Fibroblast growth factor 23 is not associated with and does not induce arterial calcification

Elevated fibroblast growth factor 23 (FGF23) is associated with cardiovascular disease in patients with chronic kidney disease. As a potential mediating mechanism, FGF23 induces left ventricular hypertrophy; however, its role in arterial calcification is less clear. In order to study this we quantified coronary artery and thoracic aorta calcium by computed tomography in 1501 patients from the Chronic Renal Insufficiency Cohort (CRIC) study within a median of 376 days (interquartile range 331 to 420 days) of baseline. Baseline plasma FGF23 was not associated with prevalence or severity of coronary artery calcium after multivariable adjustment. In contrast, higher serum phosphate levels were associated with prevalence and severity of coronary artery calcium, even after adjustment for FGF23. Neither FGF23 nor serum phosphate were consistently associated with thoracic aorta calcium. We could not detect mRNA expression of FGF23 or its co-receptor, klotho, in human or mouse vascular smooth muscle cells, or normal or calcified mouse aorta. Whereas elevated phosphate concentrations induced calcification in vitro, FGF23 had no effect on phosphate uptake or phosphate-induced calcification regardless of phosphate concentration or even in the presence of soluble klotho. Thus, in contrast to serum phosphate, FGF23 is not associated with arterial calcification and does not promote calcification experimentally. Hence, phosphate and FGF23 promote cardiovascular disease through distinct mechanisms.

• Publication year

  2013

• Venue

  Kidney International

• Publication date

  2013-01-23

• Fields of study

  Medicine

• Identifiers
  DOI 10.1038/ki.2013.3PMID 23389416PMCID 3672330
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Expression of FGF23/KLOTHO system in human vascular tissue.

  2013cited by this paper
• Fibroblast Growth Factor 23 Induces Left Ventricular Hypertrophy

  2012cited by this paper
• Fibroblast growth factor-23 and death, heart failure, and cardiovascular events in community-living individuals: CHS (Cardiovascular Health Study).

  2012cited by this paper
• Vascular Klotho Deficiency Potentiates the Development of Human Artery Calcification and Mediates Resistance to Fibroblast Growth Factor 23

  2012cited by this paper
• Fibroblast growth factor 23 and the bone-vascular axis: lessons learned from animal studies.

  2012cited by this paper
• Soluble serum Klotho in diabetic nephropathy: relationship to VEGF-A.

  2012cited by this paper
• FGF23 is independently associated with vascular calcification but not bone mineral density in patients at various CKD stages

  2012cited by this paper
• Chronic kidney disease

  2012cited by this paper
• Serum level of the phosphaturic factor FGF23 is associated with abdominal aortic calcification in men: the STRAMBO study.

  2012cited by this paper
• FGF23 neutralization improves chronic kidney disease-associated hyperparathyroidism yet increases mortality.

  2012cited by this paper
• Estimating GFR among participants in the Chronic Renal Insufficiency Cohort (CRIC) Study.

  2012cited by this paper
• FGF23 induces left ventricular hypertrophy.

  2011cited by this paper
• Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease.

  2011cited by this paper
• Fibroblast growth factor 23, cardiovascular disease risk factors, and phosphorus intake in the health professionals follow-up study.

  2011cited by this paper
• Klotho deficiency causes vascular calcification in chronic kidney disease.

  2011cited by this paper
• Thoracic aortic calcification and coronary heart disease events: the multi-ethnic study of atherosclerosis (MESA).

  2011cited by this paper
• Relationship of estimated GFR and coronary artery calcification in the CRIC (Chronic Renal Insufficiency Cohort) Study.

  2011cited by this paper
• Elastin degradation and vascular smooth muscle cell phenotype change precede cell loss and arterial medial calcification in a uremic mouse model of chronic kidney disease.

  2011cited by this paper
• CKD in Hispanics: Baseline characteristics from the CRIC (Chronic Renal Insufficiency Cohort) and Hispanic-CRIC Studies.

  2011cited by this paper
• Correlates of osteoprotegerin and association with aortic pulse wave velocity in patients with chronic kidney disease.

  2011cited by this paper
• Peripheral artery calcifications evaluated by histology correlate to those detected by CT: relationships with fetuin-A and FGF-23.

  2011cited by this paper
• Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease.

  2011cited by this paper
• FGF-23 associates with death, cardiovascular events, and initiation of chronic dialysis.

  2011cited by this paper
• The role of FGF-23 in CKD-MBD and cardiovascular disease: friend or foe?

