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Plasma FGF23 and Calcified Atherosclerotic Plaque in African Americans with Type 2 Diabetes Mellitus

Overview

Overview

Journal Am J Nephrol

Publisher Karger

Specialty Nephrology

Date 2015 Dec 24

PMID 26693712

Citations 16

Authors

Authors

Barry I Freedman

Jasmin Divers

Gregory B Russell

Nicholette D Palmer

Donald W Bowden

J Jeffrey Carr

Lynne E Wagenknecht

R Caresse Hightower

Jianzhao Xu

Susan Carrie Smith

Carl D Langefeld

Keith A Hruska

Thomas C Register

Affiliations

Affiliations

Soon will be listed here.

Abstract

Background: Fibroblast growth factor 23 (FGF23) is a phosphaturic hormone implicated in disorders of serum phosphorus concentration and vitamin D. The role of FGF23 in vascular calcification remains controversial.

Methods: Relationships between FGF23 and coronary artery calcified atherosclerotic plaque (CAC), aortoiliac calcified plaque (CP), carotid artery CP, volumetric bone mineral density (vBMD), albuminuria, and estimated glomerular filtration rate (eGFR) were determined in 545 African Americans with type 2 diabetes (T2D) and preserved kidney function in African American-Diabetes Heart Study participants. Generalized linear models were fitted to test associations between FGF23 and cardiovascular, bone, and renal phenotypes, and change in measurements over time, adjusting for age, gender, African ancestry proportion, body mass index, diabetes duration, hemoglobin A1c, blood pressure, renin-angiotensin-system inhibitors, statins, calcium supplements, serum calcium, and serum phosphate.

Results: The sample was 56.7% female with a mean (SD) age of 55.6 (9.6) years, diabetes duration of 10.3 (8.2) years, eGFR 90.9 (22.1) ml/min/1.73 m2, urine albumin:creatinine ratio (UACR) 151 (588) (median 13) mg/g, plasma FGF23 161 (157) RU/ml, and CAC 637 (1,179) mg. In fully adjusted models, FGF23 was negatively associated with eGFR (p < 0.0001) and positively associated with UACR (p < 0.0001) and CAC (p = 0.0006), but not with carotid CP or aortic CP. Baseline FGF23 concentration did not associate with changes in vBMD or CAC after a mean of 5.1 years follow-up.

Conclusions: Plasma FGF23 concentrations were independently associated with subclinical coronary artery disease, albuminuria, and kidney function in the understudied African American population with T2D. Findings support relationships between FGF23 and vascular calcification, but not between FGF23 and bone mineral density, in African Americans lacking advanced nephropathy.

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References

1.

Fang Y, Ginsberg C, Seifert M, Agapova O, Sugatani T, Register T . CKD-induced wingless/integration1 inhibitors and phosphorus cause the CKD-mineral and bone disorder. J Am Soc Nephrol. 2014; 25(8):1760-73. PMC: 4116062. DOI: 10.1681/ASN.2013080818. View

2.

Sabbagh Y, Graciolli F, OBrien S, Tang W, Dos Reis L, Ryan S . Repression of osteocyte Wnt/β-catenin signaling is an early event in the progression of renal osteodystrophy. J Bone Miner Res. 2012; 27(8):1757-72. DOI: 10.1002/jbmr.1630. View

3.

Papademetriou V, Lovato L, Doumas M, Nylen E, Mottl A, Cohen R . Chronic kidney disease and intensive glycemic control increase cardiovascular risk in patients with type 2 diabetes. Kidney Int. 2014; 87(3):649-59. DOI: 10.1038/ki.2014.296. View

4.

Schoppet M, Hofbauer L, Brinskelle-Schmal N, Varennes A, Goudable J, Richard M . Serum level of the phosphaturic factor FGF23 is associated with abdominal aortic calcification in men: the STRAMBO study. J Clin Endocrinol Metab. 2012; 97(4):E575-83. DOI: 10.1210/jc.2011-2836. View

5.

Razzaque M, Sitara D, Taguchi T, St-Arnaud R, Lanske B . Premature aging-like phenotype in fibroblast growth factor 23 null mice is a vitamin D-mediated process. FASEB J. 2006; 20(6):720-2. PMC: 2899884. DOI: 10.1096/fj.05-5432fje. View

6.

Freedman B, Register T . Effect of race and genetics on vitamin D metabolism, bone and vascular health. Nat Rev Nephrol. 2012; 8(8):459-66. PMC: 10032380. DOI: 10.1038/nrneph.2012.112. View

7.

