Evidence map›Paper›PMID 30455427›Full record

ReviewNature reviews. Nephrology2019

The Klotho proteins in health and disease.

Makoto Kuro-O

Abstract readReview
PubMed Publisher
In one paragraph

Review in Nature reviews. Nephrology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 417 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
417citing papers in PubMed, 3 pooled it
18.7field-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

417 citing papers in PubMed, 3 syntheses or guidelines pooled it, 669 citations in OpenAlex.

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  12. Klotho revisited: tubular heterogeneity reshapes mineral metabolism, aging, and CKD.Pflugers Archiv : European journal of physiology · 2026
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357 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

1 author at 1 institution in 1 country.

Makoto Kuro-ODivision of Anti-aging Medicine, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan. mkuroo@jichi.ac.jp.
Jichi Medical University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Klotho proteins, αKlotho and βKlotho, are essential components of endocrine fibroblast growth factor (FGF) receptor complexes, as they are required for the high-affinity binding of FGF19, FGF21 and FGF23 to their cognate FGF receptors (FGFRs). Collectively, these proteins form a unique endocrine system that governs multiple metabolic processes in mammals. FGF19 is a satiety hormone that is secreted from the intestine on ingestion of food and binds the βKlotho-FGFR4 complex in hepatocytes to promote metabolic responses to feeding. By contrast, under fasting conditions, the liver secretes the starvation hormone FGF21, which induces metabolic responses to fasting and stress responses through the activation of the hypothalamus-pituitary-adrenal axis and the sympathetic nervous system following binding to the βKlotho-FGFR1c complex in adipocytes and the suprachiasmatic nucleus, respectively. Finally, FGF23 is secreted by osteocytes in response to phosphate intake and binds to αKlotho-FGFR complexes, which are expressed most abundantly in renal tubules, to regulate mineral metabolism. Growing evidence suggests that the FGF-Klotho endocrine system also has a crucial role in the pathophysiology of ageing-related disorders, including diabetes, cancer, arteriosclerosis and chronic kidney disease. Therefore, targeting the FGF-Klotho endocrine axes might have therapeutic benefit in multiple systems; investigation of the crystal structures of FGF-Klotho-FGFR complexes is paving the way for the development of drugs that can regulate these axes.

Indexed as

AgingAnimalsBiomarkersBirdsCardiovascular DiseasesEndocrine System DiseasesFibroblast Growth Factor-23Fibroblast Growth FactorsGlucuronidaseHumansHypothalamo-Hypophyseal SystemKidney DiseasesKlotho ProteinsMammalsPhosphatesPituitary-Adrenal SystemBiomarkersFGF23 protein, humanFibroblast Growth Factor-23Fibroblast Growth FactorsGlucuronidaseKlotho ProteinsPhosphates

Identifiers

PMID30455427
OpenAlexW2901082414

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.