Association between Circulating Fibroblast Growth Factor 23, α-Klotho, and the Left Ventricular Ejection Fraction and Left Ventricular Mass in Cardiology Inpatients

Shibata, Kensaku; Fujita, Shuichi; Morita, Hideaki; Okamoto, Yasumasa; Sohmiya, Koichi; Hoshiga, Masaaki; Ishizaka, Nobukazu

doi:10.1371/journal.pone.0073184

Cited by 53 publications

(52 citation statements)

References 48 publications

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“…Circulating and renal Klotho deficiency precedes the increase in plasma FGF23 25,60 and is a potential mechanism of stimulating FGF23. 17,36 The role of FGF23 in mediation of cardiac hypertrophy was suggested by epidemiologic data 30,[61][62][63] and strongly suggested by an animal study. 30 There may be interactive effects between FGF23 and Klotho.…”

Section: Discussionmentioning

confidence: 96%

Klotho and Phosphate Are Modulators of Pathologic Uremic Cardiac Remodeling

Hu¹,

Shi²,

Cho³

et al. 2015

Journal of the American Society of Nephrology

235

300

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Cardiac dysfunction in CKD is characterized by aberrant cardiac remodeling with hypertrophy and fibrosis. CKD is a state of severe systemic Klotho deficiency, and restoration of Klotho attenuates vascular calcification associated with CKD. We examined the role of Klotho in cardiac remodeling in models of Klotho deficiencygenetic Klotho hypomorphism, high dietary phosphate intake, aging, and CKD. Klotho-deficient mice exhibited cardiac dysfunction and hypertrophy before 12 weeks of age followed by fibrosis. In wild-type mice, the induction of CKD led to severe cardiovascular changes not observed in control mice. Notably, non-CKD mice fed a high-phosphate diet had lower Klotho levels and greatly accelerated cardiac remodeling associated with normal aging compared with those on a normal diet. Chronic elevation of circulating Klotho because of global overexpression alleviated the cardiac remodeling induced by either high-phosphate diet or CKD. Regardless of the cause of Klotho deficiency, the extent of cardiac hypertrophy and fibrosis correlated tightly with plasma phosphate concentration and inversely with plasma Klotho concentration, even when adjusted for all other covariables. High-fibroblast growth factor-23 concentration positively correlated with cardiac remodeling in a Klotho-deficient state but not a Klotho-replete state. In vitro, Klotho inhibited TGF-b1-, angiotensin II-, or high phosphate-induced fibrosis and abolished TGF-b1-or angiotensin II-induced hypertrophy of cardiomyocytes. In conclusion, Klotho deficiency is a novel intermediate mediator of pathologic cardiac remodeling, and fibroblast growth factor-23 may contribute to cardiac remodeling in concert with Klotho deficiency in CKD, phosphotoxicity, and aging.

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Section: Discussionmentioning

confidence: 96%

Klotho and Phosphate Are Modulators of Pathologic Uremic Cardiac Remodeling

Hu¹,

Shi²,

Cho³

et al. 2015

Journal of the American Society of Nephrology

235

300

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“…[10,11,15] It has been shown that FGF23 concentrations are elevated in patients who are on dialysis; [10][11][12] , however whether there is an association between FGF23 levels and LVH and other echocardiographic indexes of LV dysfunction in patients who are on dialysis is still unproven. [13,14,16] Therefore, in this study, we decided to evaluate the role of FGF23 on LVH, left ventricular mass index (LVMI), and other echocardiographic findings in a group of patients on hemodialysis without known CVD.…”

Section: Introductionmentioning

confidence: 99%

Association of serum intact fibroblast growth factor 23 with left ventricular mass and different echocardiographic findings in patients on hemodialysis

