FGF-23 and future cardiovascular events in patients with chronic kidney disease before initiation of dialysis treatment

Seiler, Sarah; Reichart, B; Röth, Daniel; Seibert, Eric; Fliser, Danilo; Heine, Gunnar H.

doi:10.1093/ndt/gfq309

Cited by 175 publications

(137 citation statements)

References 27 publications

Supporting

Mentioning

127

Contrasting

Unclassified

Order By: Relevance

“…If FGF23 is directly correlated to CV and coronary events (29,(45)(46)(47), vascular alterations (48), left ventricular hypertrophy (28,30), and mortality (9,49,50), it seems obvious that a VLpD may be useful to prevent CV events reducing FGF23 levels.…”

Section: Discussionmentioning

confidence: 99%

Acute Effects of Very-Low-Protein Diet on FGF23 Levels

Iorio¹,

Micco²,

Torraca³

et al. 2012

Clinical Journal of the American Society of Nephrology

104

View full text Add to dashboard Cite

SummaryBackground and objectives High levels of fibroblast growth factor 23 are associated with mortality, CKD progression, and calcification in CKD patients. The aim of this pilot study is to assess whether a very-low-protein diet (0.3 g/kg per day) with a consequent low intake of phosphorus would reduce fibroblast growth factor 23 compared with a low-protein diet (0.6 g/kg per day) in CKD patients not yet on dialysis.Design, setting, participants, & measurements A prospective, randomized, controlled crossover study was performed in which 32 patients were randomized into two groups. Group A (16 patients) received a very-lowprotein diet (0.3 g/kg body wt per day) supplemented with ketoanalogues during the first week and a lowprotein diet during the second week, and group B (16 patients) received a low-protein diet during the first week and a very-low-protein diet during the second week. Fibroblast growth factor 23, seric, and urinary phosphate levels were measured at baseline and the end of each study period.Results After only 1 week of the very-low-protein diet, reductions in fibroblast growth factor 23 levels (33.5%), serum phosphate (12%), and urinary phosphate (34%) with the very-low-protein diet compared with the lowprotein diet were observed. Serum and urinary phosphate levels and protein intake were significant determinants of fibroblast growth factor 23 (95% confidence interval=1.04-1.19, 1.12-1.37, and 1.51-2.23, respectively).Conclusions A very-low-protein diet supplemented with ketoanalogues reduced fibroblast growth factor 23 levels in CKD patients not yet on dialysis.

show abstract

Section: Discussionmentioning

confidence: 99%

Acute Effects of Very-Low-Protein Diet on FGF23 Levels

Iorio¹,

Micco²,

Torraca³

et al. 2012

Clinical Journal of the American Society of Nephrology

104

View full text Add to dashboard Cite

show abstract

“…It is assumed that the only source of circulating FGF23 in renal disease is the bone [21,31], in spite of the fact that FGF23 transcripts can be detected in liver, heart, ISSN:2155-9880 JCEC, an open access journal Heart Transplantation J Clin Exp Cardiolog brain and thymus. However, with the increasing number of publications demonstrating the involvement of FGF23 in left ventricular dysfunction [12], atrial fibrillation [12] and left ventricular hypertrophy [13] it appears feasible that under pathological conditions secondary sources of FGF23 exist. In order to determine whether cardiomyocytes are able to express FGF23 we stimulated cultures with a variety of growth factors and cytokines.…”

Section: Discussionmentioning

confidence: 99%

“…Impairment in renal function leads to a decreased phosphate excretion which is believed to be compensated through increases in circulating FGF23 by inducing phosphate excretion and negative regulation of vitamin D synthesis. Recent studies demonstrated the association of FGF23 with left ventricular dysfunction [12], atrial fibrillation [12], left ventricular hypertrophy [13] and it might serve as a prognostic marker for all-cause mortality and surviving in stable systolic HF [14,15]. A correlation between Chronic Kidney Disease (CKD) and HF is well recognized.…”

