Prognostic Value of Fibroblast Growth Factor 23 in Autosomal Dominant Polycystic Kidney Disease

• Type of Material: Article
• Authors: Mireille El Ters, University of Kansas; Pengcheng Lu, University of Kansas; Jonathan D. Mahnken, University of Kansas; Jason R. Stubbs, University of Kansas; Shiqin Zhang, University of Kansas; Darren P. Wallace, University of Kansas; Jared J. Grantham, University of Kansas; Arlene Chapman, Emory University; Vicente Torres, Mayo Clinic; Peter C. Harris, Mayo Clinic; Kyongtae Bae, University of Pittsburgh; Douglas P. Landsittel, University of Pittsburgh; Frederic Rahbari Oskoui, Emory University; Michal Mrug, University of Alabama Birmingham; William M. Bennett, Legacy Good Samaritan Hosp; Alan S. L. Yu, University of Kansas
• Language: English
• Date: 2021-04-05
• Publisher: Elsevier Science Inc.
• Publication Version: Final Published Version
• Copyright Statement: © 2021 International Society of Nephrology. Published by Elsevier Inc.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ekir.2021.01.004
• Title of Journal or Parent Work: Kidney International Response
• Volume: 6
• Issue: 4
• Start Page: 953
• End Page: 961
• Grant/Funding Information: Supported by a Clinical and Translational Science award from the National Center for Advancing Translational Sciences to the University of Kansas Medical Center for Frontiers; The Heartland Institute for Clinical and Translational Research (UL1TR000001), by the University of Kansas Medical Center Research Institute, and by National Institute of Diabetes and Digestive and Kidney Diseases grants to the Kansas PKD Research and Translation Core Center (P30 DK106912 and U54 DK126126).; The CRISP study is supported by cooperative agreements from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health (DK056943, DK056956, DK056957, and DK056961), and by R01 DK113111.
• Keywords: Klotho; Renal disease; Life Sciences & Biomedicine; Volume; FGF23; Urology & Nephrology; FGF-23; MRI; Science & Technology; ADPKD; Progression
• Research Categories: Biology, Biostatistics; Health Sciences, Radiology; Engineering, Biomedical; Biology, Bioinformatics

Abstract

Introduction Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst growth and a loss of functioning renal mass, but a decline in glomerular filtration rate (GFR) and onset of end-stage renal disease (ESRD) occur late in the disease course. There is therefore a great need for early prognostic biomarkers in this disorder. Methods We measured baseline serum fibroblast growth factor 23 (FGF23) levels in 192 patients with ADPKD from the Consortium for Radiologic Imaging Studies of PKD (CRISP) cohort that were followed for a median of 13 years and tested the association between FGF23 levels and change over time in height-adjusted total kidney volume (htTKV), GFR, and time to the composite endpoints of ESRD, death, and doubling of serum creatinine. Results Patients in the highest quartile for baseline FGF23 level had a higher rate of increase in htTKV (0.95% per year, P = 0.0016), and faster rate of decline in GFR (difference of −1.03 ml/min/1.73 m2 per year, P = 0.005) compared with the lowest quartile, after adjusting for other covariates, including htTKV and genotype. The highest quartile of FGF23 was also associated with a substantial increase in risk for the composite endpoint of ESRD, death, or doubling of serum creatinine (hazard ratio [HR] of 2.45 in the fully adjusted model, P = 0.03). Conclusion FGF23 is a prognostic biomarker for disease progression and clinically important outcomes in ADPKD, and has additive value to established imaging and genetic biomarkers.