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

Onn Shaun Thein; Naeman Akbar Ali; Rahul Y Mahida; Rachel C A Dancer; Marlies Ostermann; Karin Amrein; Gennaro Martucci; Aaron Scott; David R Thickett; Dhruv Parekh

doi:10.3390/biology12020309

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

Onn Shaun Thein, Naeman Akbar Ali, Rahul Y Mahida, Rachel C A Dancer, Marlies Ostermann, Karin Amrein, Gennaro Martucci, Aaron Scott, David R Thickett, Dhruv Parekh

Inflammation and Ageing

Research output: Contribution to journal › Article › peer-review

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Abstract

BACKGROUND: 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.

METHODS: Plasma FGF23 levels were measured by ELISA in two separate cohorts of patients receiving vitamin D supplementation: critical illness patients (VITdAL-ICU trial, n = 475) and elective oesophagectomy patients (VINDALOO trial, n = 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 ( n = 27).

RESULTS: Elevated FGF23 (quartile 4 vs. quartiles 1-3) was associated with increased short-term (30 and 180 day) mortality in critical illness patients ( p < 0.001) and long-term (two-year) mortality in oesophagectomy patients ( p = 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) ( p = 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) ( p < 0.001). This was found to be independent of vitamin D or CKD status (critical illness p = 0.3507; oesophagectomy p = 0.3800). FGF23 levels in healthy controls were similar to those seen in oesophagectomy patients ( p = 0.4802).

CONCLUSIONS: 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.

Original language	English
Article number	309
Number of pages	12
Journal	Biology
Volume	12
Issue number	2
DOIs	https://doi.org/10.3390/biology12020309
Publication status	Published - 14 Feb 2023

Bibliographical note

Funding:
OST/DT/DP: Birmingham Health Partners, NA/AS/DT/DP: Chernakovsky Foundation, DT/DP: Health Technology Assessment (NIHR17/147/33), DT/AS/DP: Health Technology Assessment (NIHR129593), AS/DT/DP: Efficacy and Mechanism Evaluation (NIHR131600), AS/DT: Asthma + Lung UK (MCFPHD20F\2), DT/AS: Medical Research Council (MR/S002782/1; MR/J011266/1; G1100196), RYM: Medical Research Council (MR/X000338/1), KA: Fresenius Kabi (Germany), and the Austrian National Bank (Jubiläumsfonds, Project Nr. 14143).

Keywords

FGF23
critical illness
intensive care

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TheinO2023RaisedFinal published version, 1.17 MBLicence: Creative Commons: Attribution (CC BY)

2 Finished
4 Active

Efficacy and Mechanism Evaluation -Effectiveness of Electronic Cigarettes compared with varenicline for smoking cessation in patients with COPD and effect on the Lungs (EME-ECAL study)
Scott, A., Sapey, E., Handley, K., Thickett, D., Parekh, D. & Farley, A.
NIHR
1/03/23 → 28/02/26
Project: Other Government Departments
Extracellular vesicles and their cargo in the pathogenesis of acute respiratory distress syndrome and pulmonary fibrosis sequelae
Scott, A., Mahida, R., Parekh, D. & Thickett, D.
Medical Research Council
1/10/22 → 30/09/27
Project: Research Councils
Effectiveness of Electronic Cigarettes compared with combination nicotine replacement therapy for smoking cessation in patients with chronic obstructive pulmonary disease and effect on Lung health (ECAL study).
Scott, A., Handley, K., Sapey, E., Adab, P., Jowett, S., Farley, A., Jordan, R., Parekh, D. & Thickett, D.
NIHR
1/09/22 → 30/09/25
Project: Other Government Departments
Evaluating the impact of E-cigarettes on the innate immune response in chronic obstructive pulmonary disease
Sapey, E., Thickett, D. & Scott, A.
BRITISH LUNG FOUNDATION
1/10/21 → 30/09/24
Project: Research
Does hospitalisation of older patients with severe community acquired pneumonia and sepsis lead to long term
Sapey, E., Thickett, D., Richter, A., Patel, J., Mitchell, T. & Scott, A.
Medical Research Council
1/07/19 → 30/06/23
Project: Research Councils
Development Clinical Studies - development of Vitamin D therapy to prevent acute lung injury
Thickett, D.
Medical Research Council
1/01/12 → 31/03/15
Project: Research Councils

Cite this

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

abstract = "BACKGROUND: 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.METHODS: Plasma FGF23 levels were measured by ELISA in two separate cohorts of patients receiving vitamin D supplementation: critical illness patients (VITdAL-ICU trial, n = 475) and elective oesophagectomy patients (VINDALOO trial, n = 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 ( n = 27). RESULTS: Elevated FGF23 (quartile 4 vs. quartiles 1-3) was associated with increased short-term (30 and 180 day) mortality in critical illness patients ( p < 0.001) and long-term (two-year) mortality in oesophagectomy patients ( p = 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) ( p = 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) ( p < 0.001). This was found to be independent of vitamin D or CKD status (critical illness p = 0.3507; oesophagectomy p = 0.3800). FGF23 levels in healthy controls were similar to those seen in oesophagectomy patients ( p = 0.4802). CONCLUSIONS: 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.",

