Fibroblast Growth Factor 23 and Risks of Mortality and End-stage Renal Disease in Patients with Chronic Kidney Disease

Overview

Journal JAMA

Publisher American Medical Association

Specialty General Medicine

Date 2011 Jun 16

PMID 21673295

Citations 505

Authors

Tamara Isakova

Huiliang Xie

Wei Yang

Dawei Xie

Amanda Hyre Anderson

Julia Scialla

Patricia Wahl

Orlando M Gutierrez

Susan Steigerwalt

Jiang He

Stanley Schwartz

Joan Lo

Akinlolu Ojo

James Sondheimer

Chi-Yuan Hsu

James Lash

Mary Leonard

John W Kusek

Harold I Feldman

Myles Wolf

Affiliations

Soon will be listed here.

Abstract

Context: A high level of the phosphate-regulating hormone fibroblast growth factor 23 (FGF-23) is associated with mortality in patients with end-stage renal disease, but little is known about its relationship with adverse outcomes in the much larger population of patients with earlier stages of chronic kidney disease.

Objective: To evaluate FGF-23 as a risk factor for adverse outcomes in patients with chronic kidney disease.

Design, Setting, And Participants: A prospective study of 3879 participants with chronic kidney disease stages 2 through 4 who enrolled in the Chronic Renal Insufficiency Cohort between June 2003 and September 2008.

Main Outcome Measures: All-cause mortality and end-stage renal disease.

Results: At study enrollment, the mean (SD) estimated glomerular filtration rate (GFR) was 42.8 (13.5) mL/min/1.73 m(2), and the median FGF-23 level was 145.5 RU/mL (interquartile range [IQR], 96-239 reference unit [RU]/mL). During a median follow-up of 3.5 years (IQR, 2.5-4.4 years), 266 participants died (20.3/1000 person-years) and 410 reached end-stage renal disease (33.0/1000 person-years). In adjusted analyses, higher levels of FGF-23 were independently associated with a greater risk of death (hazard ratio [HR], per SD of natural log-transformed FGF-23, 1.5; 95% confidence interval [CI], 1.3-1.7). Mortality risk increased by quartile of FGF-23: the HR was 1.3 (95% CI, 0.8-2.2) for the second quartile, 2.0 (95% CI, 1.2-3.3) for the third quartile, and 3.0 (95% CI, 1.8-5.1) for the fourth quartile. Elevated fibroblast growth factor 23 was independently associated with significantly higher risk of end-stage renal disease among participants with an estimated GFR between 30 and 44 mL/min/1.73 m(2) (HR, 1.3 per SD of FGF-23 natural log-transformed FGF-23; 95% CI, 1.04-1.6) and 45 mL/min/1.73 m(2) or higher (HR, 1.7; 95% CI, 1.1-2.4), but not less than 30 mL/min/1.73 m(2).

Conclusion: Elevated FGF-23 is an independent risk factor for end-stage renal disease in patients with relatively preserved kidney function and for mortality across the spectrum of chronic kidney disease.

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References

Wolf M . Forging forward with 10 burning questions on FGF23 in kidney disease. J Am Soc Nephrol. 2010; 21(9):1427-35. DOI: 10.1681/ASN.2009121293. View

Juppner H, Wolf M, Salusky I . FGF-23: More than a regulator of renal phosphate handling?. J Bone Miner Res. 2010; 25(10):2091-7. PMC: 3153315. DOI: 10.1002/jbmr.170. View

Fliser D, Kollerits B, Neyer U, Ankerst D, Lhotta K, Lingenhel A . Fibroblast growth factor 23 (FGF23) predicts progression of chronic kidney disease: the Mild to Moderate Kidney Disease (MMKD) Study. J Am Soc Nephrol. 2007; 18(9):2600-8. DOI: 10.1681/ASN.2006080936. View

Gutierrez O, Isakova T, Rhee E, Shah A, Holmes J, Collerone G . Fibroblast growth factor-23 mitigates hyperphosphatemia but accentuates calcitriol deficiency in chronic kidney disease. J Am Soc Nephrol. 2005; 16(7):2205-15. DOI: 10.1681/ASN.2005010052. View

Mirza M, Hansen T, Johansson L, Ahlstrom H, Larsson A, Lind L . Relationship between circulating FGF23 and total body atherosclerosis in the community. Nephrol Dial Transplant. 2009; 24(10):3125-31. DOI: 10.1093/ndt/gfp205. View

