Evidence map›Paper›PMID 24867675›Full record

ReviewCurrent opinion in nephrology and hypertension2014

Coupling fibroblast growth factor 23 production and cleavage: iron deficiency, rickets, and kidney disease.

Myles Wolf, Kenneth E White

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Current opinion in nephrology and hypertension, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
113citing papers in PubMed, 1 pooled it
–field-weighted citation impact
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

113 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Trial
  6. Effect of ferric citrate on serum phosphate and fibroblast growth factor 23 among patients with nondialysis-dependent chronic kidney disease: path analyses.Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association · 2019
    Trial
  7. Trial
  8. Trial
  9. Trial
  10. Trial
  11. Trial
  12. Article
  13. Review
  14. Current Controversies on Adequate Circulating Vitamin D Levels in CKD.International journal of molecular sciences · 2025
    Review
  15. Review
  16. Review
  17. Article
  18. Observational
  19. Article
  20. Review

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

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors.

Myles WolfaDivision of Nephrology and Hypertension, Department of Medicine and Institute for Public Health and Medicine, Feinberg School of Medicine, Northwestern University, Chicago bDepartment of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Kenneth E White

Funding

FGF23 and Cardiovascular Disease in CKDR01DK081374 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI WOLF, MYLES S · 2008 to 2016
$4.2M
FGF-23 REGULATION OF PHOSPHATE HOMEOSTASISR01DK063934 · NIDDK · INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS · PI WHITE, KENNETH E · 2003 to 2015
$3.8M
Role of FGF-23 in Mineral Metabolism Across the Spectum of Chronic Kidney DiseaseR01DK076116 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI WOLF, MYLES S · 2007 to 2016
$2.9M
FGF-23 and clinical outcomes in ADPKD patientsR01DK094796 · NIDDK · UNIVERSITY OF COLORADO DENVER · PI CHONCHOL, MICHEL BENJAMIN, GITOMER, BERENICE YOLANDE · 2012 to 2016
$2.3M
Pilot Studies Targeting Mineral Metabolism in CKDU01DK099930 · NIDDK · NORTHWESTERN UNIVERSITY AT CHICAGO · PI ISAKOVA, TAMARA · 2013 to 2018
$1.8M
Control of FGF23 Bioactivity via Circulating alpha-KlothoR01DK095784 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI WHITE, KENNETH E · 2013 to 2017
$1.7M
Mentored Patient Oriented Research in Mineral MetabolismK24DK093723 · NIDDK · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI WOLF, MYLES S · 2012 to 2016
$803k
NIDDK NIH HHS DK063934NIDDK NIH HHS DK95784NIDDK NIH HHS K24 DK093723NIDDK NIH HHS K24DK093723NIDDK NIH HHS R01 DK063934NIDDK NIH HHS R01 DK076116NIDDK NIH HHS R01DK076116NIDDK NIH HHS R01 DK081374NIDDK NIH HHS R01DK081374NIDDK NIH HHS R01 DK094796NIDDK NIH HHS R01DK094796NIDDK NIH HHS R01 DK095784NIDDK NIH HHS U01 DK099930NIDDK NIH HHS U01DK099930
6 · The paper itself

Abstract

purpose of reviewHigh levels of fibroblast growth factor 23 (FGF23) cause the rare disorders of hypophosphatemic rickets and are a risk factor for cardiovascular disease and death in patients with chronic kidney disease (CKD). Despite major advances in understanding FGF23 biology, fundamental aspects of FGF23 regulation in health and in CKD remain mostly unknown. RECENT

findingsAutosomal dominant hypophosphatemic rickets (ADHR) is caused by gain-of-function mutations in FGF23 that prevent its proteolytic cleavage, but affected individuals experience a waxing and waning course of phosphate wasting. This led to the discovery that iron deficiency is an environmental trigger that stimulates FGF23 expression and hypophosphatemia in ADHR. Unlike osteocytes in ADHR, normal osteocytes couple increased FGF23 production with commensurately increased FGF23 cleavage to ensure that normal phosphate homeostasis is maintained in the event of iron deficiency. Simultaneous measurement of FGF23 by intact and C-terminal assays supported these breakthroughs by providing minimally invasive insight into FGF23 production and cleavage in bone. These findings also suggest a novel mechanism of FGF23 elevation in patients with CKD, who are often iron deficient and demonstrate increased FGF23 production and decreased FGF23 cleavage, consistent with an acquired state that mimics the molecular pathophysiology of ADHR. SUMMARY: Iron deficiency stimulates FGF23 production, but normal osteocytes couple increased FGF23 production with increased cleavage to maintain normal circulating levels of biologically active hormone. These findings uncover a second level of FGF23 regulation within osteocytes, failure of which culminates in elevated levels of biologically active FGF23 in ADHR and perhaps CKD.

Indexed as

Iron DeficienciesBone and BonesFamilial Hypophosphatemic RicketsFibroblast Growth Factor-23Fibroblast Growth FactorsGene Expression RegulationHomeostasisHumansOsteocytesPhosphatesRenal Insufficiency, ChronicRicketsFGF23 protein, humanFibroblast Growth Factor-23Fibroblast Growth FactorsPhosphates

Identifiers

PMID24867675
PMCPMC4322859

What OpenQuestion holds

Textmetadata
LicenceTDM
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.