Association between circulating fibroblast growth factor 21 and mortality in end-stage renal disease

Kohara, Marina; Masuda, Tomoyuki; Shiizaki, Kazuhiro; Akimoto, Tetsu; Watanabe, Yuko; Honma, Sato; Sekiguchi, Chuji; Miyazawa, Yasuharu; Kusano, Eiji; Kanda, Yoshinobu; Asano, Yoshihide; Kuro‐o, Makoto; Nagata, Daisuke

doi:10.1371/journal.pone.0178971

Cited by 59 publications

(56 citation statements)

References 44 publications

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“…After dialysis initiation, creatinine and GFR no longer correlate independently with circulating levels of FGF21, and it is possible that other non-renal factors could play the major role [3, 15]. …”

Section: Fgf21 Levels and Sources In Ckdmentioning

confidence: 99%

“…Uremic toxins, metabolic acidosis, anemia and hyperphosphatemia may also contribute to FGF21 elevation [3, 48]. CKD-related factors could elevate circulating FGF21 levels because CKD represents a systemic or cellular metabolic stress, or CKD may cause FGF21 resistance in target organs [42, 49] as a result of downregulation of β-klotho or FGFR1c expression in target tissues.…”

Section: Fgf21 Levels and Sources In Ckdmentioning

confidence: 99%

“…However, these correlations seem to depend on the diabetic state and CKD stage. Similarly, FGF21 serum levels correlate positively with inflammatory markers such as IL-6, hrCRP, β-microglobulin and fibrinogen [2, 3, 15, 44, 45, 103–105]. …”

Section: Fgf21 In Human Ckd: Observational Datamentioning

confidence: 99%

“…A higher overall mortality was observed in the high-FGF21 group, but a higher incidence of cardiovascu- lar events was not observed. In a multivariate and adjusted analysis, elevated FGF21 levels were shown to be an independent predictor of all-cause mortality in this population [3]. One fact about all these observational studies is that only the total levels of FGF21 were measured by the ELISA technique.…”

Section: Fgf21 In Human Ckd: Observational Datamentioning

confidence: 99%

“…Currently, there are observational studies with CKD patients showing interesting correlations, but the mechanisms of, reasons for, and functional sequelae of FGF21 elevation in CKD remain elusive. There is a positive correlation of FGF21 level with mortality in dialysis patients [3]. In type 2 diabetic (T2D) patients, serum FGF21 levels correlate with nephropathy onset, albuminuria, and risk of progression to end-stage renal disease (ESRD) [4–6].…”

Section: Introductionmentioning

confidence: 99%

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Fibroblast growth factor 21 in chronic kidney disease

et al. 2018

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Fibroblast growth factor 21 (FGF21) is a member of the endocrine FGF family that acts as a metabolic regulator of both glucose and lipid metabolism. Similar to fibroblast growth factor 23 (FGF23), serum FGF21 levels rise progressively with the loss of renal function, reaching 20 times normal values in end-stage renal disease. In patients with chronic kidney disease (CKD), higher serum FGF21 levels correlate with poorer metabolic profile, higher inflammatory markers, more comorbidities, and higher mortality. The high serum FGF21 levels are above and beyond what can be explained by the loss of FGF21 renal clearance, suggesting increased production and/or impaired non-renal clearance. In diabetic nephropathy, serum FGF21 levels correlate with the severity of albuminuria and faster loss of glomerular filtrate rate and can potentially be a biomarker of poor prognostic. The observational and associative human data contrast sharply with in vitro and in vivo preclinical experimental data, which is more in line with a protective role of FGF21 in chronic nephropathies. We here review the physiology of FGF21, and the literature regarding its behavior in CKD with particular focus on diabetic nephropathy. Finally, we speculate on the role of FGF21 in CKD.