keywords = "FGF23, critical illness, intensive care",

author = "Thein, {Onn Shaun} and Ali, {Naeman Akbar} and Mahida, {Rahul Y} and Dancer, {Rachel C A} and Marlies Ostermann and Karin Amrein and Gennaro Martucci and Aaron Scott and Thickett, {David R} and Dhruv Parekh",

note = "Funding: OST/DT/DP: Birmingham Health Partners, NA/AS/DT/DP: Chernakovsky Foundation, DT/DP: Health Technology Assessment (NIHR17/147/33), DT/AS/DP: Health Technology Assessment (NIHR129593), AS/DT/DP: Efficacy and Mechanism Evaluation (NIHR131600), AS/DT: Asthma + Lung UK (MCFPHD20F\2), DT/AS: Medical Research Council (MR/S002782/1; MR/J011266/1; G1100196), RYM: Medical Research Council (MR/X000338/1), KA: Fresenius Kabi (Germany), and the Austrian National Bank (Jubil{\"a}umsfonds, Project Nr. 14143).",

year = "2023",

month = feb,

day = "14",

doi = "10.3390/biology12020309",

language = "English",

volume = "12",

journal = "Biology",

issn = "2079-7737",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

number = "2",

}

TY - JOUR

T1 - Raised FGF23 Correlates to Increased Mortality in Critical Illness, Independent of Vitamin D

AU - Thein, Onn Shaun

AU - Ali, Naeman Akbar

AU - Mahida, Rahul Y

AU - Dancer, Rachel C A

AU - Ostermann, Marlies

AU - Amrein, Karin

AU - Martucci, Gennaro

AU - Scott, Aaron

AU - Thickett, David R

AU - Parekh, Dhruv

N1 - Funding: OST/DT/DP: Birmingham Health Partners, NA/AS/DT/DP: Chernakovsky Foundation, DT/DP: Health Technology Assessment (NIHR17/147/33), DT/AS/DP: Health Technology Assessment (NIHR129593), AS/DT/DP: Efficacy and Mechanism Evaluation (NIHR131600), AS/DT: Asthma + Lung UK (MCFPHD20F\2), DT/AS: Medical Research Council (MR/S002782/1; MR/J011266/1; G1100196), RYM: Medical Research Council (MR/X000338/1), KA: Fresenius Kabi (Germany), and the Austrian National Bank (Jubiläumsfonds, Project Nr. 14143).

PY - 2023/2/14

Y1 - 2023/2/14

N2 - BACKGROUND: 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.METHODS: Plasma FGF23 levels were measured by ELISA in two separate cohorts of patients receiving vitamin D supplementation: critical illness patients (VITdAL-ICU trial, n = 475) and elective oesophagectomy patients (VINDALOO trial, n = 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 ( n = 27). RESULTS: Elevated FGF23 (quartile 4 vs. quartiles 1-3) was associated with increased short-term (30 and 180 day) mortality in critical illness patients ( p < 0.001) and long-term (two-year) mortality in oesophagectomy patients ( p = 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) ( p = 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) ( p < 0.001). This was found to be independent of vitamin D or CKD status (critical illness p = 0.3507; oesophagectomy p = 0.3800). FGF23 levels in healthy controls were similar to those seen in oesophagectomy patients ( p = 0.4802). CONCLUSIONS: 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.

AB - BACKGROUND: 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.METHODS: Plasma FGF23 levels were measured by ELISA in two separate cohorts of patients receiving vitamin D supplementation: critical illness patients (VITdAL-ICU trial, n = 475) and elective oesophagectomy patients (VINDALOO trial, n = 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 ( n = 27). RESULTS: Elevated FGF23 (quartile 4 vs. quartiles 1-3) was associated with increased short-term (30 and 180 day) mortality in critical illness patients ( p < 0.001) and long-term (two-year) mortality in oesophagectomy patients ( p = 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) ( p = 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) ( p < 0.001). This was found to be independent of vitamin D or CKD status (critical illness p = 0.3507; oesophagectomy p = 0.3800). FGF23 levels in healthy controls were similar to those seen in oesophagectomy patients ( p = 0.4802). CONCLUSIONS: 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.

KW - FGF23

KW - critical illness

KW - intensive care

U2 - 10.3390/biology12020309

DO - 10.3390/biology12020309

M3 - Article

C2 - 36829583

SN - 2079-7737

VL - 12

JO - Biology

JF - Biology

IS - 2

M1 - 309

ER -

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

Abstract

Bibliographical note

Keywords

Access to Document

Fingerprint

Projects

Efficacy and Mechanism Evaluation -Effectiveness of Electronic Cigarettes compared with varenicline for smoking cessation in patients with COPD and effect on the Lungs (EME-ECAL study)

Extracellular vesicles and their cargo in the pathogenesis of acute respiratory distress syndrome and pulmonary fibrosis sequelae

Effectiveness of Electronic Cigarettes compared with combination nicotine replacement therapy for smoking cessation in patients with chronic obstructive pulmonary disease and effect on Lung health (ECAL study).

Evaluating the impact of E-cigarettes on the innate immune response in chronic obstructive pulmonary disease

Does hospitalisation of older patients with severe community acquired pneumonia and sepsis lead to long term

Development Clinical Studies - development of Vitamin D therapy to prevent acute lung injury

Cite this