Tumor necrosis factor stimulates fibroblast growth factor 23 levels in chronic kidney disease and non-renal inflammation.

Egli-Spichtig, Daniela; Imenez Silva, Pedro Henrique; Glaudemans, Bob; Gehring, Nicole; Bettoni, Carla; Zhang, Martin Y H; Pastor-Arroyo, Eva M; Schönenberger, Désirée; Rajski, Michal; Hoogewijs, David; Knauf, Felix; Misselwitz, Benjamin; Frey-Wagner, Isabelle; Rogler, Gerhard; Ackermann, Daniel; Ponte, Belen; Pruijm, Menno; Leichtle, Alexander; Fiedler, Georg-Martin; Bochud, Murielle; ... (2019). Tumor necrosis factor stimulates fibroblast growth factor 23 levels in chronic kidney disease and non-renal inflammation. Kidney international, 96(4), pp. 890-905. Elsevier 10.1016/j.kint.2019.04.009

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Fibroblast growth factor 23 (FGF23) regulates phosphate homeostasis, and its early rise in patients with chronic kidney disease is independently associated with all-cause mortality. Since inflammation is characteristic of chronic kidney disease and associates with increased plasma FGF23 we examined whether inflammation directly stimulates FGF23. In a population-based cohort, plasma tumor necrosis factor (TNF) was the only inflammatory cytokine that independently and positively correlated with plasma FGF23. Mouse models of chronic kidney disease showed signs of renal inflammation, renal FGF23 expression and elevated systemic FGF23 levels. Renal FGF23 expression coincided with expression of the orphan nuclear receptor Nurr1 regulating FGF23 in other organs. Antibody-mediated neutralization of TNF normalized plasma FGF23 and suppressed ectopic renal Fgf23 expression. Conversely, TNF administration to control mice increased plasma FGF23 without altering plasma phosphate. Moreover, in Il10-deficient mice with inflammatory bowel disease and normal kidney function, plasma FGF23 was elevated and normalized upon TNF neutralization. Thus, the inflammatory cytokine TNF contributes to elevated systemic FGF23 levels and also triggers ectopic renal Fgf23 expression in animal models of chronic kidney disease.

Item Type:

Journal Article (Original Article)


04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension
04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry

UniBE Contributor:

Ackermann, Daniel; Leichtle, Alexander Benedikt and Fiedler, Georg Martin


600 Technology > 610 Medicine & health








Alexandra Müller

Date Deposited:

30 Dec 2019 14:20

Last Modified:

30 Dec 2019 14:20

Publisher DOI:


PubMed ID:


Uncontrolled Keywords:

bone chronic kidney disease (CKD) cytokine fibroblast growth factor 23 (FGF23) inflammation inflammatory bowel disease tumor necrosis factor (TNF)





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