Fibroblast growth factor 23 (FGF23) has been reported to induce left ventricular hypertrophy, but it remains unclear whether FGF23 plays a role in cardiac fibrosis. This study is attempted to investigate the role of FGF23 in post-infarct myocardial fibrosis in mice. We noted that myocardial and plasma FGF23 and FGF receptor 4 were increased in mice with heart failure as well as in cultured adult mouse cardiac fibroblasts (AMCFs) exposed to angiotensin II, phenylephrine, soluble fractalkine. Recombinant FGF23 protein increased active β-catenin , procollagen I and procollagen III expression in cultured AMCFs. Furthermore, intra-myocardial injection of adeno-associated virus-FGF23 in mice significantly increased left ventricular end-diastolic pressure and myocardial fibrosis, and markedly upregulated active β-catenin, transforming growth factor β (TGF-β), procollagen I and procollagen III in both myocardial infarction (MI) and ischemia/reperfusion (IR) mice, while β-catenin inhibitor or silencing of β-catenin antagonized the FGF23-promoted myocardial fibrosis in vitro and in vivo. These findings indicate that FGF23 promotes myocardial fibrosis and exacerbates diastolic dysfunction induced by MI or IR, which is associated with the upregulation of active β-catenin and TGF-β.

/pdf/fgf23-promotes-myocardial-fibrosis-in-mice-through-33csj2yi2y.pdf

FGF23 promotes myocardial fibrosis in mice through activation of β-catenin.

Chronic kidney disease-mineral bone disorder is frequent in patients with renal failure. It is characterized by abnormalities in mineral and bone metabolism with resulting hyperphosphatemia, low serum vitamin D, secondary hyperparathyroidism, altered bone morphology and strength, higher risk of bone fractures, and development of vascular or other soft tissue calcifications. Besides the recommendation to reduce phosphorus dietary intake, many drugs are currently available for the treatment of calcium/phosphate imbalance. Among them, phosphate binders represent a milestone. Calcium-based binders (calcium carbonate, calcium acetate) are effective in lowering serum phosphate, but their use has been associated with an increased risk of hypercalcemia and calcifications. Calcium-free binders (sevelamer hydrochloride, sevelamer carbonate, and lanthanum carbonate) are equally or slightly less effective than calcium-containing compounds. They would not induce an increase in calcium levels but may have relevant side effects, including gastrointestinal symptoms for sevelamer and risk of tissue accumulation for lanthanum. Accordingly, new phosphate binders are under investigation and some of them have already been approved. A promising option is sucroferric oxyhydroxide (Velphoro(®), PA21), an iron-based phosphate binder consisting of a mixture of polynuclear iron(III)-oxyhydroxide, sucrose, and starches. The present review is focused on pharmacology, mode of action, and pharmacokinetics of sucroferric oxyhydroxide, with a discussion on comparative efficacy, safety, and tolerability studies of this drug in chronic kidney disease and patient perspectives such as quality of life, satisfaction, and acceptability. Sucroferric oxyhydroxide has proven to be as effective as sevelamer in reducing phosphatemia with a similar safety profile and lower pill burden. Experimental and clinical studies have documented a minimal percentage of iron absorption without inducing toxicity. In conclusion, the overall benefit-risk balance of sucroferric oxyhydroxide is deemed to be positive, and this new drug may therefore represent a good alternative to traditional phosphate binders for the treatment of hyperphosphatemia in dialysis patients.

/pdf/phosphate-binders-for-the-treatment-of-chronic-kidney-2dhpvumwb4.pdf

Phosphate binders for the treatment of chronic kidney disease: role of iron oxyhydroxide.

Aims: This study aimed to assess whether neutrophil gelatinase-associated lipocalin (NGAL) and fibroblast growth factor 23 (FGF23) could be reliable biomarkers for early diagnosis of contrast-induced nephropathy (CIN).

Methods: 202 patients who underwent percutaneous coronary intervention (PCI) were included in the research. All subjects were divided into CIN group and non-CIN group. Serum NGAL and FGF23 were evaluated before and 0, 1, and 2 days after PCI. Serum levels of these two markers were compared intra-group and among groups. Receiver-operating characteristic (ROC) analysis and logistic regression models were conducted to assess the diagnostic performance of NGAL and FGF23 in detecting CIN.

Results: When compared with baseline values, serum levels of both NGAL and FGF23 in all subjects increased after PCI, and the values peaked 1 day after PCI, but the changing was greater in CIN group. There were obvious differences between two groups in serum NGAL after 1, 2 days, and similar differences present in serum FGF23 after 1 day. ROC analysis showed that the area under the curve (AUC) of relative values (percent change from the baseline) in NGAL after 1 day was 0.899 (95% CI: 0.834–0.964, p = .000), the optimum cutoff was 49% (sensitivity = 80%, specificity = 92.4%). And the AUC in FGF23 was 0.814 (95% CI: 0.733–0.894, p = .000), the optimum cutoff was 20% (sensitivity = 73.3%, specificity = 87.6%). Both serum NGAL and serum FGF23 could improve the clinical models in identifying CIN.

Conclusions: NGAL and FGF23 may have certain value in early diagnosis of CIN.