Section: Introductionmentioning

confidence: 99%

Oncostatin M Induces FGF23 Expression in Cardiomyocytes

Richter¹,

Polyakova²,

Gajawada³

2012

J Clin Exp Cardiolog

View full text Add to dashboard Cite

Background: It is well-known that elevated levels of Fibroblast Growth Factor-23 (FGF23), a bone derived hormone, in circulation are associated with renal failure. Recent studies emphasize the correlation between Heart Failure (HF) and FGF23, but the ability of cardiomyocytes themselves to express and secrete this phosphatonin is yet unknown. A further factor involved in HF is the cytokine oncostatin M (OSM). The aims of our study were: 1) to analyze the myocardium of HF patients in terms of FGF23 expression in cardiomyocytes and 2) to assess whether OSM is able to induce FGF23 production in cardiomyocytes. Methods:Cultures of adult cardiomyocytes were treated with OSM and screened for the expression of FGF23 transcripts. FGF23 secretion was determined by Western blot and ELISA of cell culture supernatants. Heart explants of HF patients with Dilated Cardiomyopathy (DCM), Ischemic Cardiomyopathy (ICM) and myocarditis (Myo) were analyzed by immunofluorescence using FGF23 antibodies and compared with healthy controls. FGF23 levels were also determined in mice with a cardiac restricted overexpression of Monocyte Chemotactic Protein-1 (MCP1), which developed an "inflammatory" Heart Failure (iHF) due to macrophage infiltration.Results: OSM massively induced the expression and secretion of FGF23 in cultured adult cardiomyocytes. Confocal microscopy revealed high amounts of FGF23 positive cardiomyocytes in the myocardium of patients with ischemic heart disease (IHD), myocarditis, dilated cardiomyopathy (DCM) and in mice with iHF. Conclusions:The presence of FGF23 in the myocardium of patients with different types of HF and in mice with "inflammatory" HF suggests that macrophages are responsible for the FGF23 expression in cardiomyocytes via OSM. Whether FGF23 acts as a regeneration promoting factor and/or potentially serves as a HF/transplantation marker has to be clarified.

show abstract

“…Epidemiologic and experimental data support FGF23 elevation as a novel risk factor for ESRD, cardiovascular disease, and mortality (2)(3)(4)(5). These findings, along with evidence that FGF23 levels increase with dietary phosphate loading and decrease with restriction (6)(7)(8), have stimulated interest in developing clinical strategies to reduce FGF23 levels in CKD.…”

Section: Introductionmentioning

confidence: 96%

Effects of Dietary Phosphate Restriction and Phosphate Binders on FGF23 Levels in CKD

Isakova

Barchi-Chung

Enfield

et al. 2013

Clinical Journal of the American Society of Nephrology

136

100

View full text Add to dashboard Cite

SummaryBackground Elevated levels of fibroblast growth factor 23 (FGF23) are associated with increased risk of adverse outcomes in patients with CKD. Reducing dietary phosphate intake or absorption may decrease FGF23 levels, but data on the combined effects of dietary phosphate restriction and phosphate binders in CKD are limited.Design, setting, participants, & measurements In this 232 factorial, single-blinded, placebo-controlled, 3-month study, conducted between July 2009 and March 2012, 39 patients with CKD stages 3 or 4 and normal serum phosphate levels were randomly assigned to one of four groups: ad libitum diet plus lanthanum carbonate (LC) placebo (n=10), 900-mg phosphate diet plus LC placebo (n=10), ad libitum diet plus LC (n=11), or 900-mg phosphate diet plus LC (n=8). The dose of LC was 1000 mg three times daily with meals. Dietary restriction was accomplished with outpatient counseling. The primary end point was change in FGF23 levels from baseline.Results Compared with ad libitum diet, the 900-mg phosphate diet did not significantly reduce FGF23 levels (diet 3 time interaction, P=0.05). Compared with placebo, LC alone also did not significantly reduce FGF23 levels (LC 3 time interaction, P=0.21). However, the dual intervention significantly decreased FGF23 levels throughout the study period (diet 3 LC 3 time interaction, P=0.02), resulting in a 35% (95% confidence interval, 8%-62%) reduction by study end. ConclusionThe combination of LC plus counseling for a phosphate-restricted diet decreased FGF23 levels in patients with CKD stages 324 and normal serum phosphate levels.

show abstract

FGF-23 and future cardiovascular events in patients with chronic kidney disease before initiation of dialysis treatment

Cited by 175 publications

References 27 publications

Acute Effects of Very-Low-Protein Diet on FGF23 Levels

Acute Effects of Very-Low-Protein Diet on FGF23 Levels

Oncostatin M Induces FGF23 Expression in Cardiomyocytes

Effects of Dietary Phosphate Restriction and Phosphate Binders on FGF23 Levels in CKD

Contact Info

Product

Resources

About