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J Am Soc Nephrol. 2018 Feb;29(2):579-590. doi: 10.1681/ASN.2017070772. Epub 2017 Nov 22.

Longitudinal FGF23 Trajectories and Mortality in Patients with CKD.

Author information

1
Division of Nephrology and Hypertension, Department of Medicine and.
2
Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Department of Preventive Medicine Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
3
Department of Biostatistics, Epidemiology and Informatics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania.
4
Division of Nephrology, Department of Medicine and.
5
Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.
6
Department of Nephrology and Hypertension, Cleveland Clinic, Cleveland, Ohio.
7
Department of Medicine, Tulane University School of Medicine, New Orleans, Louisiana.
8
Division of Nephrology, Department of Medicine, University of Illinois at Chicago College of Medicine, Jesse Brown Veterans Affairs Medical Center, Chicago, Illinois.
9
Center of Innovation for Complex Chronic Healthcare, Edward Hines Jr. Veterans Affairs Hospital, Hines, Illinois.
10
Division of Nephrology, University of Michigan School of Medicine, Ann Arbor, Michigan.
11
Departments of Pediatrics and.
12
Medicine, Stanford University, Stanford, California.
13
Division of Nephrology, Department of Medicine, University of California, San Francisco, San Francisco, California.
14
Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington; and.
15
National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland.
16
Division of Nephrology, Department of Medicine and tamara.isakova@northwestern.edu myles.wolf@duke.edu.

Abstract

Elevated fibroblast growth factor 23 (FGF23) levels, measured at a single time, are strongly associated with increased risk of mortality in patients with CKD. There are minimal data on serial FGF23 measurements in CKD. In a prospective case-cohort study of the Chronic Renal Insufficiency Cohort, we measured FGF23 at two to five annual time points (mean 4.0±1.2) in a randomly selected subcohort of 1135 participants, of whom 203 died, and all remaining 390 participants who died through mid-2013. Higher FGF23 was independently associated with increased risk of death in multivariable-adjusted analyses of time-varying FGF23 (hazard ratio per 1-SD increase in ln-transformed FGF23, 1.84; 95% CI, 1.67 to 2.03). Median FGF23 was stable over 5 years of follow-up, but its gradually right-skewed distribution suggested a subpopulation with markedly elevated FGF23. Trajectory analysis revealed three distinct trajectories: stable FGF23 in the majority of participants (slope of lnFGF23 per year =0.03, 95% CI, 0.02 to 0.04, n=724) and smaller subpopulations with slowly (slope=0.14, 95% CI, 0.12 to 0.16, n=486) or rapidly (slope=0.46, 95% CI, 0.38 to 0.54, n=99) rising levels. Compared with stable FGF23, participants with slowly rising FGF23 trajectories were at 4.49-fold higher risk of death (95% CI, 3.17 to 6.35) and individuals with rapidly rising FGF23 trajectories were at 15.23-fold higher risk of death (95% CI, 8.24 to 28.14) in fully adjusted analyses. Trajectory analyses that used four or three annual FGF23 measurements yielded qualitatively similar results. In conclusion, FGF23 levels are stable over time in the majority of patients with CKD, but serial measurements identify subpopulations with rising levels and exceptionally high risk of death.

KEYWORDS:

CKD; FGF23; mortality risk

PMID:
29167351
PMCID:
PMC5791067
[Available on 2019-02-01]
DOI:
10.1681/ASN.2017070772

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