  2010cited by this paper
• FGF-23 and vascular dysfunction in patients with stage 3 and 4 chronic kidney disease.

  2010cited by this paper
• Statistical Modeling of Agatston Score in Multi-Ethnic Study of Atherosclerosis (MESA)

  2010cited by this paper
• Fibroblast growth factor-23 (FGF-23) is independently correlated to aortic calcification in haemodialysis patients.

  2010cited by this paper
• Forging forward with 10 burning questions on FGF23 in kidney disease.

  2010cited by this paper
• Decreased expression of klotho gene in uremic atherosclerosis in apolipoprotein E-deficient mice.

  2010cited by this paper
• The Associations of Fibroblast Growth Factor 23 and Uncarboxylated Matrix Gla Protein With Mortality in Coronary Artery Disease: The Heart and Soul Study

  2010cited by this paper
• Phosphate feeding induces arterial medial calcification in uremic mice: role of serum phosphorus, fibroblast growth factor-23, and osteopontin.

  2009cited by this paper
• Klotho ablation converts the biochemical and skeletal alterations in FGF23 (R176Q) transgenic mice to a Klotho-deficient phenotype.

  2009cited by this paper
• Association of serum phosphate with vascular and valvular calcification in moderate CKD.

  2009cited by this paper
• Fibroblast Growth Factor 23 and Left Ventricular Hypertrophy in Chronic Kidney Disease

  2009cited by this paper
• Chronic Renal Insufficiency Cohort (CRIC) Study: baseline characteristics and associations with kidney function.

  2009cited by this paper
• Fibroblast Growth Factor 23 and Mortality among Patients Undergoing Hemodialysis

  2009cited by this paper
• Relation between plasma fibroblast growth factor‐23, serum fetuin‐A levels and coronary artery calcification evaluated by multislice computed tomography in patients with normal kidney function

  2008cited by this paper
• Association of mild to moderate kidney dysfunction and coronary calcification.

  2008cited by this paper
• Fibroblast growth factor 23 and mortality among patients undergoing hemodialysis.

  2008cited by this paper
• Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease.

  2008cited by this paper
• Role of hyperphosphatemia and 1,25-dihydroxyvitamin D in vascular calcification and mortality in fibroblastic growth factor 23 null mice.

  2007cited by this paper
• Progressive vascular calcification over 2 years is associated with arterial stiffening and increased mortality in patients with stages 4 and 5 chronic kidney disease.

  2007cited by this paper
• Mortality effect of coronary calcification and phosphate binder choice in incident hemodialysis patients.

  2007cited by this paper
• BONE METABOLISM AND DISEASE IN CHRONIC KIDNEY DISEASE

  2007cited by this paper
• How fibroblast growth factor 23 works.

  2007cited by this paper
• Dietary phosphorus regulates serum fibroblast growth factor-23 concentrations in healthy men.

  2006cited by this paper
• Vascular calcification and cardiovascular function in chronic kidney disease.

  2006cited by this paper
• Role of the Sodium-Dependent Phosphate Cotransporter, Pit-1, in Vascular Smooth Muscle Cell Calcification

  2006cited by this paper
• Role of fibroblast growth factor-23 in peripheral vascular calcification in non-diabetic and diabetic hemodialysis patients

  2006cited by this paper
• Regulation of Fibroblast Growth Factor-23 Signaling by Klotho*

  2006cited by this paper
• Pretreatment serum FGF-23 levels predict the efficacy of calcitriol therapy in dialysis patients.

  2005cited by this paper
• FGF-23 transgenic mice demonstrate hypophosphatemic rickets with reduced expression of sodium phosphate cotransporter type IIa.

  2004cited by this paper
• Transgenic mice overexpressing human fibroblast growth factor 23 (R176Q) delineate a putative role for parathyroid hormone in renal phosphate wasting disorders.

  2004cited by this paper
• A modified poisson regression approach to prospective studies with binary data.

  2004cited by this paper
• Transgenic mice expressing fibroblast growth factor 23 under the control of the alpha1(I) collagen promoter exhibit growth retardation, osteomalacia, and disturbed phosphate homeostasis.

  2004cited by this paper
• Prevalence of chronic kidney disease and decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey.

  2003cited by this paper
• The Chronic Renal Insufficiency Cohort (CRIC) Study: Design and Methods.

  2003cited by this paper
• Human Fibroblast Growth Factor-23 Mutants Suppress Na+-dependent Phosphate Co-transport Activity and 1α,25-Dihydroxyvitamin D3 Production*

  2003cited by this paper
• K/DOQI clinical practice guidelines for bone metabolism and disease in chronic kidney disease.

