Evidence map›Paper›PMID 26878171›Full record

ArticleThe Journal of clinical investigation2016

FGF23 signaling impairs neutrophil recruitment and host defense during CKD.

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

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 174 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
174citing papers in PubMed, 1 pooled it
20.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

174 citing papers in PubMed, 1 synthesis or guideline pooled it, 271 citations in OpenAlex.

  1. Pooled it
  2. Effects of sucroferric oxyhydroxide and sevelamer carbonate on chronic kidney disease-mineral bone disorder parameters in dialysis patients.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2019
    Trial
  3. The effects of tenapanor on serum fibroblast growth factor 23 in patients receiving hemodialysis with hyperphosphatemia.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2019
    Trial
  4. Trial
  5. Article
  6. Article
  7. Review
  8. FGF family in health and disease.Molecular biomedicine · 2026
    Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Review
  14. Observational
  15. Review
  16. Neutrophils and NETs in kidney disease.Nature reviews. Nephrology · 2025
    Review
  17. Article
  18. Article
  19. Article
  20. Article

114 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Jan Rossaint
Jessica Oehmichen
Hugo Van Aken
Stefan Reuter
Hermann J Pavenstädt
Melanie Meersch
Mark Unruh
Alexander Zarbock
University Hospital Münster · DEMax Planck Institute for Molecular Biomedicine · DEUniversity of New Mexico · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chronic kidney disease (CKD) has been associated with impaired host response and increased susceptibility to infections. Leukocyte recruitment during inflammation must be tightly regulated to protect the host against pathogens. FGF23 levels are increased in blood during CKD, and levels of this hormone have been associated with a variety of adverse effects in CKD patients. Here, we have shown that CKD impairs leukocyte recruitment into inflamed tissue and host defense in mice and humans. FGF23 neutralization during CKD in murine models restored leukocyte recruitment and host defense. Intravital microscopy of animals with chronic kidney failure showed that FGF23 inhibits chemokine-activated leukocyte arrest on the endothelium, and downregulation of FGF receptor 2 (FGFR2) on PMNs rescued host defense in these mice. In vitro, FGF23 inhibited PMN adhesion, arrest under flow, and transendothelial migration. Mechanistically, FGF23 binding to FGFR2 counteracted selectin- and chemokine-triggered β2 integrin activation on PMNs by activating protein kinase A (PKA) and inhibiting activation of the small GTPase Rap1. Moreover, knockdown of PKA abolished the inhibitory effect of FGF23 on integrin activation. Together, our data reveal that FGF23 acts directly on PMNs and dampens host defense by direct interference with chemokine signaling and integrin activation.

Indexed as

Immunity, CellularNeutrophil InfiltrationAgedAnimalsCase-Control StudiesCD18 AntigensFemaleFibroblast Growth Factor-23Fibroblast Growth FactorsHEK293 CellsHL-60 CellsHumansLeukocyte RollingMaleMice, Inbred C57BLNeutrophilsCD18 AntigensFGF23 protein, humanFgf23 protein, mouseFgfr2 protein, mouseFibroblast Growth Factor-23Fibroblast Growth FactorsReceptor, Fibroblast Growth Factor, Type 2

Identifiers

PMID26878171
PMCPMC4767336
OpenAlexW2274689835

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.