Abstract: SA-OR079
Serial FGF23 Concentrations and Risk of ESRD: The Chronic Renal Insufficiency Cohort (CRIC) Study
Session Information
- New Considerations for Renoprotection Clinical Trials
October 27, 2018 | Location: 1B, San Diego Convention Center
Abstract Time: 04:42 PM - 04:54 PM
Category: Bone and Mineral Metabolism
- 402 Bone and Mineral Metabolism: Clinical
Authors
- Mehta, Rupal, Northwestern Univesrsity, Feinberg School of Medicine, Chicago, Illinois, United States
- Cai, Xuan, Northwestern Univesrsity, Feinberg School of Medicine, Chicago, Illinois, United States
- Lee, Jungwha, Northwestern Univesrsity, Feinberg School of Medicine, Chicago, Illinois, United States
- Xie, Dawei, University of Pennsylvania School of Medicine Center for Clinical Epidemiology and Biostatistics, Philadelphia, Pennsylvania, United States
- Wang, Xue, University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Scialla, Julia J., Duke University, Durham, North Carolina, United States
- Anderson, Amanda Hyre, University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Taliercio, Jonathan J., Glickman Urological and Kidney Institute, Cleveland, Ohio, United States
- Dobre, Mirela A., Case Western Reserve University, Cleveland, Ohio, United States
- Chen, Jing, Tulane School of Medicine, New Orleans, Louisiana, United States
- Fischer, Michael J., University of Illinois Hospital and Health Sciences Center, Chicago, Illinois, United States
- Steigerwalt, Susan P., University of Michigan, Ann Arbor, Michigan, United States
- Leonard, Mary B., Stanford School of Medicine, Stanford, California, United States
- Hsu, Chi-yuan, University of California San Francisco, San Francisco, California, United States
- de Boer, Ian H., Division of Nephrology and Kidney Research Institute, University of Washington, Seattle, Washington, United States
- Lash, James P., University of Illinois at Chicago, Chicago, Illinois, United States
- Feldman, Harold I., University of Pennsylvania, Philadelphia, Pennsylvania, United States
- Wolf, Myles, Duke University, Durham, North Carolina, United States
- Isakova, Tamara, Northwestern Univesrsity, Feinberg School of Medicine, Chicago, Illinois, United States
Group or Team Name
- CRIC Study Investigators
Background
Studies using a single FGF23 value suggest that elevated plasma FGF23 is associated with increased risk of ESRD in patients with CKD. However, the data are inconsistent and do not include serial assessments of FGF23.
Methods
To test the association between serial plasma FGF23 and ESRD risk, we performed a case-cohort study within the CRIC Study. We included 1597 individuals with serial FGF23 measurements: 1135 randomly selected individuals, of whom 266 reached ESRD, and 462 individuals outside the random subcohort who also reached ESRD. FGF23 values were available at 2–5 annual time points in all individuals (mean 4.0 ± 1.2). We used weighted Cox proportional hazards models adjusted for baseline and time-varying covariates. To account for the possibility that eGFR could be a time-dependent confounder, we used marginal structural models. We performed group-based trajectory modeling and adjusted the analyses for baseline and final eGFR and eGFR trajectory.
Results
In all models using baseline and time-varying FGF23, elevated plasma FGF23 was independently associated with increased risk of ESRD (Figure). In group-based trajectory analyses, compared to individuals with plasma FGF23 in the stable trajectory group, individuals in the slowly and rapidly rising trajectory groups were at ~3-fold and ~22-fold greater risk of ESRD (Table).
Conclusion
In multiple modeling approaches using serial FGF23 measurements, elevated plasma FGF23 was independently associated with risk of ESRD. Mechanistic studies are needed to test whether exposure to elevated and rising FGF23 levels contributes to accelerated CKD progression.
Funding
- NIDDK Support