Fibroblast growth factor 23 associates with death in critically ill patients

David E. Leaf*, Edward D. Siew, Michele F. Eisenga, Karandeep Singh, Finnian R. Mc Causland, Anand Srivastava, T. Alp Ikizler, Lorraine B. Ware, Adit A. Ginde, John A. Kellum, Paul M. Palevsky, Myles Wolf, Sushrut S. Waikar

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)531-541
Number of pages11
JournalClinical Journal of the American Society of Nephrology
Issue number4
StatePublished - Apr 6 2018


  • Acute kidney injury
  • Acute lung injury
  • Acute renal failure
  • Biomarkers
  • Calcium, dietary
  • Cohort studies
  • Comorbidity
  • Confidence intervals
  • Critical illness
  • Demography
  • Fibroblast growth factor 23
  • Fibroblast growth factors
  • Humans
  • Minerals
  • Osteocytes
  • Parathyroid hormone
  • Phosphates
  • Renal dialysis
  • Renal replacement therapy
  • Vitamin D

ASJC Scopus subject areas

  • Epidemiology
  • Critical Care and Intensive Care Medicine
  • Nephrology
  • Transplantation

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