FGF23 signaling impairs neutrophil recruitment and host defense during CKD

Rossaint, Jan; Oehmichen, Jessica; Aken, Hugo Van; Reuter, Stefan; Pavenstädt, Hermann; Meersch, Melanie; Unruh, Mark; Zarbock, Alexander

doi:10.1172/jci83470

Cited by 240 publications

(237 citation statements)

References 61 publications

Supporting

Mentioning

222

Contrasting

Unclassified

Order By: Relevance

“…Elevated FGF23 can induce left ventricular hypertrophy by activating FGF receptor 4 on cardiac myocytes [25, 26]. FGF23 signaling is involved in immune regulation through impairment of macrophage and neutrophil function [27]. Preclinical data suggest a novel role for elevated FGF23 in hematopoiesis through impairment of erythropoiesis in bone marrow cells [28].…”

Section: Discussionmentioning

confidence: 99%

Ferric Citrate Decreases Fibroblast Growth Factor 23 and Improves Erythropoietin Responsiveness in Hemodialysis Patients

et al. 2018

View full text Add to dashboard Cite

Background: Serum phosphate and vitamin D receptor activator regulate fibroblast growth factor 23 (FGF23), and iron may modulate FGF23 metabolism. The aim of the present study was to elucidate the effects of ferric citrate hydrate and lanthanum carbohydrate on serum FGF23 levels in hemodialysis patients. Methods: This prospective, open-label, multicenter study enrolled 60 patients on hemodialysis treated with lanthanum carbonate. Patients were randomly assigned to 2 groups: those switching from lanthanum carbonate to ferric citrate hydrate (ferric citrate group, n = 30) or those continuing lanthanum carbonate (control group, n = 30). Patients were monitored for 24 weeks. Endpoints included changes in FGF23, phosphate, and the dose of erythropoiesis stimulating agent (ESA), erythropoietin responsiveness index (ERI), and adverse events. Results: FGF-23 levels were significantly lower in the ferric citrate group compared with the levels in the control group (change from baseline –6,160 vs. –1,118 pg/mL; p = 0.026). There were no significant changes in serum calcium, phosphate, and intact parathyroid hormone levels in either group. The ferric citrate group had significantly increased serum iron, ferritin, and transferrin saturation. Hemoglobin levels were significantly elevated, and the dose of ESA was significantly decreased in the ferric citrate group but not in the control group. ERI and the dose of intravenous saccharated ferric oxide were significantly lower in the ferric citrate group compared with those of the control group (p = 0.015 and p = 0.002). Conclusion: In patients on hemodialysis, 24-week treatment with ferric citrate hydrate resulted in significant reduction in FGF23 and ERI independently of serum phosphate level.

show abstract

Section: Discussionmentioning

confidence: 99%

Ferric Citrate Decreases Fibroblast Growth Factor 23 and Improves Erythropoietin Responsiveness in Hemodialysis Patients

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Pretreatment of neutrophils with phosphaturic hormone FGF-23, known to increase substantially in CKD, has shown disabled production of reactive oxygen species as well as interference with integrin recruitment and chemokine signaling [40] .…”

Section: Discussionmentioning

confidence: 99%

Early Changes in Monocyte Adhesion Molecule Expression and Tumor Necrosis Factor-α Levels in Chronic Kidney Disease - A 5-Year Prospective Study

Wallquist¹,

Mansouri

Norrbäck

et al. 2016

Am J Nephrol

View full text Add to dashboard Cite

Background: Despite the absence of clinical symptoms, patients with chronic kidney disease (CKD) exhibit elevated levels of pro-inflammatory markers. To investigate whether it is possible to detect inflammatory activity and altered monocyte function at an early stage of renal disease, we studied patients with CKD stages 2-3 over 5 years. Methods: The expression of adhesion molecules on monocytes at resting state and after stimulation with formyl-methionyl-leucyl-phenylalanine (fMLP), as well as oxidative metabolism capacity was measured with flow cytometry in 108 CKD patients and healthy controls. Soluble markers of inflammation, such as cytokines, were analyzed using the Milliplex technique. Results: Patients showed significantly lower CD11b expression after stimulation during the 3rd (p = 0.002) and the 5th year (p < 0.001), together with a lower oxidative burst in response to fMLP over time (p = 0.02). The expression of CD62L on resting monocytes was lower during the 3rd (p = 0.001) and the 5th (p = 0.001) year in patients. Levels of tumor necrosis factor-α and RANTES were significantly increased (p = 0.001, p = 0.006) and interleukin-12 levels were also higher in CKD patients during the 5th year (p = 0.007). Conclusion: Monocytes in CKD stages 2-3 show emerging functional abrasions, with altered adhesion molecule expression and impaired fMLP response. These findings suggest that a transformation of monocyte function occurs at an early phase of renal impairment and may together with increased plasma levels of pro-inflammatory cytokines contribute to the higher vulnerability of CKD patients to comorbidities, such as infections and cardiovascular disease.

