Single Measurements of Carboxy-Terminal Fibroblast Growth Factor 23 and Clinical Risk Prediction of Adverse Outcomes in CKD.


Journal

American journal of kidney diseases : the official journal of the National Kidney Foundation
ISSN: 1523-6838
Titre abrégé: Am J Kidney Dis
Pays: United States
ID NLM: 8110075

Informations de publication

Date de publication:
12 2019
Historique:
received: 04 07 2018
accepted: 13 05 2019
pubmed: 26 8 2019
medline: 9 4 2020
entrez: 26 8 2019
Statut: ppublish

Résumé

An elevated fibroblast growth factor 23 (FGF-23) level is independently associated with adverse outcomes in populations with chronic kidney disease, but it is unknown whether FGF-23 testing can improve clinical risk prediction in individuals. Prospective cohort study. Participants in the Chronic Renal Insufficiency Cohort (CRIC) Study (n = 3,789). Baseline carboxy-terminal FGF-23 (cFGF-23) level. All-cause and cardiovascular (CV) mortality, incident end-stage renal disease (ESRD), heart failure (HF) admission, and atherosclerotic events at 3, 5, and 8 years. We assessed changes in model performance by change in area under the receiver operating characteristic curve (ΔAUC), integrated discrimination improvement (IDI), relative IDI, and net reclassification index (NRI) above standard clinical factors. We performed sensitivity analyses, including an additional model comparing the addition of phosphate rather than cFGF-23 level and repeating our analyses using an internal cross-validation cohort. Addition of a single baseline value of cFGF-23 to a base prediction model improved prediction of all-cause mortality (ΔAUC, 0.017 [95% CI, 0.001-0.033]; IDI, 0.021 [95% CI, 0.006-0.036]; relative IDI, 32.7% [95% CI, 8.5%-56.9%]), and HF admission (ΔAUC, 0.008 [95% CI, 0.0004-0.016]; IDI, 0.019 [95% CI, 0.004-0.034]; relative IDI, 10.0% [95% CI, 1.8%-18.3%]), but not CV mortality, ESRD, or atherosclerotic events at 3 years of follow-up. The NRI did not reach statistical significance for any of the 3-year outcomes. The incremental predictive utility of cFGF-23 level diminished in analyses of the 5- and 8-year outcomes. The cFGF-23 models outperformed the phosphate model for each outcome. Power to detect increased CV mortality likely limited by low event rate. The NRI is not generalizable without accepted prespecified risk thresholds. Among individuals with CKD, single measurements of cFGF-23 improve prediction of risks for all-cause mortality and HF admission but not CV mortality, ESRD, or atherosclerotic events. Future studies should evaluate the predictive utility of repeated cFGF-23 testing.

Identifiants

pubmed: 31445926
pii: S0272-6386(19)30848-0
doi: 10.1053/j.ajkd.2019.05.026
pmc: PMC6875624
mid: NIHMS1535676
pii:
doi:

Substances chimiques

Biomarkers 0
FGF23 protein, human 0
Fibroblast Growth Factors 62031-54-3
Fibroblast Growth Factor-23 7Q7P4S7RRE

Types de publication

Journal Article Multicenter Study Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

771-781

Subventions

Organisme : NIDDK NIH HHS
ID : R01 DK072231
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR002548
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK060963
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR024131
Pays : United States
Organisme : NCRR NIH HHS
ID : M01 RR013987
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000003
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000439
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK060990
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK110087
Pays : United States
Organisme : NCRR NIH HHS
ID : UL1 RR029879
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK061028
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000433
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK060984
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK061021
Pays : United States
Organisme : NIDDK NIH HHS
ID : U24 DK060990
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK060980
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001422
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK061022
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK081374
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR000424
Pays : United States
Organisme : NCRR NIH HHS
ID : M01 RR016500
Pays : United States
Organisme : NIGMS NIH HHS
ID : P20 GM109036
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK060902
Pays : United States

Investigateurs

Lawrence J Appel (LJ)
Harold I Feldman (HI)
James P Lash (JP)
Panduranga S Rao (PS)
Mahboob Rahman (M)
Matthew R Weir (MR)
Claudia Lora (C)
Debbie Cohen (D)
Raymond R Townsend (RR)
Jiang He (J)
Alan Go (A)
John Kusek (J)

Informations de copyright

Copyright © 2019 National Kidney Foundation, Inc. All rights reserved.

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Auteurs

Daniel Edmonston (D)

Division of Nephrology, Department of Medicine, Durham, NC; Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.

Daniel Wojdyla (D)

Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC.

Rupal Mehta (R)

Division of Nephrology and Hypertension, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL; Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.

Xuan Cai (X)

Division of Nephrology and Hypertension, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.

Claudia Lora (C)

Department of Medicine, University of Illinois at Chicago, Chicago, IL.

Debbie Cohen (D)

Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, Department of Medicine, University of Pennsylvania, Philadelphia, PA.

Raymond R Townsend (RR)

Renal-Electrolyte and Hypertension Division, Perelman School of Medicine, Department of Medicine, University of Pennsylvania, Philadelphia, PA.

Jiang He (J)

Department of Epidemiology, Tulane University School of Public Health and Tropical Medicine, New Orleans, LA.

Alan S Go (AS)

Kaiser Permanente Northern California Division of Research, Oakland, CA.

John Kusek (J)

National Institutes of Health, Bethesda.

Matthew R Weir (MR)

Division of Nephrology, Department of Medicine, University of Maryland School of Medicine, Baltimore, MD.

Tamara Isakova (T)

Division of Nephrology and Hypertension, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL; Center for Translational Metabolism and Health, Institute for Public Health and Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL.

Michael Pencina (M)

Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC; Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC.

Myles Wolf (M)

Division of Nephrology, Department of Medicine, Durham, NC; Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC. Electronic address: myles.wolf@duke.edu.

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Classifications MeSH