Nassiri

Hakemi

Safar-Pour

et al. 2016

Journal of Translational Internal Medicine

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Objectives: To determine the association of fibroblast growth factor 23 (FGF23) with left ventricular hypertrophy (LVH) through the assessment of left ventricular (LV) mass and left ventricular mass index (LVMI) in patients on hemodialysis, this study was done. Methods: All patients on hemodialysis who are older than 18 years and in whom hemodialysis vintage was at least 6 months were enrolled. All patients were on hemodialysis thrice a week for 4 h using low-flux dialysis filters, polysulfone membranes, reverse osmosis purified water, and bicarbonate-base hemodialysis solution. The exclusion criteria were any respiratory illness or pulmonary infection, cigarette smoking, and the presence of pericarditis or pericardial effusion. Additionally, patients with a known coronary artery disease, any form of cardiac arrhythmias, any cardiomyopathy or severe valvular heart disease diagnosed by echocardiography, acute congestive heart failure (CHF), and acute myocardial infarction were not included. Echocardiography was conducted by an experienced operator for all the enrolled patients using the ACUSON SC2000™ ultrasound system transducer (Siemens), with a frequency bandwidth of: 1.5-3.5 MHz. Patients were considered to have LVH if the LVMI was greater than 134 g/m 2 for men and greater than 110 g/m 2 for women. Results: A total of 61 patients (19 female and 42 male) were enrolled to the study. Mean (± SD) age of the patients was 59.6 ± 13.1 years. The median duration of hemodialysis was 23 (range: 6-120) months. The median predialysis level of FGF23 was 1,977 pg/mL (range: 155-8,870). LVH was seen in 73.8% of the patients (n = 45) and of them 66.7% were male. There was a statistically significant direct correlation between FGF23 and left ventricle diameter in end systole (LVDs) (r = 0.29, P = 0.027). However, the association of FGF23 with LV mass, LVMI, and left ventricular ejection fraction (LVEF) was not significant. Conclusion: This study does not show the correlation between FGF23 and LV mass in stable hemodialysis patients.

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“…FGF23 levels are found to be increased in the early stages of chronic kidney disease (CKD) 4,5) . The finding that FGF23 levels are associated with cardiac hypertrophy and dysfunction 6,7) suggests that FGF23 represents an independent risk factor for global or cardiac morbidity/ mortality 8,9) . It has been reported that coronary artery calcification (CAC) can be used as a surrogate marker of the total burden of coronary atherosclerosis and that the presence of CAC is associated with peripheral isch-"serum albumin"), and designated as corrected calcium (cCa).…”

Section: Introductionmentioning

confidence: 99%

“…It has been reported that coronary artery calcification (CAC) can be used as a surrogate marker of the total burden of coronary atherosclerosis and that the presence of CAC is associated with peripheral isch-"serum albumin"), and designated as corrected calcium (cCa). The measurement of FGF23 and -Klotho was performed using enzyme immunoassay kits as described elsewhere 7,24) . The eGFR was calculated by the following Modification of Diet in Renal Disease equation modified for Japanese subjects: eGFR 194 (serum creatinine) 1.094 (age) 0.…”

Section: Introductionmentioning

confidence: 99%

Gender Specific Association between Serum Fibroblast Growth Factor 23/α-Klotho and Coronary Artery and Aortic Valve Calcification

Morita

Takeda

Fujita

et al. 2015

J Atheroscler Thromb

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Aim: Fibroblast growth factor 23 (FGF23) and -Klotho have been recently identified to play a crucial role in calcium/phosphate metabolism. We herein investigated the possible relation between serum FGF23/ -Klotho levels and coronary artery calcification (CAC) and aortic valve calcification (AVC). Methods: Among subjects with diagnosed or suspected coronary artery disease (CAD), CAC and AVC were estimated via the Agatston score of 320-detector computed tomography images, and serum FGF23 and -Klotho levels were measured. Results: In total, 157 subjects were enrolled (75 women and 82 men). We performed logistic regression using CAC as a dependent variable; the highest FGF23 tertile ( 52.5 pg/mL) was significantly positively associated with CAC with an odds ratio of 6.61 versus the lowest FGF23 tertile ( 35.3 pg/mL) in women after the adjustment for potential confounding variables including age, renal function, hypertension, statin use, diuretic use, and calcium/phosphate metabolism related factors. In addition, the highest -Klotho tertile ( 561 pg/mL) was significantly associated with AVC with an odds ratio of 6.31 versus the lowest -Klotho tertile ( 306 pg/mL) in men after adjusting for the same variables. On the other hand, the association between FGF23 and CAC/AVC in men or that between -Klotho and CAC/AVC in women was nonsignificant. Conclusion: Among subjects with diagnosed or suspected CAD, serum FGF23 was positively associated with CAC in women and serum -Klotho was positively associated with AVC in men independent of the confounding variables, including the renal function and calcium/phosphate metabolismrelated factors. J Atheroscler Thromb, 2015; 22: 1338-1346.

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Association between Circulating Fibroblast Growth Factor 23, α-Klotho, and the Left Ventricular Ejection Fraction and Left Ventricular Mass in Cardiology Inpatients

Cited by 53 publications

References 48 publications

Klotho and Phosphate Are Modulators of Pathologic Uremic Cardiac Remodeling

Klotho and Phosphate Are Modulators of Pathologic Uremic Cardiac Remodeling

Association of serum intact fibroblast growth factor 23 with left ventricular mass and different echocardiographic findings in patients on hemodialysis

Gender Specific Association between Serum Fibroblast Growth Factor 23/α-Klotho and Coronary Artery and Aortic Valve Calcification

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