 consented to SNP genotyping (FGFR4: rs351855; Klotho: rs9536314). Echocardiographic examinations at baseline and 5 years later assessed prevalence of LVH by measurement of left-ventricular mass index (LVMI). Patients were followed for 5.1 \u00b1 2.1 years for the primary endpoints of cardiac decompensation and atherosclerotic cardiovascular disease (ASCVD). <b><i>Results:<\/i><\/b> Carriers of the different alleles did neither differ in baseline LVMI (rs351855: <i>p<\/i> = 0.861; rs9536314: <i>p<\/i> = 0.379) nor in LVMI changes between baseline and follow-up (rs351855: <i>p<\/i> = 0.181; rs9536314: <i>p<\/i> = 0.995). Hundred and four patients suffered cardiac decompensation, and 144 patients had ASCVD. Time to cardiac decompensation (rs351855: <i>p<\/i> = 0.316; rs9536314: <i>p<\/i> = 0.765) and ASCVD (<i>p<\/i> = 0.508 and <i>p<\/i> = 0.800, respectively) did not differ between carriers of different alleles. <b><i>Discussion\/Conclusion:<\/i><\/b> rs351855 and rs9536314 were not associated with LVMI or cardiac events. These findings do not provide evidence for a relevant clinical role of either FGFR4 stimulation or soluble form of Klotho deficiency in LVH development. <\/jats:p>","DOI":"10.1159\/000519274","type":"journal-article","created":{"date-parts":[[2021,10,21]],"date-time":"2021-10-21T21:01:16Z","timestamp":1634850076000},"page":"808-816","source":"Crossref","is-referenced-by-count":5,"title":["FGFR4 and Klotho Polymorphisms Are Not Associated with Cardiovascular Outcomes in Chronic Kidney Disease"],"prefix":"10.1159","volume":"52","author":[{"given":"Alexander B.","family":"Sellier","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Seiler-Mu\u00dfler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5048-3659","authenticated-orcid":false,"given":"Insa E.","family":"Emrich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"B\u00f6hm","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danilo","family":"Fliser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam M.","family":"Zawada","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunnar H.","family":"Heine","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"127","published-online":{"date-parts":[[2021,10,21]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1097\/01.asn.0000117977.14912.91"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1159\/000452880"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1172\/JCI46122"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.09.002"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014040325"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1593\/neo.08450"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.490052"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.022484299"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000157171.04054.30"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.08241109"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2010121224"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013050465"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfq309"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.2215\/CJN.07870713"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2009.05.013"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2005.04.031"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfu190"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.318556"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1038\/s41413-019-0051-1"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms2240"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.110.225888"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014050465"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1002\/emmm.201303716"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0044161"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12040"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1007\/s10741-011-9261-3"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1002\/jbmr.1923"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1097\/MNH.0000000000000232"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.1016\/j.kint.2018.02.018"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1016\/j.healun.2015.06.007"},{"key":"ref31","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-014-0713-8"},{"key":"ref32","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.113.000584"},{"key":"ref33","doi-asserted-by":"publisher","DOI":"10.1007\/s00467-015-3125-3"},{"key":"ref34","doi-asserted-by":"publisher","DOI":"10.1159\/000339026"},{"key":"ref35","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2012070719"},{"key":"ref36","doi-asserted-by":"publisher","DOI":"10.1080\/07435800.2016.1242604"},{"key":"ref37","doi-asserted-by":"publisher","DOI":"10.4274\/jcrpe.galenos.2021.2020.0287"},{"key":"ref38","doi-asserted-by":"publisher","DOI":"10.1038\/nature16449"},{"key":"ref39","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2369-15-197"},{"key":"ref40","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2015.08.017"},{"key":"ref41","doi-asserted-by":"publisher","DOI":"10.1093\/ndt\/gfu291"},{"key":"ref42","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.12710"},{"key":"ref43","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2011.01.012"},{"key":"ref44","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcmg.2012.06.003"}],"container-title":["American 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