Fibroblast growth factor 21 and protein energy wasting in hemodialysis patients

Adrian Post; Dion Groothof; Joëlle C Schutten; Dylan Kelly; J Casper Swarte; Jose L Flores-Guerrero; Yvonne van der Veen; Ido P Kema; Akin Ozyilmaz; Ayano Enya; Ralf Westerhuis; Stephan J L Bakker; Casper F M Franssen

doi:10.1016/j.clnu.2021.01.036

Fibroblast growth factor 21 and protein energy wasting in hemodialysis patients

Adrian Post^*, Dion Groothof, Joëlle C Schutten, Dylan Kelly, J Casper Swarte, Jose L Flores-Guerrero, Yvonne van der Veen, Ido P Kema, Akin Ozyilmaz, Ayano Enya, Ralf Westerhuis, Stephan J L Bakker, Casper F M Franssen

^*Corresponding author for this work

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

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Abstract

INTRODUCTION: Protein energy wasting (PEW) is the most important risk factor for morbidity and mortality in hemodialysis patients. Inadequate dietary protein intake is a frequent cause of PEW. Recent studies have identified fibroblast growth factor 21 (FGF21) as an endocrine protein sensor. This study aims to investigate the potential of FGF21 as a biomarker for protein intake and PEW and to investigate intradialytic FGF21 changes.

METHODS: Plasma FGF21 was measured using an enzyme-linked immunoassay. Complete intradialytic dialysate and interdialytic urinary collections were used to calculate 24-h urea excretion and protein intake. Muscle mass was assessed using the creatinine excretion rate and fatigue was assessed using the Short Form 36 and the Checklist Individual Strength.

RESULTS: Out of 59 hemodialysis patients (65 ± 15 years, 63% male), 39 patients had a low protein intake, defined as a protein intake less than 0.9 g/kg/24-h. Patients with a low protein intake had nearly twofold higher plasma FGF21 compared to those with an adequate protein intake (FGF21 1370 [795-4034] pg/mL versus 709 [405-1077] pg/mL;P < 0.001). Higher plasma FGF21 was associated with higher odds of low protein intake (Odds Ratio: 3.18 [1.62-7.95] per doubling of FGF21; P = 0.004), independent of potential confounders. Higher plasma FGF21 was also associated with lower muscle mass (std β: -0.34 [-0.59;-0.09];P = 0.009), lower vitality (std β: -0.30 [-0.55;-0.05];P = 0.02), and more fatigue (std β: 0.32 [0.07;0.57];P = 0.01). During hemodialysis plasma FGF21 increased by 354 [71-570] pg/mL, corresponding to a 29% increase.

CONCLUSION: Higher plasma FGF21 is associated with higher odds of low protein intake in hemodialysis patients. Secondarily, plasma FGF21 is also associated with lower muscle mass, less vitality, and more fatigue. Lastly, there is an intradialytic increase in plasma FGF21. FGF21 could be a valuable marker allowing for objective assessment of PEW.

Original language	English
Pages (from-to)	4216-4224
Number of pages	9
Journal	Clinical Nutrition
Volume	40
Issue number	6
Early online date	3-Feb-2021
DOIs	https://doi.org/10.1016/j.clnu.2021.01.036
Publication status	Published - Jun-2021

Keywords

FGF21
Protein intake
Protein energy wasting
Muscle mass
Fatigue
Hemodialysis
URINARY CREATININE EXCRETION
SKELETAL-MUSCLE MASS
BODY-COMPOSITION
NUTRITION
FATIGUE
MALNUTRITION
DIALYSIS
SF-36

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Post, A., Groothof, D., Schutten, J. C., Kelly, D., Swarte, J. C., Flores-Guerrero, J. L., van der Veen, Y., Kema, I. P., Ozyilmaz, A., Enya, A., Westerhuis, R., Bakker, S. J. L., & Franssen, C. F. M. (2021). Fibroblast growth factor 21 and protein energy wasting in hemodialysis patients. Clinical Nutrition, 40(6), 4216-4224. https://doi.org/10.1016/j.clnu.2021.01.036

