<scp>FGF</scp>‐23 is associated with cardiac troponin <scp>T</scp> and mortality in hemodialysis patients

Holden, Rachel M.; Beseau, David; Booth, Sarah L.; Adams, Michael; Garland, Jocelyn S.; Morton, Ross; Collier, Christopher M.; Foley, Robert N.

doi:10.1111/j.1542-4758.2011.00630.x

Cited by 25 publications

(12 citation statements)

References 25 publications

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“…This accumulation of serum phosphate then elevates serum FGF23, which at high concentrations may promote cardiac dysfunction. This cycle appears to continue in CKD since increased ANP/BNP and FGF23 are predictive of CKD progression (10,45) and cardiac pathologies (15,21,22,26,35,43,52).…”

Section: Discussionmentioning

confidence: 99%

FGF23 is a novel regulator of intracellular calcium and cardiac contractility in addition to cardiac hypertrophy

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Tchikrizov

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

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Recent observational studies in humans suggest that circulating FGF23 is independently associated with cardiac hypertrophy and increased mortality, but it is unknown whether FGF23 can directly alter cardiac function. We found that FGF23 significantly increased cardiomyocyte cell size in vitro, the expression of gene markers of cardiac hypertrophy, and total protein content of cardiac muscle. In addition, FGFR1 and FGFR3 mRNA were the most abundantly expressed FGF receptors in cardiomyocytes, and the coreceptor ␣-klotho was expressed at very low levels. We tested an animal model of chronic kidney disease (Col4a3 Ϫ/Ϫ mice) that has elevated serum FGF23. We found elevations in common hypertrophy gene markers in Col4a3 Ϫ/Ϫ hearts compared with wild type but did not observe changes in wall thickness or cell size by week 10. However, the Col4a3 Ϫ/Ϫ hearts did show reduced fractional shortening (Ϫ17%) and ejection fraction (Ϫ11%). Acute exposure of primary cardiomyocytes to FGF23 resulted in elevated intracellular Ca 2ϩ ([Ca 2ϩ ]i; F/Fo ϩ 86%) which was blocked by verapamil pretreatment. FGF23 also increased ventricular muscle strip contractility (67%), which was inhibited by FGF receptor antagonism. We hypothesize that although FGF23 can acutely increase [Ca 2ϩ ]i, chronically this may lead to decreases in contractile function or stimulate cardiac hypertrophy, as observed with other stress hormones. In conclusion, FGF23 is a novel bone/heart endocrine factor and may be an important mediator of cardiac Ca 2ϩ regulation and contractile function during chronic kidney disease. fibroblast growth factor 23; pathological cardiac hypertrophy; chronic kidney disease; Col4a3; cardiac function; ␣-klotho FIBROBLAST GROWTH FACTOR 23 (FGF23) is a hormone released primarily by osteocytes (2, 4, 14, 38) that functions to regulate phosphate and vitamin D homeostasis through direct actions on the kidney and parathyroid (2). Although an endocrine axis has been established between bone and kidney, a new paradigm is emerging in which FGF23 could be important in establishing an endocrine axis between bone and heart. Circulating levels of FGF23 are markedly elevated 100-to 1,000-fold in patients with chronic kidney disease (CKD) (24, 31) and are independently associated with cardiovascular morbidity and mortality (8,22,26,34,35,48,52). Specifically, an association between left ventricular (LV) hypertrophy and serum FGF23 levels has been established in CKD patients (20,36,52).Nevertheless, despite strong associations between FGF23 and adverse outcomes, it remains relatively unknown whether FGF23 is simply a marker of cardiac disease risk or a direct mediator of cardiac pathology and cardiac performance. Only one study to date has analyzed the direct effects of FGF23 on the heart both in vitro and in vivo (13). This important work by Faul et al. (13) shows that FGF23 can directly induce hypertrophy in isolated neonatal cardiomyocytes as well as with intramyocardial FGF23 injections. These authors also demonstrated that a FGF receptor (FGF...

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Section: Discussionmentioning

confidence: 99%

FGF23 is a novel regulator of intracellular calcium and cardiac contractility in addition to cardiac hypertrophy

Touchberry

Green

Tchikrizov

et al. 2013

American Journal of Physiology-Endocrinology and Metabolism

166

155

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“…Because the small sample and short follow-up may decrease the study quality, we excluded 6 studies among which sample sizes were less than 200 and duration of followup was less than one year [6][7][8][9][10][11]. Nevertheless, the inclusion of these studies still did not materially alter the overall combined risk estimate.…”

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confidence: 94%

FGF 23 and risk of all-cause mortality and cardiovascular events: A meta-analysis of prospective cohort studies

Xiao¹,

Luo²,

Huang³

et al. 2014

International Journal of Cardiology

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“…Kuro-o et al have shown mutated klotho gene to cause a syndrome resembling human ageing, including a short lifespan, infertility, arteriosclerosis, skin atrophy, osteoporosis and emphysema [16]. Holden et al ., studying patients with chronic kidney disease, have shown troponin T to be associated with FGF-23 [17]. In patients with chronic renal failure, serum FGF-23 concentrations were correlated with serum phosphate concentrations [18].…”

Section: Discussionmentioning

confidence: 99%

Troponin I, but not BNP, is Associated with Phosphorus, Calcium and Vitamin D in Stable Coronary Artery Disease

Nunes

2013

Kidney Blood Press Res

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Background: Elevated plasma cardiac troponin, elevated plasma phosphorus and decreased plasma vitamin D have been shown to be associated with negative outcomes. Methods and results: Troponin I, calcium, phosphorus and 25-OH vitamin D were studied in a cohort of 60 patients with stable coronary heart disease and preserved left ventricular function. Using a cut-off value of 0.012 ng/mL for plasma troponin I, patients with higher values (18 patients), when compared to the other patients (n=42), had higher mean values for plasma phosphorus (3.42+0.45 mg/dL vs 3.17+0.45 mg/dL, p= 0.041) and calcium (5.08+0.23 mEq/L vs 4.92+0.18 mEq/L, p= 0.016) and lower values for 25-OH vitamin D (14.2+5.6 ng/mL vs 19.4+8.8 ng/mL, p= 0.032). Binary logistic regression analysis showed that troponin I > 0.012 ng/ml is associated with increased phosphorus, increased calcium and decreased 25-OH vitamin D concentrations. A similar analysis using BNP >100 pg/mL failed to show signifcant associations with phosphorus, calcium and 25-OH vitamin D concentrations. Conclusions: In patients with stable coronary artery disease and preserved left ventricular function, those having cardiac troponin I > 0.012 ng/ml, but not those having BNP >100 pg/mL, had higher plasma phosphorus, higher plasma calcium and lower plasma 25-OH vitamin D concentrations than those having cardiac troponin I ≤ 0.012 ng/ml (or BNP ≤ 100 pg/mL).

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FGF‐23 is associated with cardiac troponin T and mortality in hemodialysis patients

Cited by 25 publications

References 25 publications

FGF23 is a novel regulator of intracellular calcium and cardiac contractility in addition to cardiac hypertrophy

FGF23 is a novel regulator of intracellular calcium and cardiac contractility in addition to cardiac hypertrophy

FGF 23 and risk of all-cause mortality and cardiovascular events: A meta-analysis of prospective cohort studies

Troponin I, but not BNP, is Associated with Phosphorus, Calcium and Vitamin D in Stable Coronary Artery Disease

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