Raised FGF23 Correlates to Increased Mortality in Critical Illness, Independent of Vitamin D

• Published in: Biology (Basel, Switzerland) Vol. 12; no. 2; p. 309
• Main Authors: Thein, Onn Shaun, Ali, Naeman Akbar, Mahida, Rahul Y, Dancer, Rachel C A, Ostermann, Marlies, Amrein, Karin, Martucci, Gennaro, Scott, Aaron, Thickett, David R, Parekh, Dhruv
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14-02-2023; MDPI
• Subjects: Age; Alfacalcidol; Breastfeeding & lactation; Calcifediol; Calcium phosphates; Chronic kidney failure; Clinical trials; Critical care; critical illness; Cytokines; Dietary supplements; Enzyme-linked immunosorbent assay; FGF23; Fibroblast growth factor 23; Fibroblast growth factors; Health aspects; Homeostasis; Illnesses; Immune system; intensive care; Kidney diseases; Kidney stones; Medical research; Medicine, Experimental; Mortality; Patients; Phosphates; Pneumonia; Primidone; Risk factors; Sarcoidosis; Sepsis; Statistical analysis; Statistical significance; United Kingdom; Vitamin D; Vitamin deficiency; United Kingdom; United Kingdom > UK; Austria; intensive care; critical illness; FGF23
• ISSN: 2079-7737; 2079-7737
• DOI: 10.3390/biology12020309

Fibroblast Growth Factor (FGF23) is an endocrine hormone classically associated with the homeostasis of vitamin D, phosphate, and calcium. Elevated serum FGF23 is a known independent risk factor for mortality in chronic kidney disease (CKD) patients. We aimed to determine if there was a similar relationship between FGF23 levels and mortality in critically ill patients.
Plasma FGF23 levels were measured by ELISA in two separate cohorts of patients receiving vitamin D supplementation: critical illness patients (VITdAL-ICU trial,
= 475) and elective oesophagectomy patients (VINDALOO trial,
= 76). Mortality data were recorded at 30 and 180 days or at two years, respectively. FGF23 levels in a healthy control cohort were also measured (
= 27).
Elevated FGF23 (quartile 4 vs. quartiles 1-3) was associated with increased short-term (30 and 180 day) mortality in critical illness patients (
< 0.001) and long-term (two-year) mortality in oesophagectomy patients (
= 0.0149). Patients who died had significantly higher FGF23 levels than those who survived: In the critical illness cohort, those who died had 1194.6 pg/mL (range 0-14,000), while those who survived had 120.4 pg/mL (range = 15-14,000) (
= 0.0462). In the oesophagectomy cohort, those who died had 1304 pg/mL (range = 154-77,800), while those who survived had 644 pg/mL (range = 179-54,894) (
< 0.001). This was found to be independent of vitamin D or CKD status (critical illness
= 0.3507; oesophagectomy
= 0.3800). FGF23 levels in healthy controls were similar to those seen in oesophagectomy patients (
= 0.4802).
Elevated baseline serum FGF23 is correlated with increased mortality in both the post-oesophagectomy cohort and the cohort of patients with critical illness requiring intensive care admission. This was independent of vitamin D status, supplementation, or CKD status, which suggests the presence of vitamin D-independent mechanisms of FGF23 action during the acute and convalescent stages of critical illness, warranting further investigation.