Evidence map›Paper›PMID 30451736›Full record

ReviewCurrent opinion in nephrology and hypertension2019

Fibroblast growth factor 23 and α-Klotho co-dependent and independent functions.

L Darryl Quarles

Abstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Current opinion in nephrology and hypertension, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 7% 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

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 58 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. ACE2 deficiency protects against heme protein-induced acute kidney injury.American journal of physiology. Renal physiology · 2025
    Article
  6. Review
  7. Review
  8. Editorial: Endocrine insights into heart disease.Frontiers in endocrinology · 2025
    Article
  9. Emerging concepts on the FGF23 regulation and activity.Molecular and cellular biochemistry · 2025
    Review
  10. Review
  11. Review
  12. Article
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Article
  19. Review
  20. Article
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

1 author at 1 institution in 1 country.

L Darryl QuarlesDivision of Nephrology, Department of Medicine, College of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
University of Tennessee Health Science Center · US

Funding

Regulation and Function of FGF23R01AR045955 · NIAMS · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI QUARLES, L DARRYL · 1999 to 2016
$4.8M
Optimization of Novel Small Molecules to Antagonize FGF-23R01DK121132 · NIDDK · UNIVERSITY OF TENNESSEE HEALTH SCI CTR · PI XIAO, ZHOUSHENG · 2019 to 2023
$1.5M
NIAMS NIH HHS R01 AR045955NIDDK NIH HHS R01 DK121132
6 · The paper itself

Abstract

purpose of reviewThe current review examines what is known about the FGF-23/α-Klotho co-dependent and independent pathophysiological effects, and whether FGF-23 and/or α-Klotho are potential therapeutic targets. RECENT

findingsFGF-23 is a hormone derived mainly from bone, and α-Klotho is a transmembrane protein. Together they form a trimeric signaling complex with FGFRs in target tissues to mediate the physiological functions of FGF-23. Local and systemic factors control FGF-23 release from osteoblast/osteocytes in bone, and circulating FGF-23 activates FGFR/α-Klotho complexes in kidney proximal and distal renal tubules to regulate renal phosphate excretion, 1,25 (OH)2D metabolism, sodium and calcium reabsorption, and ACE2 and α-Klotho expression. The resulting bone-renal-cardiac-immune networks provide a new understanding of bone and mineral homeostasis, as well as identify other biological effects FGF-23. Direct FGF-23 activation of FGFRs in the absence of α-Klotho is proposed to mediate cardiotoxic and adverse innate immune effects of excess FGF-23, particularly in chronic kidney disease, but this FGF-23, α-Klotho-independent signaling is controversial. In addition, circulating soluble Klotho (sKl) released from the distal tubule by ectodomain shedding is proposed to have beneficial health effects independent of FGF-23. SUMMARY: Separation of FGF-23 and α-Klotho independent functions has been difficult in mammalian systems and understanding FGF-23/α-Klotho co-dependent and independent effects are incomplete. Antagonism of FGF-23 is important in treatment of hypophosphatemic disorders caused by excess FGF-23, but its role in chronic kidney disease is uncertain. Administration of recombinant sKl is an unproven therapeutic strategy that theoretically could improve the healt span and lifespan of patients with α-Klotho deficiency.

Indexed as

AnimalsBone and BonesFibroblast Growth Factor-23Fibroblast Growth FactorsGlucuronidaseHomeostasisHumansHypophosphatemiaKlotho ProteinsRenal Insufficiency, ChronicSignal TransductionFGF23 protein, humanFibroblast Growth Factor-23Fibroblast Growth FactorsGlucuronidaseKlotho Proteins

Identifiers

PMID30451736
PMCPMC6258326
OpenAlexW2901801720

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Registered trials

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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.