Longitudinal change in c-terminal fibroblast growth factor 23 and outcomes in patients with advanced chronic kidney disease

Abstract Background Fibroblast growth factor23 (FGF23) is elevated in CKD and has been associated with outcomes such as death, cardiovascular (CV) events and progression to Renal Replacement therapy (RRT). The majority of studies have been unable to account for change in FGF23 over time and those wh...

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Main Authors: Helen V. Alderson, Rajkumar Chinnadurai, Sara T. Ibrahim, Ozgur Asar, James P. Ritchie, Rachel Middleton, Anders Larsson, Peter J. Diggle, Tobias E. Larsson, Philip A. Kalra
Format: Article
Language:English
Published: BMC 2021-10-01
Series:BMC Nephrology
Subjects:
CKD
Online Access:https://doi.org/10.1186/s12882-021-02528-2
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spelling doaj-ec22bf7e906a4671bdc03c893b33bbc72021-10-03T11:58:23ZengBMCBMC Nephrology1471-23692021-10-012211710.1186/s12882-021-02528-2Longitudinal change in c-terminal fibroblast growth factor 23 and outcomes in patients with advanced chronic kidney diseaseHelen V. Alderson0Rajkumar Chinnadurai1Sara T. Ibrahim2Ozgur Asar3James P. Ritchie4Rachel Middleton5Anders Larsson6Peter J. Diggle7Tobias E. Larsson8Philip A. Kalra9Vascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Salford Royal NHS Foundation TrustVascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Salford Royal NHS Foundation TrustVascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Salford Royal NHS Foundation TrustDepartment of Biostatistics and Medical Informatics, Acibadem Mehmet Ali Aydinlar UniversityVascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Salford Royal NHS Foundation TrustVascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Salford Royal NHS Foundation TrustSection of Clinical Chemistry, Department of Medical Sciences, Uppsala UniversityCHICAS, Lancaster Medical School, Lancaster UniversityDepartment of Clinical Science, Intervention and Technology, Renal Unit, Karolinska InstituteVascular Research Group, Manchester Academic Health Sciences Centre, University of Manchester, Salford Royal NHS Foundation TrustAbstract Background Fibroblast growth factor23 (FGF23) is elevated in CKD and has been associated with outcomes such as death, cardiovascular (CV) events and progression to Renal Replacement therapy (RRT). The majority of studies have been unable to account for change in FGF23 over time and those which have demonstrate conflicting results. We performed a survival analysis looking at change in c-terminal FGF23 (cFGF23) over time to assess the relative contribution of cFGF23 to these outcomes. Methods We measured cFGF23 on plasma samples from 388 patients with CKD 3-5 who had serial measurements of cFGF23, with a mean of 4.2 samples per individual. We used linear regression analysis to assess the annual rate of change in cFGF23 and assessed the relationship between time-varying cFGF23 and the outcomes in a cox-regression analysis. Results Across our population, median baseline eGFR was 32.3mls/min/1.73m2, median baseline cFGF23 was 162 relative units/ml (RU/ml) (IQR 101-244 RU/mL). Over 70 months (IQR 53-97) median follow-up, 76 (19.6%) patients progressed to RRT, 86 (22.2%) died, and 52 (13.4%) suffered a major non-fatal CV event. On multivariate analysis, longitudinal change in cFGF23 was significantly associated with risk for death and progression to RRT but not non-fatal cardiovascular events. Conclusion In our study, increasing cFGF23 was significantly associated with risk for death and RRT.https://doi.org/10.1186/s12882-021-02528-2cFGF23CKDSurvival outcomes
collection DOAJ
language English
format Article
sources DOAJ
author Helen V. Alderson
Rajkumar Chinnadurai
Sara T. Ibrahim
Ozgur Asar
James P. Ritchie
Rachel Middleton
Anders Larsson
Peter J. Diggle
Tobias E. Larsson
Philip A. Kalra
spellingShingle Helen V. Alderson
Rajkumar Chinnadurai
Sara T. Ibrahim
Ozgur Asar
James P. Ritchie
Rachel Middleton
Anders Larsson
Peter J. Diggle
Tobias E. Larsson
Philip A. Kalra
Longitudinal change in c-terminal fibroblast growth factor 23 and outcomes in patients with advanced chronic kidney disease
BMC Nephrology
cFGF23
CKD
Survival outcomes
author_facet Helen V. Alderson
Rajkumar Chinnadurai
Sara T. Ibrahim
Ozgur Asar
James P. Ritchie
Rachel Middleton
Anders Larsson
Peter J. Diggle
Tobias E. Larsson
Philip A. Kalra
author_sort Helen V. Alderson
title Longitudinal change in c-terminal fibroblast growth factor 23 and outcomes in patients with advanced chronic kidney disease
title_short Longitudinal change in c-terminal fibroblast growth factor 23 and outcomes in patients with advanced chronic kidney disease
title_full Longitudinal change in c-terminal fibroblast growth factor 23 and outcomes in patients with advanced chronic kidney disease
title_fullStr Longitudinal change in c-terminal fibroblast growth factor 23 and outcomes in patients with advanced chronic kidney disease
title_full_unstemmed Longitudinal change in c-terminal fibroblast growth factor 23 and outcomes in patients with advanced chronic kidney disease
title_sort longitudinal change in c-terminal fibroblast growth factor 23 and outcomes in patients with advanced chronic kidney disease
publisher BMC
series BMC Nephrology
issn 1471-2369
publishDate 2021-10-01
description Abstract Background Fibroblast growth factor23 (FGF23) is elevated in CKD and has been associated with outcomes such as death, cardiovascular (CV) events and progression to Renal Replacement therapy (RRT). The majority of studies have been unable to account for change in FGF23 over time and those which have demonstrate conflicting results. We performed a survival analysis looking at change in c-terminal FGF23 (cFGF23) over time to assess the relative contribution of cFGF23 to these outcomes. Methods We measured cFGF23 on plasma samples from 388 patients with CKD 3-5 who had serial measurements of cFGF23, with a mean of 4.2 samples per individual. We used linear regression analysis to assess the annual rate of change in cFGF23 and assessed the relationship between time-varying cFGF23 and the outcomes in a cox-regression analysis. Results Across our population, median baseline eGFR was 32.3mls/min/1.73m2, median baseline cFGF23 was 162 relative units/ml (RU/ml) (IQR 101-244 RU/mL). Over 70 months (IQR 53-97) median follow-up, 76 (19.6%) patients progressed to RRT, 86 (22.2%) died, and 52 (13.4%) suffered a major non-fatal CV event. On multivariate analysis, longitudinal change in cFGF23 was significantly associated with risk for death and progression to RRT but not non-fatal cardiovascular events. Conclusion In our study, increasing cFGF23 was significantly associated with risk for death and RRT.
topic cFGF23
CKD
Survival outcomes
url https://doi.org/10.1186/s12882-021-02528-2
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