  2003cited by this paper
• Phosphorus and uremic serum up-regulate osteopontin expression in vascular smooth muscle cells.

  2002cited by this paper
• Arterial Calcifications, Arterial Stiffness, and Cardiovascular Risk in End-Stage Renal Disease

  2001cited by this paper
• Coronary-artery calcification in young adults with end-stage renal disease who are undergoing dialysis.

  2000cited by this paper
• Phosphate regulation of vascular smooth muscle cell calcification.

  2000cited by this paper
• Mutation of the mouse klotho gene leads to a syndrome resembling ageing

  1997cited by this paper
• Vitamin C intake and susceptibility to pneumonia.

  1997cited by this paper
• Quantification of coronary artery calcium using ultrafast computed tomography.

  1990cited by this paper
• Fibroblast Growth Factor-23 (fgf-23) Is Independently Correlated to Aortic Calcification in Haemodialysis Patients Department of Endocrinology and Association of Fgf-23 with Aortic Calcification 2679

  year unknowncited by this paper

• High-Phosphate-Induced Hypertension: The Pathogenic Role of Fibroblast Growth Factor 23 (FGF23) Signaling in Sympathetic Nervous System Activation

  2026cites this paper
• The true cost of phosphate control in chronic kidney disease

  2025cites this paper
• FGF-23 and Long-term Outcome in Peripheral Artery Disease.

  2025cites this paper
• Femoral artery calcification predicts hip fracture in maintenance hemodialysis patients

  2025cites this paper
• Higher versus Lower Phosphate Targets for Patients Undergoing In-Center Hemodialysis: A Randomized Controlled Trial.

  2025cites this paper
• Hormonal and mineral dysregulation determines the dynamics of calcification in adenine-induced CKD in male rats.

  2025cites this paper
• Serum Hepcidin as a Biomarker of Subclinical Atherosclerosis in Peritoneal Dialysis: A Cross-Sectional Study

  2025cites this paper
• Serum calciprotein particle‐to‐phosphate ratio as a predictor of cardiovascular events in incident hemodialysis patients

  2024cites this paper
• Comparative Analysis of Vascular Calcification Risk Factors in Pre-Hemodialysis and Prevalent Hemodialysis Adult Patients: Insights into Calcification Biomarker Associations and Implications for Intervention Strategies in Chronic Kidney Disease

  2024cites this paper
• Non-Classical Effects of FGF23: Molecular and Clinical Features

  2024cites this paper
• Role of klotho and fibroblast growth factor 23 in arterial calcification, thickness, and stiffness: a meta-analysis of observational studies

  2024cites this paper
• Results of the EPISODE trial plead for reasonable practice-based serum phosphate lowering in patients on dialysis.

  2024cites this paper
• Targeting aging with the healthy skeletal system: The endocrine role of bone

  2023cites this paper
• Correlation of Serum FGF23 and Chronic Kidney Disease-Mineral and Bone Abnormality Markers With Cardiac Structure Changes in Maintenance Hemodialysis Patients

  2023cites this paper
• Vascular calcification: from the perspective of crosstalk

  2023cites this paper
• Association of serum 25-hydroxyvitamin D3, fibroblast growth factor-23, and C1q/tumor necrosis factor-related protein-3 with coronary artery calcification in nondialysis chronic kidney disease patients

  2023cites this paper
• Pathophysiology and Clinical Impacts of Chronic Kidney Disease on Coronary Artery Calcification

  2023cites this paper
• FGF23 and klotho at the intersection of kidney and cardiovascular disease

  2023cites this paper
• NT‐proBNP Mediates the Association Between FGF23 and All‐Cause Mortality in Individuals With Type 2 Diabetes

  2023cites this paper
• FGF23 AND ALTERED MINERAL HOMEOSTASIS IN KIDNEY DISEASE AND FOLLOWING INTRAVENOUS IRON.

  2023cites this paper
• The direct effect of fibroblast growth factor 23 on vascular smooth muscle cell phenotype and function

  2022cites this paper
• Parathyroid hormone levels and pulse wave velocity in hemodialysis patients

  2022cites this paper
• Prazosin improves neurogenic acute heart failure through downregulation of fibroblast growth factor 23 in rat hearts

  2022cites this paper
• Genetic Evidence for a Causal Role of Serum Phosphate in Coronary Artery Calcification: The Rotterdam Study

  2022cites this paper
• Fibroblast growth factor 23 and carotid intima media thickness in non-diabetic chronic kidney disease patients

  2022cites this paper
• Improvement of Mineral and Bone Disorders After Renal Transplantation

  2022cites this paper
• Assessment of the level of fibrosising factors in patients with coronary heart disease and chronic kidney disease

  2022cites this paper
• Fibroblast Growth Factor 23 as Regulator of Vitamin D Metabolism.

