TY - JOUR
T1 - Tumor necrosis factor stimulates fibroblast growth factor 23 levels in chronic kidney disease and non-renal inflammation
AU - Egli-Spichtig, Daniela
AU - Imenez Silva, Pedro Henrique
AU - Glaudemans, Bob
AU - Gehring, Nicole
AU - Bettoni, Carla
AU - Zhang, Martin Y.H.
AU - Pastor-Arroyo, Eva M.
AU - Schönenberger, Désirée
AU - Rajski, Michal
AU - Hoogewijs, David
AU - Knauf, Felix
AU - Misselwitz, Benjamin
AU - Frey-Wagner, Isabelle
AU - Rogler, Gerhard
AU - Ackermann, Daniel
AU - Ponte, Belen
AU - Pruijm, Menno
AU - Leichtle, Alexander
AU - Fiedler, Georg Martin
AU - Bochud, Murielle
AU - Ballotta, Virginia
AU - Hofmann, Sandra
AU - Perwad, Farzana
AU - Föller, Michael
AU - Lang, Florian
AU - Wenger, Roland H.
AU - Frew, Ian
AU - Wagner, Carsten A.
N1 - Publisher Copyright:
© 2019 International Society of Nephrology
PY - 2019/10
Y1 - 2019/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85068541907&partnerID=8YFLogxK
U2 - 10.1016/j.kint.2019.04.009
DO - 10.1016/j.kint.2019.04.009
M3 - Article
C2 - 31301888
AN - SCOPUS:85068541907
SN - 0085-2538
VL - 96
SP - 890
EP - 905
JO - Kidney International
JF - Kidney International
IS - 4
ER -