Please use this identifier to cite or link to this item: doi:10.22028/D291-39948
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Title: FGFR4 and Klotho Polymorphisms Are Not Associated with Cardiovascular Outcomes in Chronic Kidney Disease
Author(s): Sellier, Alexander B.
Seiler-Mußler, Sarah
Emrich, Insa E.
Böhm, Michael
Fliser, Danilo
Zawada, Adam M.
Heine, Gunnar H.
Language: English
Title: American Journal of Nephrology
Volume: 52
Issue: 10-11
Pages: 808-816
Publisher/Platform: Karger
Year of Publication: 2021
Free key words: Cardiovascular disease
Chronic kidney disease
Heart failure
Left-ventricular hypertrophy
Gene polymorphism
DDC notations: 610 Medicine and health
Publikation type: Journal Article
Abstract: Introduction: 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. Methods: The prospective Cardiovascular and Renal Outcome in CKD 2–4 Patients–The Fourth Homburg Evaluation study recruited CKD G2–G4 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 ± 2.1 years for the primary endpoints of cardiac decompensation and atherosclerotic cardiovascular disease (ASCVD). Results: Carriers of the different alleles did neither differ in baseline LVMI (rs351855: p = 0.861; rs9536314: p = 0.379) nor in LVMI changes between baseline and follow-up (rs351855: p = 0.181; rs9536314: p = 0.995). Hundred and four patients suffered cardiac decompensation, and 144 patients had ASCVD. Time to cardiac decompensation (rs351855: p = 0.316; rs9536314: p = 0.765) and ASCVD (p = 0.508 and p = 0.800, respectively) did not differ between carriers of different alleles. Discussion/Conclusion: 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.
DOI of the first publication: 10.1159/000519274
URL of the first publication:
Link to this record: urn:nbn:de:bsz:291--ds-399489
ISSN: 1421-9670
Date of registration: 12-Jun-2023
Description of the related object: Supplementary Material
Related object:
Faculty: M - Medizinische Fakultät
Department: M - Innere Medizin
Professorship: M - Prof. Dr. Michael Böhm
M - Prof. Dr. Danilo Fliser
Collections:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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