  2022cites this paper
• Phosphorus metabolism and fibroblast growth factor 23 in chronic kidney disease

  2022cites this paper
• Deoxycholic Acid and Coronary Artery Calcification in the Chronic Renal Insufficiency Cohort

  2022cites this paper
• Histone Lysine Methylation Modification and Its Role in Vascular Calcification

  2022cites this paper
• Klotho-independent actions of FGF23—targets, signal transduction, and cellular effects

  2021cites this paper
• The Importance of Phosphate Control in Chronic Kidney Disease

  2021cites this paper
• Reducing the burden of cardiovascular disease in children with chronic kidney disease: prevention vs. damage limitation

  2021cites this paper
• Effects of FGF23 in the distal nephron

  2021cites this paper
• FGF23 and heart and vascular disease

  2021cites this paper
• FGF23—resolved issues, remaining controversies, and future questions—a clinician's perspective

  2021cites this paper
• FGF23 and kidney disease

  2021cites this paper
• The experimental detection of FGF23 responsiveness in target organs

  2021cites this paper
• The role of AMP‐activated protein kinase α1‐mediated endoplasmic reticulum stress in alleviating the toxic effect of uremic toxin indoxyl sulfate on vascular endothelial cells by Klotho

  2021cites this paper
• Phosphate and fibroblast growth factor 23 in diabetes

  2021cites this paper
• Risk factors for abdominal aortic calcifications in chronic hemodialysis patients

  2021cites this paper
• High cut-off dialysis mitigates pro-calcific effects of plasma on vascular progenitor cells

  2021cites this paper
• Abstract 10670: Kidney Function, Bone-Mineral Metabolism Markers, and Calcification of Coronary Arteries, Aorta, and Cardiac Valves in Older Adults

  2021cites this paper
• Chronic kidney disease : a clinical model of premature vascular aging

  2021cites this paper
• Role of Glycosylation in Vascular Calcification

  2021cites this paper
• Higher Serum Phosphorus Is Not an Independent Risk Factor of Mortality in Heart Failure with Reduced Ejection Fraction

  2021cites this paper
• Chronic Kidney Disease – Mineral and Bone Disorder (CKD-MBD)

  2021cites this paper
• Role of Matrix Gla Protein in the Complex Network of Coronary Artery Disease: A Comprehensive Review

  2021cites this paper
• The Role of Bone Volume, FGF23 and Sclerostin in Calcifications and Mortality; a Cohort Study in CKD Stage 5 Patients

  2021cites this paper
• Understanding the Stony Bridge between Osteoporosis and Vascular Calcification: Impact of the FGF23/Klotho axis

  2021cites this paper
• A feline-focused review of chronic kidney disease-mineral and bone disorders - Part 1: Physiology of calcium handling.

  2021cites this paper
• Nutrition and Diet Therapy for DKD

  2020cites this paper
• Fibroblast Growth Factor 21 Predicts and Promotes Vascular Calcification in Haemodialysis Patients

  2020cites this paper
• Diabetic Kidney Disease

  2020cites this paper
• Iron Infusion and Induced Hypophosphatemia: The Role of Fibroblast Growth Factor‐23

  2020cites this paper
• Rare diseases of phosphate and calcium metabolism: crossing glances between nephrology and endocrinology.

  2020cites this paper
• Paricalcitol regulatory effect on inflammatory, fibrotic and anticalcificating parameters in renal patient. Far beyond mineral bone disease regulation

  2020cites this paper
• Targeting Vascular Calcification in Chronic Kidney Disease

  2020cites this paper
• Endocrine fibroblast growth factors as potential biomarkers for chronic kidney disease

  2020cites this paper
• Fibroblast Growth Factor 23 and Adverse Clinical Outcomes in Type 2 Diabetes: a Bitter-Sweet Symphony

  2020cites this paper
• Therapeutic options for chronic kidney disease-associated pulmonary hypertension.

  2020cites this paper
• Investigation of nicotinamide as more than an anti-phosphorus drug in chronic hemodialysis patients: a single-center, double-blind, randomized, placebo-controlled trial

  2020cites this paper
• New insights into the role of FGF-23 and Klotho in cardiovascular disease in chronic kidney disease patients.