@article{5e0bfb71644f48378fd4d8f263ec998a,

title = "Fibroblast growth factor 21 and protein energy wasting in hemodialysis patients",

abstract = "INTRODUCTION: Protein energy wasting (PEW) is the most important risk factor for morbidity and mortality in hemodialysis patients. Inadequate dietary protein intake is a frequent cause of PEW. Recent studies have identified fibroblast growth factor 21 (FGF21) as an endocrine protein sensor. This study aims to investigate the potential of FGF21 as a biomarker for protein intake and PEW and to investigate intradialytic FGF21 changes.METHODS: Plasma FGF21 was measured using an enzyme-linked immunoassay. Complete intradialytic dialysate and interdialytic urinary collections were used to calculate 24-h urea excretion and protein intake. Muscle mass was assessed using the creatinine excretion rate and fatigue was assessed using the Short Form 36 and the Checklist Individual Strength.RESULTS: Out of 59 hemodialysis patients (65 ± 15 years, 63% male), 39 patients had a low protein intake, defined as a protein intake less than 0.9 g/kg/24-h. Patients with a low protein intake had nearly twofold higher plasma FGF21 compared to those with an adequate protein intake (FGF21 1370 [795-4034] pg/mL versus 709 [405-1077] pg/mL;P < 0.001). Higher plasma FGF21 was associated with higher odds of low protein intake (Odds Ratio: 3.18 [1.62-7.95] per doubling of FGF21; P = 0.004), independent of potential confounders. Higher plasma FGF21 was also associated with lower muscle mass (std β: -0.34 [-0.59;-0.09];P = 0.009), lower vitality (std β: -0.30 [-0.55;-0.05];P = 0.02), and more fatigue (std β: 0.32 [0.07;0.57];P = 0.01). During hemodialysis plasma FGF21 increased by 354 [71-570] pg/mL, corresponding to a 29% increase.CONCLUSION: Higher plasma FGF21 is associated with higher odds of low protein intake in hemodialysis patients. Secondarily, plasma FGF21 is also associated with lower muscle mass, less vitality, and more fatigue. Lastly, there is an intradialytic increase in plasma FGF21. FGF21 could be a valuable marker allowing for objective assessment of PEW.",

keywords = "FGF21, Protein intake, Protein energy wasting, Muscle mass, Fatigue, Hemodialysis, URINARY CREATININE EXCRETION, SKELETAL-MUSCLE MASS, BODY-COMPOSITION, NUTRITION, FATIGUE, MALNUTRITION, DIALYSIS, SF-36",

author = "Adrian Post and Dion Groothof and Schutten, {Jo{\"e}lle C} and Dylan Kelly and Swarte, {J Casper} and Flores-Guerrero, {Jose L} and {van der Veen}, Yvonne and Kema, {Ido P} and Akin Ozyilmaz and Ayano Enya and Ralf Westerhuis and Bakker, {Stephan J L} and Franssen, {Casper F M}",

year = "2021",

month = jun,

doi = "10.1016/j.clnu.2021.01.036",

language = "English",

volume = "40",

pages = "4216--4224",

journal = "Clinical Nutrition",

issn = "0261-5614",

publisher = "Churchill Livingstone",

number = "6",

}

TY - JOUR

T1 - Fibroblast growth factor 21 and protein energy wasting in hemodialysis patients

