TY - JOUR
T1 - Serial Fibroblast Growth Factor 23 Measurements and Risk of Requirement for Kidney Replacement Therapy
T2 - The CRIC (Chronic Renal Insufficiency Cohort) Study
AU - CRIC Study Investigators
AU - Mehta, Rupal
AU - Cai, Xuan
AU - Lee, Jungwha
AU - Xie, Dawei
AU - Wang, Xue
AU - Scialla, Julia
AU - Anderson, Amanda H.
AU - Taliercio, Jon
AU - Dobre, Mirela
AU - Chen, Jing
AU - Fischer, Michael
AU - Leonard, Mary
AU - Lash, James
AU - Hsu, Chi yuan
AU - de Boer, Ian H.
AU - Feldman, Harold I.
AU - Wolf, Myles
AU - Isakova, Tamara
AU - Appel, Lawrence J.
AU - Go, Alan S.
AU - He, Jiang
AU - Rao, Panduranga S.
AU - Rahman, Mahboob
AU - Townsend, Raymond R.
N1 - Publisher Copyright:
© 2019 National Kidney Foundation, Inc.
PY - 2020/6
Y1 - 2020/6
N2 - Rationale & Objective: Studies using a single measurement of fibroblast growth factor 23 (FGF-23) suggest that elevated FGF-23 levels are associated with increased risk for requirement for kidney replacement therapy (KRT) in patients with chronic kidney disease. However, the data do not account for changes in FGF-23 levels as kidney disease progresses. Study Design: Case-cohort study. Setting & Participants: To evaluate the association between serial FGF-23 levels and risk for requiring KRT, our primary analysis included 1,597 individuals in the Chronic Renal Insufficiency Cohort Study who had up to 5 annual measurements of carboxy-terminal FGF-23. There were 1,135 randomly selected individuals, of whom 266 initiated KRT, and 462 individuals who initiated KRT outside the random subcohort. Exposure: Serial FGF-23 measurements and FGF-23 trajectory group membership. Outcomes: Incident KRT. Analytical Approach: To handle time-dependent confounding, our primary analysis of time-updated FGF-23 levels used time-varying inverse probability weighting in a discrete time failure model. To compare our results with prior data, we used baseline and time-updated FGF-23 values in weighted Cox regression models. To examine the association of FGF-23 trajectory subgroups with risk for incident KRT, we used weighted Cox models with FGF-23 trajectory groups derived from group-based trajectory modeling as the exposure. Results: In our primary analysis, the HR for the KRT outcome per 1 SD increase in the mean of natural log–transformed (ln)FGF-23 in the past was 1.94 (95% CI, 1.51-2.49). In weighted Cox models using baseline and time-updated values, elevated FGF-23 level was associated with increased risk for incident KRT (HRs per 1 SD ln[FGF-23] of 1.18 [95% CI, 1.02-1.37] for baseline and 1.66 [95% CI, 1.49-1.86] for time-updated). Membership in the slowly and rapidly increasing FGF-23 trajectory groups was associated with ∼3- and ∼21-fold higher risk for incident KRT compared to membership in the stable FGF-23 trajectory group. Limitations: Residual confounding and lack of intact FGF-23 values. Conclusions: Increasing FGF-23 levels are independently associated with increased risk for incident KRT.
AB - Rationale & Objective: Studies using a single measurement of fibroblast growth factor 23 (FGF-23) suggest that elevated FGF-23 levels are associated with increased risk for requirement for kidney replacement therapy (KRT) in patients with chronic kidney disease. However, the data do not account for changes in FGF-23 levels as kidney disease progresses. Study Design: Case-cohort study. Setting & Participants: To evaluate the association between serial FGF-23 levels and risk for requiring KRT, our primary analysis included 1,597 individuals in the Chronic Renal Insufficiency Cohort Study who had up to 5 annual measurements of carboxy-terminal FGF-23. There were 1,135 randomly selected individuals, of whom 266 initiated KRT, and 462 individuals who initiated KRT outside the random subcohort. Exposure: Serial FGF-23 measurements and FGF-23 trajectory group membership. Outcomes: Incident KRT. Analytical Approach: To handle time-dependent confounding, our primary analysis of time-updated FGF-23 levels used time-varying inverse probability weighting in a discrete time failure model. To compare our results with prior data, we used baseline and time-updated FGF-23 values in weighted Cox regression models. To examine the association of FGF-23 trajectory subgroups with risk for incident KRT, we used weighted Cox models with FGF-23 trajectory groups derived from group-based trajectory modeling as the exposure. Results: In our primary analysis, the HR for the KRT outcome per 1 SD increase in the mean of natural log–transformed (ln)FGF-23 in the past was 1.94 (95% CI, 1.51-2.49). In weighted Cox models using baseline and time-updated values, elevated FGF-23 level was associated with increased risk for incident KRT (HRs per 1 SD ln[FGF-23] of 1.18 [95% CI, 1.02-1.37] for baseline and 1.66 [95% CI, 1.49-1.86] for time-updated). Membership in the slowly and rapidly increasing FGF-23 trajectory groups was associated with ∼3- and ∼21-fold higher risk for incident KRT compared to membership in the stable FGF-23 trajectory group. Limitations: Residual confounding and lack of intact FGF-23 values. Conclusions: Increasing FGF-23 levels are independently associated with increased risk for incident KRT.
KW - CKD progression
KW - Chronic kidney disease (CKD)
KW - biomarker
KW - dialysis
KW - disease trajectory
KW - end-stage renal disease (ESRD)
KW - fibroblast growth factor 23 (FGF-23)
KW - kidney failure
KW - kidney function decline
KW - renal replacement therapy (RRT)
KW - transplant
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U2 - 10.1053/j.ajkd.2019.09.009
DO - 10.1053/j.ajkd.2019.09.009
M3 - Article
C2 - 31864822
AN - SCOPUS:85076576049
SN - 0272-6386
VL - 75
SP - 908
EP - 918
JO - American Journal of Kidney Diseases
JF - American Journal of Kidney Diseases
IS - 6
ER -