Single measurements of carboxy-terminal fibroblast growth factor 23 and clinical risk prediction of adverse outcomes in CKD
D Edmonston, D Wojdyla, R Mehta, X Cai… - American Journal of …, 2019 - Elsevier
American Journal of Kidney Diseases, 2019•Elsevier
Rationale & Objective An elevated fibroblast growth factor 23 (FGF-23) level is
independently associated with adverse outcomes in populations with chronic kidney
disease, but it is unknown whether FGF-23 testing can improve clinical risk prediction in
individuals. Study Design Prospective cohort study. Setting & Participants Participants in the
Chronic Renal Insufficiency Cohort (CRIC) Study (n= 3,789). Exposure Baseline carboxy-
terminal FGF-23 (cFGF-23) level. Outcomes All-cause and cardiovascular (CV) mortality …
independently associated with adverse outcomes in populations with chronic kidney
disease, but it is unknown whether FGF-23 testing can improve clinical risk prediction in
individuals. Study Design Prospective cohort study. Setting & Participants Participants in the
Chronic Renal Insufficiency Cohort (CRIC) Study (n= 3,789). Exposure Baseline carboxy-
terminal FGF-23 (cFGF-23) level. Outcomes All-cause and cardiovascular (CV) mortality …
Rationale & Objective
An elevated fibroblast growth factor 23 (FGF-23) level is independently associated with adverse outcomes in populations with chronic kidney disease, but it is unknown whether FGF-23 testing can improve clinical risk prediction in individuals.
Study Design
Prospective cohort study.
Setting & Participants
Participants in the Chronic Renal Insufficiency Cohort (CRIC) Study (n = 3,789).
Exposure
Baseline carboxy-terminal FGF-23 (cFGF-23) level.
Outcomes
All-cause and cardiovascular (CV) mortality, incident end-stage renal disease (ESRD), heart failure (HF) admission, and atherosclerotic events at 3, 5, and 8 years.
Analytical Approach
We assessed changes in model performance by change in area under the receiver operating characteristic curve (ΔAUC), integrated discrimination improvement (IDI), relative IDI, and net reclassification index (NRI) above standard clinical factors. We performed sensitivity analyses, including an additional model comparing the addition of phosphate rather than cFGF-23 level and repeating our analyses using an internal cross-validation cohort.
Results
Addition of a single baseline value of cFGF-23 to a base prediction model improved prediction of all-cause mortality (ΔAUC, 0.017 [95% CI, 0.001-0.033]; IDI, 0.021 [95% CI, 0.006-0.036]; relative IDI, 32.7% [95% CI, 8.5%-56.9%]), and HF admission (ΔAUC, 0.008 [95% CI, 0.0004-0.016]; IDI, 0.019 [95% CI, 0.004-0.034]; relative IDI, 10.0% [95% CI, 1.8%-18.3%]), but not CV mortality, ESRD, or atherosclerotic events at 3 years of follow-up. The NRI did not reach statistical significance for any of the 3-year outcomes. The incremental predictive utility of cFGF-23 level diminished in analyses of the 5- and 8-year outcomes. The cFGF-23 models outperformed the phosphate model for each outcome.
Limitations
Power to detect increased CV mortality likely limited by low event rate. The NRI is not generalizable without accepted prespecified risk thresholds.
Conclusions
Among individuals with CKD, single measurements of cFGF-23 improve prediction of risks for all-cause mortality and HF admission but not CV mortality, ESRD, or atherosclerotic events. Future studies should evaluate the predictive utility of repeated cFGF-23 testing.
Elsevier
