Single Measurements of Carboxy-Terminal Fibroblast Growth Factor 23 and Clinical Risk Prediction of Adverse Outcomes in CKD.
Aged
Area Under Curve
Biomarkers
/ blood
Cause of Death
Cohort Studies
Disease-Free Survival
Female
Fibroblast Growth Factor-23
Fibroblast Growth Factors
/ blood
Humans
Kaplan-Meier Estimate
Kidney Failure, Chronic
/ blood
Male
Middle Aged
Predictive Value of Tests
Prospective Studies
ROC Curve
Renal Insufficiency, Chronic
/ blood
Risk Assessment
Survival Analysis
United States
Fibroblast growth factor 23 (FGF23)
atherosclerotic disease
biomarker
cardiovascular mortality
chronic kidney disease (CKD)
clinical risk prediction
end-stage renal disease (ESRD)
heart failure (HF)
mortality
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
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
771-781Subventions
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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