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Section: Fgf21 Levels and Sources In Ckdmentioning

confidence: 99%

Section: Fgf21 Levels and Sources In Ckdmentioning

confidence: 99%

Section: Fgf21 In Human Ckd: Observational Datamentioning

confidence: 99%

Section: Fgf21 In Human Ckd: Observational Datamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Fibroblast growth factor 21 in chronic kidney disease

et al. 2018

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Fibroblast growth factor 21 in patients with cardiac cachexia: a possible role of chronic inflammation

et al. 2019

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AimsCardiac cachexia is a wasting syndrome characterized by chronic inflammation and high mortality. Fibroblast growth factor 21 (FGF‐21) and monocyte chemoattractant protein 1 (MCP‐1) are associated with cardiovascular disease and systemic inflammation. We investigated FGF‐21 and MCP‐1 in relations to cardiac function, inflammation, and wasting in patients with heart failure with reduced ejection fraction (HFrEF) and cardiac cachexia.Methods and resultsPlasma FGF‐21 and MCP‐1 were measured in a cross‐sectional study among the three study groups: 19 patients with HFrEF with cardiac cachexia, 19 patients with HFrEF without cachexia, and 19 patients with ischaemic heart disease and preserved ejection fraction. Patients with HFrEF and cardiac cachexia displayed higher FGF‐21 levels median (inter quantile range) 381 (232–577) pg/mL than patients with HFrEF without cachexia 224 (179–309) pg/mL and ischaemic heart disease patients 221 (156–308) pg/mL (P = 0.0496). No difference in MCP‐1 levels were found among the groups (P = 0.345). In a multivariable regression analysis, FGF‐21 (logarithm 2) was independently associated with interleukin 6 (logarithm 2) (P = 0.015) and lower muscle mass (P = 0.043), while no relation with N‐terminal pro‐hormone brain natriuretic peptide was observed.ConclusionsFibroblast growth factor 21 (FGF‐21) levels were elevated in patients with HFrEF and cardiac cachexia, which could be mediated by increased inflammation and muscle wasting rather than impaired cardiac function.

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Pro‐Inflammatory Proteins Associated with Frailty and Its Progression—A Longitudinal Study in Community‐Dwelling Women

Mitchell

Malmgren

Bartosch

et al. 2023

J of Bone & Mineral Res

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The complex pathophysiology underlying biological aging creates challenges for identifying biomarkers associated with frailty. This longitudinal, nontargeted proteomics study aimed to identify proteins associated with frailty, particularly the change from nonfrail to frail. The population‐based Osteoporosis Prospective Risk Assessment cohort includes women all of whom are 75 years old at inclusion (n = 1044) and reassessed at 80 years (n = 715) and 85 years (n = 382). A deficits in health frailty index (FI) and 92 plasma proteins (Olink CVD‐II panel) were available at all ages. The identical age facilitated differentiating chronological and biological aging. Bidirectional analyses, performed cross‐sectionally and longitudinally, used regression models controlled for false discovery rate (FDR), across 5‐ and 10‐year time windows and longitudinal mixed models. Frailty outcomes were frailty index, frailty status (frail defined as FI ≥ 0.25), change in frailty index, and change in frailty status, together with protein expression or change in protein expression. Elevated levels of 32 proteins were positively associated with the FI, cross‐sectionally at all ages (range: β‐coefficients 0.22–2.06; FDR 0.021–0.024), of which 18 were also associated with frailty status (range: odds ratios 1.40–5.77; FDR 0.022–0.016). Based on the accrued data, eight core proteins (CD4, FGF23, Gal‐9, PAR‐1, REN, TNFRSF10A TNFRSF11A, and TNFRSF10B) are proposed. A one‐unit change in the FI was additively associated with increased protein expression over 5 and 10 years (range: β‐coefficients 0.52–1.59; p < 0.001). Increments in baseline FI consistently associated with a change in protein expression over time (5 years, β‐range 0.05–1.35; 10 years, β‐range 0.51–1.48; all p < 0.001). A one‐unit increase in protein expression was also associated with an increased probability of being frail (FI ≥ 0.25) (β‐range: 0.14–0.61). Mirroring the multisystem deterioration that typifies frailty, the proteins and their associated biological pathways reflect pathologies, including the renal system, skeletal homeostasis, and TRAIL‐activated apoptotic signaling. The core proteins are compelling candidates for understanding the development and progression of frailty with advancing age, including the intrinsic musculoskeletal component. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

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Association between circulating fibroblast growth factor 21 and mortality in end-stage renal disease

Cited by 59 publications

References 44 publications

Fibroblast growth factor 21 in chronic kidney disease

Fibroblast growth factor 21 in chronic kidney disease

Fibroblast growth factor 21 in patients with cardiac cachexia: a possible role of chronic inflammation

Pro‐Inflammatory Proteins Associated with Frailty and Its Progression—A Longitudinal Study in Community‐Dwelling Women

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