Mirza M, Larsson A, Melhus H, Lind L, Larsson T . Serum intact FGF23 associate with left ventricular mass, hypertrophy and geometry in an elderly population. Atherosclerosis. 2009; 207(2):546-51. DOI: 10.1016/j.atherosclerosis.2009.05.013. View

Wesseling-Perry K, Pereira R, Sahney S, Gales B, Wang H, Elashoff R . Calcitriol and doxercalciferol are equivalent in controlling bone turnover, suppressing parathyroid hormone, and increasing fibroblast growth factor-23 in secondary hyperparathyroidism. Kidney Int. 2010; 79(1):112-9. DOI: 10.1038/ki.2010.352. View

Komaba H, Goto S, Fujii H, Hamada Y, Kobayashi A, Shibuya K . Depressed expression of Klotho and FGF receptor 1 in hyperplastic parathyroid glands from uremic patients. Kidney Int. 2009; 77(3):232-8. DOI: 10.1038/ki.2009.414. View

Teng M, Wolf M, Lowrie E, Ofsthun N, Lazarus J, Thadhani R . Survival of patients undergoing hemodialysis with paricalcitol or calcitriol therapy. N Engl J Med. 2003; 349(5):446-56. DOI: 10.1056/NEJMoa022536. View

10.

Gutierrez O, Januzzi J, Isakova T, Laliberte K, Smith K, Collerone G . Fibroblast growth factor 23 and left ventricular hypertrophy in chronic kidney disease. Circulation. 2009; 119(19):2545-52. PMC: 2740903. DOI: 10.1161/CIRCULATIONAHA.108.844506. View

11.

Titan S, Zatz R, Graciolli F, Dos Reis L, Barros R, Jorgetti V . FGF-23 as a predictor of renal outcome in diabetic nephropathy. Clin J Am Soc Nephrol. 2010; 6(2):241-7. PMC: 3052212. DOI: 10.2215/CJN.04250510. View

12.

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

13.

Isakova T, Wahl P, Vargas G, Gutierrez O, Scialla J, Xie H . Fibroblast growth factor 23 is elevated before parathyroid hormone and phosphate in chronic kidney disease. Kidney Int. 2011; 79(12):1370-8. PMC: 3134393. DOI: 10.1038/ki.2011.47. View

14.

Isakova T, Gutierrez O, Chang Y, Shah A, Tamez H, Smith K . Phosphorus binders and survival on hemodialysis. J Am Soc Nephrol. 2008; 20(2):388-96. PMC: 2637053. DOI: 10.1681/ASN.2008060609. View

15.

Mirza M, Larsson A, Lind L, Larsson T . Circulating fibroblast growth factor-23 is associated with vascular dysfunction in the community. Atherosclerosis. 2009; 205(2):385-90. DOI: 10.1016/j.atherosclerosis.2009.01.001. View

16.

Kestenbaum B, Sampson J, Rudser K, Patterson D, Seliger S, Young B . Serum phosphate levels and mortality risk among people with chronic kidney disease. J Am Soc Nephrol. 2004; 16(2):520-8. DOI: 10.1681/ASN.2004070602. View

17.

Landray M, Emberson J, Blackwell L, Dasgupta T, Zakeri R, Morgan M . Prediction of ESRD and death among people with CKD: the Chronic Renal Impairment in Birmingham (CRIB) prospective cohort study. Am J Kidney Dis. 2010; 56(6):1082-94. PMC: 2991589. DOI: 10.1053/j.ajkd.2010.07.016. View

18.

Shimada T, Urakawa I, Isakova T, Yamazaki Y, Epstein M, Wesseling-Perry K . Circulating fibroblast growth factor 23 in patients with end-stage renal disease treated by peritoneal dialysis is intact and biologically active. J Clin Endocrinol Metab. 2009; 95(2):578-85. PMC: 2840849. DOI: 10.1210/jc.2009-1603. View

19.

Jean G, Terrat J, Vanel T, Hurot J, Lorriaux C, Mayor B . High levels of serum fibroblast growth factor (FGF)-23 are associated with increased mortality in long haemodialysis patients. Nephrol Dial Transplant. 2009; 24(9):2792-6. DOI: 10.1093/ndt/gfp191. View

20.

Feldman H, Appel L, Chertow G, Cifelli D, Cizman B, Daugirdas J . The Chronic Renal Insufficiency Cohort (CRIC) Study: Design and Methods. J Am Soc Nephrol. 2003; 14(7 Suppl 2):S148-53. DOI: 10.1097/01.asn.0000070149.78399.ce. View