  2020cites this paper
• Microcalcifications and plaque rupture

  2020cites this paper
• Intact Fibroblast Growth Factor 23 and Peripheral Vascular Complications in Patients on Hemodialysis

  2020cites this paper
• Calcification Biomarkers, Subclinical Vascular Disease, and Mortality Among Multiethnic Dialysis Patients

  2020cites this paper
• Research Models for Studying Vascular Calcification

  2020cites this paper
• Klotho/FGF23 and Wnt Signaling as Important Players in the Comorbidities Associated with Chronic Kidney Disease

  2020cites this paper
• Selected cardiovascular risk factors in early stages of chronic kidney disease

  2020cites this paper
• Hyperphosphatemia and Chronic Kidney Disease: A Major Daily Concern Both in Adults and in Children

  2020cites this paper
• Les inhibiteurs de la voie Wnt dans un modèle animal d'insuffisance rénale chronique avec calcification vasculaire

  2020cites this paper
• Vascular calcification relationship to vascular biomarkers and bone metabolism in advanced chronic kidney disease.

  2020cites this paper
• Fibroblast growth factor 23: are we ready to use it in clinical practice?

  2020cites this paper
• Paricalcitol regulatory effect on inflammatory, fibrotic and anticalcificating parameters in renal patiente. Far beyond mineral bone disease regulation.

  2019cites this paper
• Progress in Pathological Mechanism of Vascular Calcification in Patients with Chronic Kidney Disease

  2019influential citation
• Regulation and Effects of FGF23 in Chronic Kidney Disease.

  2019cites this paper
• Cardio-ankle vascular index is linked to deranged metabolic status, especially high HbA1c and monocyte-chemoattractant-1 protein, in predialysis chronic kidney disease

  2019cites this paper
• FGF23 and Phosphate–Cardiovascular Toxins in CKD

  2019cites this paper
• Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia

  2019cites this paper
• Vascular Calcification in Patients with Chronic Kidney Disease

  2019cites this paper
• Klotho: A Major Shareholder in Vascular Aging Enterprises

  2019cites this paper
• Modifying Phosphate Toxicity in Chronic Kidney Disease

  2019cites this paper
• Klotho and endocrine fibroblast growth factors: markers of chronic kidney disease progression and cardiovascular complications?

  2019cites this paper
• Treatment of hyperphosphatemia: the dangers of high PTH levels

  2019cites this paper
• Cholecalciferol supplementation increases FGF23 in peritoneal dialysis patients with hypovitaminosis D: a randomized clinical trial

  2019cites this paper
• Cardiovascular Disease in Renal Transplantation

  2019cites this paper
• Basic molecular mechanism of vascular calcification

  2019cites this paper
• Single Measurements of Carboxy-Terminal Fibroblast Growth Factor 23 and Clinical Risk Prediction of Adverse Outcomes in CKD.

  2019cites this paper
• Parathyroidectomy in dialysis patients: Indications, methods, and consequences

  2019cites this paper
• Arterial stiffness in chronic kidney disease: a modifiable cardiovascular risk factor?

  2019cites this paper
• Statut osseux et athérosclérose coronaire

  2019cites this paper
• Can we IMPROVE cardiovascular outcomes through phosphate lowering in CKD? Rationale and protocol for the IMpact of Phosphate Reduction On Vascular End-points in Chronic Kidney Disease (IMPROVE-CKD) study

  2019cites this paper
• Osteokines and the vasculature: a review of the in vitro effects of osteocalcin, fibroblast growth factor-23 and lipocalin-2

  2019cites this paper
• Dual Roles of the Mineral Metabolism Disorders Biomarkers in Prevalent Hemodilysis Patients: In Renal Bone Disease and in Vascular Calcification

  2019cites this paper
• Vitamin D sterols increase FGF23 expression by stimulating osteoblast and osteocyte maturation in CKD bone.

  2019cites this paper
• Strength of Fibroblast Growth Factor 23 as a Cardiovascular Risk Predictor in Chronic Kidney Disease Weaken by ProBNP Adjustment

  2019cites this paper
• Intraoperative Arterial Biopsy in Incident Hemodialysis Patients: Differences Observed

  2019cites this paper
• Estimating the distribution of a novel clinical biomarker (FGF-23) in the US population using findings from a regional research registry

  2019cites this paper
• Non-invasive diagnostic tests for renal osteodystrophy

  2019cites this paper