show abstract

“…The following were added to controls: 200 µL of medium consisting of RPMI 1640 medium (Gibco, UK), mixed with 2 mM L-glutamine (Gibco, UK), 10,000 IU/mL Penicillin (Gibco, UK) and 10,000 µg/mL Streptomycin (Gibco, UK); 200 µL of FGF-23-containing medium was added to the treatment group [22]. Then the medium tubes were incubated either on ice or at 37 ° C, while FGF23-treated tubes were incubated at 37 ° C for 10 min.…”

Section: Treatment Of Healthy Leukocytes With Fgf23 In Vitromentioning

confidence: 99%

“…This highlights the role of FGF23 as an inflammatory mediator, presumably acting through cytokine upregulation [9,[17][18][19][20][21]. Interestingly, a recent study described that FGF23 exposure inhibits neutrophil recruitment through interference of integrin expression, compromising host defense in CKD [22]. Thus, the relationship between FGF23 and innate immunity appears to be more complex than formerly assumed and would benefit from further investigations.…”

Section: Introductionmentioning

confidence: 96%

Associations of Fibroblast Growth Factor 23 with Markers of Inflammation and Leukocyte Transmigration in Chronic Kidney Disease

Wallquist

Mansouri

Norrbäck

et al. 2018

Nephron

View full text Add to dashboard Cite

Background: Patients with chronic kidney disease (CKD) show elevated levels of inflammatory markers and have an increased risk of infections as well as cardiovascular morbidity. Recent studies have implied effects of fibroblast growth factor 23 (FGF23) on inflammation in CKD. We analyzed potential correlations between levels of FGF23 with pro-inflammatory chemokines and markers of leukocyte transmigration in CKD patients. Methods: One hundred three patients with CKD 2–5ND and 54 healthy controls, had biochemical markers in blood and urine analyzed according to routine protocol. Pro-inflammatory cytokines were analyzed by Milliplex technique and leukocyte CD11b adhesion molecule expression was measured by flow cytometry. FGF23 levels were measured with ELISA technique. Treatment of leukocytes from healthy blood donors with FGF23 was performed in vitro and effects analyzed by flow cytometry. Results: Tumor necrosis factor-alpha, RANTES and interleukin (IL)-12 levels were significantly higher (p = 0.001, p < 0.001, and p < 0.001) in patients with CKD. Elevated FGF23 levels in the CKD group correlated to glomerular filtration rate, parathyroid hormone, urinary albumin excretion and phosphate as well as to IL-12 and RANTES. CD11b expression on resting granulocytes and monocytes, and on activated monocytes, was associated with FGF23. In vitro treatment of leukocytes with FGF23 reduced CD11b expression in resting as well as in formyl-methyinoyl-leucyl-phenylalanine-stimulated granulocytes (p = 0.03). Conclusion: FGF23 levels are associated with various inflammatory markers such as pro-inflammatory cytokines and adhesion molecules on innate immune cells. However, further studies are warranted to define the direct role of FGF23 in modulation of the innate immune system in CKD.

show abstract

FGF23 signaling impairs neutrophil recruitment and host defense during CKD

Cited by 240 publications

References 61 publications

Ferric Citrate Decreases Fibroblast Growth Factor 23 and Improves Erythropoietin Responsiveness in Hemodialysis Patients

Ferric Citrate Decreases Fibroblast Growth Factor 23 and Improves Erythropoietin Responsiveness in Hemodialysis Patients

Early Changes in Monocyte Adhesion Molecule Expression and Tumor Necrosis Factor-α Levels in Chronic Kidney Disease - A 5-Year Prospective Study

Associations of Fibroblast Growth Factor 23 with Markers of Inflammation and Leukocyte Transmigration in Chronic Kidney Disease

Contact Info

Product

Resources

About