TY - JOUR
T1 - Prognostic Value of Fibroblast Growth Factor 23 in Autosomal Dominant Polycystic Kidney Disease
AU - El Ters, Mireille
AU - Lu, Pengcheng
AU - Mahnken, Jonathan D.
AU - Stubbs, Jason R.
AU - Zhang, Shiqin
AU - Wallace, Darren P.
AU - Grantham, Jared J.
AU - Chapman, Arlene B.
AU - Torres, Vicente E.
AU - Harris, Peter C.
AU - Bae, Kyongtae Ty
AU - Landsittel, Douglas P.
AU - Rahbari-Oskoui, Frederic F.
AU - Mrug, Michal
AU - Bennett, William M.
AU - Yu, Alan S.L.
N1 - Funding Information:
ASLY is a consultant for Regulus Therapeutics, Calico Life Sciences, and Navitor Pharmaceuticals, and has served on an advisory board for Otsuka Pharmaceuticals. VET is a member of the steering committees for the TEMPO and REPRISE clinical trials, has received research support from Otsuka Pharmaceuticals, and is a consultant for Sanofi, Reata, Palladio, Regulus Therapeutics, Mironid, and Blueprint Medicines. PCH has received research funding from Otsuka Pharmaceuticals. MM is a consultant for Otsuka, Sanofi, Chinook Therapeutics, and Natera, and has received research support from Otsuka Pharmaceuticals, Sanofi, and Chinook Therapeutics. FFR has served as a consultant and an unbranded speaker bureau member for Otsuka, is a consultant for Keryx, Kadmon, and Sanofi, and has received research funding from Otsuka, Kadmon, Sanofi, and Reata. ABC is a consultant for Otsuka, Reata, and Sanofi, and has received research funding from Boston Scientific, Kadmon, and Otsuka. All the other authors declared no competing interests.
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 . The investigators are indebted to the study coordinators in CRISP.
Publisher Copyright:
© 2021 International Society of Nephrology
PY - 2021/4
Y1 - 2021/4
N2 - 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.
AB - 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.
KW - ADPKD
KW - FGF23
UR - http://www.scopus.com/inward/record.url?scp=85101322355&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85101322355&partnerID=8YFLogxK
U2 - 10.1016/j.ekir.2021.01.004
DO - 10.1016/j.ekir.2021.01.004
M3 - Article
AN - SCOPUS:85101322355
SN - 2468-0249
VL - 6
SP - 953
EP - 961
JO - Kidney International Reports
JF - Kidney International Reports
IS - 4
ER -