학술논문
FGFR4 and Klotho Polymorphisms Are Not Associated with Cardiovascular Outcomes in Chronic Kidney Disease
Document Type
Report
Author
Source
American Journal of Nephrology. December 1, 2021, Vol. 52 Issue 10-11, p808, 9 p.
Subject
Language
English
ISSN
0250-8095
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. Keywords: Cardiovascular disease, Chronic kidney disease, Heart failure, Left-ventricular hypertrophy, Gene polymorphism
Author(s): Alexander B. Sellier [a]; Sarah Seiler-Mußler [a,b]; Insa E. Emrich [c]; Michael Böhm [c]; Danilo Fliser [a]; Adam M. Zawada [a]; Gunnar H. Heine [a,d] Introduction Left-ventricular hypertrophy (LVH) [...]
Author(s): Alexander B. Sellier [a]; Sarah Seiler-Mußler [a,b]; Insa E. Emrich [c]; Michael Böhm [c]; Danilo Fliser [a]; Adam M. Zawada [a]; Gunnar H. Heine [a,d] Introduction Left-ventricular hypertrophy (LVH) [...]