Fibroblast Growth Factor 23 Associates with Death in Critically III Patients
- 6 April 2018
- journal article
- research article
- Published by Ovid Technologies (Wolters Kluwer Health) in Clinical Journal of the American Society of Nephrology
- Vol. 13 (4), 531-541
- https://doi.org/10.2215/CJN.10810917
Abstract
Background and objectives Dysregulated mineral metabolism is a common and potentially maladaptive feature of critical illness, especially in patients with AKI, but its association with death has not been comprehensively investigated. We sought to determine whether elevated plasma levels of the osteocyte-derived, vitamin D-regulating hormone, fibroblast growth factor 23 (FGF23), are prospectively associated with death in critically ill patients with AKI requiring RRT, and in a general cohort of critically ill patients with and without AKI. Design, setting, participants, & measurements We measured plasma FGF23 and other mineral metabolite levels in two cohorts of critically ill patients (n=1527). We included 817 patients with AKI requiring RRT who enrolled in the ARF Trial Network (ATN) study, and 710 patients with and without AKI who enrolled in the Validating Acute Lung Injury biomarkers for Diagnosis (VALID) study. We hypothesized that higher FGF23 levels at enrollment are independently associated with higher 60-day mortality. Results In the ATN study, patients in the highest compared with lowest quartiles of C-terminal (cFGF23) and intact FGF23 (iFGF23) had 3.84 (95% confidence interval, 2.31 to 6.41) and 2.08 (95% confidence interval, 1.03 to 4.21) fold higher odds of death, respectively, after adjustment for demographics, comorbidities, and severity of illness. In contrast, plasma/serum levels of parathyroid hormone, vitamin D metabolites, calcium, and phosphate were not associated with 60-day mortality. In the VALID study, patients in the highest compared with lowest quartiles of cFGF23 and iFGF23 had 3.52 (95% confidence interval, 1.96 to 6.33) and 1.93 (95% confidence interval, 1.12 to 3.33) fold higher adjusted odds of death. Conclusions Higher FGF23 levels are independently associated with greater mortality in critically ill patients.This publication has 49 references indexed in Scilit:
- Serum 1,25-Dihydroxyvitamin D: An Outcome Prognosticator in Human SepsisPLOS ONE, 2013
- FGF23 neutralization improves chronic kidney disease–associated hyperparathyroidism yet increases mortalityJCI Insight, 2012
- Fibroblast Growth Factor 23 and Risks of Mortality and End-Stage Renal Disease in Patients With Chronic Kidney DiseaseJAMA, 2011
- Association of low serum 25-hydroxyvitamin D levels and mortality in the critically ill*Critical Care Medicine, 2011
- Direct evidence for a causative role of FGF23 in the abnormal renal phosphate handling and vitamin D metabolism in rats with early-stage chronic kidney diseaseKidney International, 2010
- Isolated C-terminal tail of FGF23 alleviates hypophosphatemia by inhibiting FGF23-FGFR-Klotho complex formationProceedings of the National Academy of Sciences of the United States of America, 2009
- Fibroblast Growth Factor 23 and Mortality among Patients Undergoing HemodialysisThe New England Journal of Medicine, 2008
- Intensity of Renal Support in Critically Ill Patients with Acute Kidney InjuryThe New England Journal of Medicine, 2008
- APACHE II-A Severity of Disease Classification SystemCritical Care Medicine, 1986
- APACHE IICritical Care Medicine, 1985