Register T, Divers J, Bowden D, Carr J, Lenchik L, Wagenknecht L . Relationships between serum adiponectin and bone density, adiposity and calcified atherosclerotic plaque in the African American-Diabetes Heart Study. J Clin Endocrinol Metab. 2013; 98(5):1916-22. PMC: 3644610. DOI: 10.1210/jc.2012-4126. View

8.

Parker B, Schurgers L, Brandenburg V, Christenson R, Vermeer C, Ketteler M . The associations of fibroblast growth factor 23 and uncarboxylated matrix Gla protein with mortality in coronary artery disease: the Heart and Soul Study. Ann Intern Med. 2010; 152(10):640-8. PMC: 3079370. DOI: 10.7326/0003-4819-152-10-201005180-00004. View

9.

Rebholz C, Grams M, Coresh J, Selvin E, Inker L, Levey A . Serum fibroblast growth factor-23 is associated with incident kidney disease. J Am Soc Nephrol. 2014; 26(1):192-200. PMC: 4279743. DOI: 10.1681/ASN.2014020218. View

10.

Dominguez J, Shlipak M, Whooley M, Ix J . Fractional excretion of phosphorus modifies the association between fibroblast growth factor-23 and outcomes. J Am Soc Nephrol. 2013; 24(4):647-54. PMC: 3609138. DOI: 10.1681/ASN.2012090894. View

11.

Meir T, Durlacher K, Pan Z, Amir G, Richards W, Silver J . Parathyroid hormone activates the orphan nuclear receptor Nurr1 to induce FGF23 transcription. Kidney Int. 2014; 86(6):1106-15. DOI: 10.1038/ki.2014.215. View

12.

Coen G, De Paolis P, Ballanti P, Pierantozzi A, Pisano S, Sardella D . Peripheral artery calcifications evaluated by histology correlate to those detected by CT: relationships with fetuin-A and FGF-23. J Nephrol. 2010; 24(3):313-21. DOI: 10.5301/JN.2010.5818. View

13.

Inaba M, Okuno S, Imanishi Y, Yamada S, Shioi A, Yamakawa T . Role of fibroblast growth factor-23 in peripheral vascular calcification in non-diabetic and diabetic hemodialysis patients. Osteoporos Int. 2006; 17(10):1506-13. DOI: 10.1007/s00198-006-0154-6. View

14.

Scialla J, Xie H, Rahman M, Anderson A, Isakova T, Ojo A . Fibroblast growth factor-23 and cardiovascular events in CKD. J Am Soc Nephrol. 2013; 25(2):349-60. PMC: 3904568. DOI: 10.1681/ASN.2013050465. View

15.

Silswal N, Touchberry C, Daniel D, McCarthy D, Zhang S, Andresen J . FGF23 directly impairs endothelium-dependent vasorelaxation by increasing superoxide levels and reducing nitric oxide bioavailability. Am J Physiol Endocrinol Metab. 2014; 307(5):E426-36. PMC: 4154070. DOI: 10.1152/ajpendo.00264.2014. View

16.

Isakova T, Xie H, Yang W, Xie D, Anderson A, Scialla J . Fibroblast growth factor 23 and risks of mortality and end-stage renal disease in patients with chronic kidney disease. JAMA. 2011; 305(23):2432-9. PMC: 3124770. DOI: 10.1001/jama.2011.826. View

17.

Freedman B, Wagenknecht L, Hairston K, Bowden D, Carr J, Hightower R . Vitamin d, adiposity, and calcified atherosclerotic plaque in african-americans. J Clin Endocrinol Metab. 2010; 95(3):1076-83. PMC: 2841532. DOI: 10.1210/jc.2009-1797. View

18.

Lim K, Lu T, Molostvov G, Lee C, Lam F, Zehnder D . Vascular Klotho deficiency potentiates the development of human artery calcification and mediates resistance to fibroblast growth factor 23. Circulation. 2012; 125(18):2243-55. DOI: 10.1161/CIRCULATIONAHA.111.053405. View

19.

Carr J, Register T, Hsu F, Lohman K, Lenchik L, Bowden D . Calcified atherosclerotic plaque and bone mineral density in type 2 diabetes: the diabetes heart study. Bone. 2007; 42(1):43-52. PMC: 2239236. DOI: 10.1016/j.bone.2007.08.023. View

20.

Andrukhova O, Slavic S, Smorodchenko A, Zeitz U, Shalhoub V, Lanske B . FGF23 regulates renal sodium handling and blood pressure. EMBO Mol Med. 2014; 6(6):744-59. PMC: 4203353. DOI: 10.1002/emmm.201303716. View