Serum NGAL and FGF23 may have certain value in early diagnosis of CIN

Assessment of blood level of fibroblast growth factor-23 (FGF-23) levels was done in forty patients with end-stage kidney disease (ESRD). We found that there were statistically significant positive correlations between FGF-23 and LVH, Phosphorus and Parathormone hormone. Statistically significant negative correlations were found between FGF-23 and corrected Calcium) and 25 (OH) vitamin D, but there was no significant correlation between FGF-23 and pulmonary artery systolic pressure. For prediction of FGF-23 Levels stepwise multiple linear regression analysis was done and revealed that the most 4 predictable values of FGF-23 are intact Parathormone hormone, corrected calcium, 25 (OH) vitamin D and SBP respectively. There were positive correlations between FGF-23 with LV mass and LV mass index. Statistically significant negative correlations were found between FGF-23 and LVIDs. A multiple discriminant functional analysis for prediction of LVH revealed that age, FGF-23, and Vitamin D are the most predictable variables. Hemodialysis patients with LVH had higher FGF-23 levels raising the possibility that FGF-23 may predict LVH.

https://www.longdom.org/open-access/fibroblast-growth-factor23-a-possible-cause-of-pulmonary-hypertension-andleft-ventricle-hypertrophy-in-hemodialysis-patients-2155-9880-1000449.pdf

Fibroblast Growth Factor-23: A Possible Cause of Pulmonary Hypertension andLeft Ventricle Hypertrophy in Hemodialysis Patients

Background In the past decade, fibroblast growth factor 23 (FGF23) has been recognized as an important biomarker of cardiovascular diseases. This study aimed to assess the relationship between FGF23 and the risk of cardiovascular diseases (CVDs) in general populations. Methods The protocol was registered prospectively in PROSPERO (CRD42021281837) and two authors independently searched for relevant studies in the PubMed, EMBASE, and Cochrane Library databases. The random effects model was applied. Results In total, 29 prospective studies involving 135,576 participants were included. In the general population, the category analysis revealed that elevated FGF23 levels were related to increased risks of myocardial infarction (MI) (RR: 1.40, 95%CI: 1.03−1.89), stroke (RR: 1.20, 95%CI: 1.02−1.43), heart failure (HF) (RR: 1.37, 95%CI: 1.23−1.52), CVD events (RR: 1.22, 95%CI: 0.99−1.51), cardiovascular mortality (RR: 1.46, 95%CI: 1.29−1.65), and all-cause mortality (RR: 1.50, 95%CI: 1.29−1.74). In the continuous analysis, per doubling of FGF23 was associated with increased risks of MI (RR: 1.08, 95%CI: 0.94−1.25), stroke (RR: 1.21, 95%CI: 0.99−1.48), HF (RR: 1.24, 95%CI: 1.14−1.35), CVD events (RR: 1.12, 95%CI: 0.99−1.27), cardiovascular mortality (RR: 1.43, 95%CI: 1.09−1.88), all-cause mortality (RR: 1.37, 95%CI: 1.15−1.62). Furthermore, the dose-response analysis demonstrated a potentially non-linear relationship between FGF23 and stroke, HF, and all-cause mortality. In contrast, a potentially linear relationship between FGF23 and cardiovascular mortality was observed (p for non-linearity = 0.73). Conclusion The present study suggests that increased serum FGF23 levels are positively related to CVD events and mortality in the general population. The clinical application of FGF23 levels to predict CVD risk requires further research.

/pdf/fibroblast-growth-factor-23-and-the-risk-of-cardiovascular-1qsg3qke.pdf

Fibroblast growth factor-23 and the risk of cardiovascular diseases and mortality in the general population: A systematic review and dose-response meta-analysis

The prevalence of chronic kidney disease (CKD) has now reached epidemic proportions and it is very likely that it will continue to rise with the increasing prevalence of juvenile diabetes mellitus, hypertension and aging population. CKD is a risk factor for cardiovascular disease (CVD) and cardiovascular disease can lead to CKD. It is also well known that patients with CKD have a higher risk of death from CVD than of progressing to end-stage renal disease that requires renal replacement therapy. In patients with CKD, there is a higher mortality from sudden cardiac death and congestive heart failure than coronary artery disease, which is not the case in the general population. The high prevalence of congestive heart failure in CKD is due to cardiac remodeling which progresses from concentric remodeling to concentric and eccentric hypertrophy, leading to left ventricular hypertrophy with both systolic and diastolic dysfunction. Recent studies have suggested that, in patients with chronic kidney disease, common traditional risk factors for cardiovascular disease such as hypertension, hyperlipidemia and obesity may not be the main determinants of cardiovascular disease. Among the various non-traditional cardiovascular risk factors present in patients with chronic kidney disease, abnormalities of CKD related mineral and bone disorder, which includes elevated fibroblast growth factor 23 (FGF23) have been one of the most extensively studied. However, after many years of research, the debate over the exact pathways by which FGF23 may lead to increased CVD still continues. FGF23 may have both direct and indirect effects on the cardiovascular system. Better understanding of the most relevant pathophysiologic pathways for FGF23 may lead to therapeutic interventions against cardiovascular disease in patients with CKD.

I. Ezumba

Papers

FGF23 and the heart

FGF23 e cuore