AU - Post, Adrian

AU - Groothof, Dion

AU - Schutten, Joëlle C

AU - Kelly, Dylan

AU - Swarte, J Casper

AU - Flores-Guerrero, Jose L

AU - van der Veen, Yvonne

AU - Kema, Ido P

AU - Ozyilmaz, Akin

AU - Enya, Ayano

AU - Westerhuis, Ralf

AU - Bakker, Stephan J L

AU - Franssen, Casper F M

PY - 2021/6

Y1 - 2021/6

N2 - INTRODUCTION: Protein energy wasting (PEW) is the most important risk factor for morbidity and mortality in hemodialysis patients. Inadequate dietary protein intake is a frequent cause of PEW. Recent studies have identified fibroblast growth factor 21 (FGF21) as an endocrine protein sensor. This study aims to investigate the potential of FGF21 as a biomarker for protein intake and PEW and to investigate intradialytic FGF21 changes.METHODS: Plasma FGF21 was measured using an enzyme-linked immunoassay. Complete intradialytic dialysate and interdialytic urinary collections were used to calculate 24-h urea excretion and protein intake. Muscle mass was assessed using the creatinine excretion rate and fatigue was assessed using the Short Form 36 and the Checklist Individual Strength.RESULTS: Out of 59 hemodialysis patients (65 ± 15 years, 63% male), 39 patients had a low protein intake, defined as a protein intake less than 0.9 g/kg/24-h. Patients with a low protein intake had nearly twofold higher plasma FGF21 compared to those with an adequate protein intake (FGF21 1370 [795-4034] pg/mL versus 709 [405-1077] pg/mL;P < 0.001). Higher plasma FGF21 was associated with higher odds of low protein intake (Odds Ratio: 3.18 [1.62-7.95] per doubling of FGF21; P = 0.004), independent of potential confounders. Higher plasma FGF21 was also associated with lower muscle mass (std β: -0.34 [-0.59;-0.09];P = 0.009), lower vitality (std β: -0.30 [-0.55;-0.05];P = 0.02), and more fatigue (std β: 0.32 [0.07;0.57];P = 0.01). During hemodialysis plasma FGF21 increased by 354 [71-570] pg/mL, corresponding to a 29% increase.CONCLUSION: Higher plasma FGF21 is associated with higher odds of low protein intake in hemodialysis patients. Secondarily, plasma FGF21 is also associated with lower muscle mass, less vitality, and more fatigue. Lastly, there is an intradialytic increase in plasma FGF21. FGF21 could be a valuable marker allowing for objective assessment of PEW.

AB - INTRODUCTION: Protein energy wasting (PEW) is the most important risk factor for morbidity and mortality in hemodialysis patients. Inadequate dietary protein intake is a frequent cause of PEW. Recent studies have identified fibroblast growth factor 21 (FGF21) as an endocrine protein sensor. This study aims to investigate the potential of FGF21 as a biomarker for protein intake and PEW and to investigate intradialytic FGF21 changes.METHODS: Plasma FGF21 was measured using an enzyme-linked immunoassay. Complete intradialytic dialysate and interdialytic urinary collections were used to calculate 24-h urea excretion and protein intake. Muscle mass was assessed using the creatinine excretion rate and fatigue was assessed using the Short Form 36 and the Checklist Individual Strength.RESULTS: Out of 59 hemodialysis patients (65 ± 15 years, 63% male), 39 patients had a low protein intake, defined as a protein intake less than 0.9 g/kg/24-h. Patients with a low protein intake had nearly twofold higher plasma FGF21 compared to those with an adequate protein intake (FGF21 1370 [795-4034] pg/mL versus 709 [405-1077] pg/mL;P < 0.001). Higher plasma FGF21 was associated with higher odds of low protein intake (Odds Ratio: 3.18 [1.62-7.95] per doubling of FGF21; P = 0.004), independent of potential confounders. Higher plasma FGF21 was also associated with lower muscle mass (std β: -0.34 [-0.59;-0.09];P = 0.009), lower vitality (std β: -0.30 [-0.55;-0.05];P = 0.02), and more fatigue (std β: 0.32 [0.07;0.57];P = 0.01). During hemodialysis plasma FGF21 increased by 354 [71-570] pg/mL, corresponding to a 29% increase.CONCLUSION: Higher plasma FGF21 is associated with higher odds of low protein intake in hemodialysis patients. Secondarily, plasma FGF21 is also associated with lower muscle mass, less vitality, and more fatigue. Lastly, there is an intradialytic increase in plasma FGF21. FGF21 could be a valuable marker allowing for objective assessment of PEW.

KW - FGF21

KW - Protein intake

KW - Protein energy wasting

KW - Muscle mass

KW - Fatigue

KW - Hemodialysis

KW - URINARY CREATININE EXCRETION

KW - SKELETAL-MUSCLE MASS

KW - BODY-COMPOSITION

KW - NUTRITION

KW - FATIGUE

KW - MALNUTRITION

KW - DIALYSIS

KW - SF-36

U2 - 10.1016/j.clnu.2021.01.036

DO - 10.1016/j.clnu.2021.01.036

M3 - Article

C2 - 33589239

SN - 0261-5614

VL - 40

SP - 4216

EP - 4224

JO - Clinical Nutrition

JF - Clinical Nutrition

IS - 6

ER -

Fibroblast growth factor 21 and protein energy wasting in hemodialysis patients

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