Evidence map›Paper›PMID 25324355›Full record

ArticleNephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association2015

The demonstration of αKlotho deficiency in human chronic kidney disease with a novel synthetic antibody.

Sarah L Barker, Johanne Pastor, Danielle Carranza, Henry Quiñones, Carolyn Griffith, Regina Goetz, Moosa Mohammadi, Jianfeng Ye, Jianning Zhang, Ming Chang Hu and 3 more

Abstract readComparative Study
In one paragraph

Article in Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
94citing 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

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

  1. Pooled it
  2. Trial
  3. Trial
  4. Trial
  5. Article
  6. Article
  7. Serum α-Klotho and SIRT1 - Relationship with graft function, inflammation and hospitalization rates in kidney transplant recipients.Transplant international : official journal of the European Society for Organ Transplantation · 2026
    Observational
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Klotho and Clinical Outcomes in CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2024
    Observational
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

34 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

13 authors.

Sarah L BarkerBanting and Best Department of Medical Research and Department of Molecular Genetics, The Donnelly Centre, University of Toronto, Toronto, ON, Canada.
Johanne PastorDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Danielle CarranzaBanting and Best Department of Medical Research and Department of Molecular Genetics, The Donnelly Centre, University of Toronto, Toronto, ON, Canada.
Henry QuiñonesDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Carolyn GriffithCharles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Regina GoetzDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, USA.
Moosa MohammadiDepartment of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, NY, USA.
Jianfeng YeCharles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Jianning ZhangDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Ming Chang HuDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Makoto Kuro-oDepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Orson W MoeDepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA Charles and Jane Pak Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX, USA Department of Physiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Sachdev S SidhuBanting and Best Department of Medical Research and Department of Molecular Genetics, The Donnelly Centre, University of Toronto, Toronto, ON, Canada.

Funding

UT Southwestern O'Brien Kidney Research Core CenterP30DK079328 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI MOE, ORSON W · 2007 to 2021
$16.9M
MECHANISMS OF FGF RECEPTOR REGULATION AND SIGNALINGR01DE013686 · NIDCR · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI MOHAMMADI, MOOSA · 2000 to 2020
$12.3M
Klotho: Therapeutic Agent for Ischemia Reperfusion Induced Acute Kidney InjuryR01DK092461 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI HU, MING-CHANG · 2011 to 2021
$3.7M
Klotho and Phosphate in Chronic Kidney Disease: Pathogenesis and TherapeuticsR01DK091392 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI HU, MING-CHANG, MOE, ORSON W · 2011 to 2021
$3.2M
CIHR MOP-93725NIDCR NIH HHS R01 DE013686NIDCR NIH HHS R01DE13686NIDDK NIH HHS P30 DK-079328NIDDK NIH HHS P30 DK079328NIDDK NIH HHS R01 DK091392NIDDK NIH HHS R01DK091392NIDDK NIH HHS R01 DK092461NIDDK NIH HHS R01-DK092461
6 · The paper itself

Abstract

backgroundαKlotho is the prototypic member of the Klotho family and is most highly expressed in the kidney. αKlotho has pleiotropic biologic effects, and in the kidney, its actions include regulation of ion transport, cytoprotection, anti-oxidation and anti-fibrosis. In rodent models of chronic kidney disease (CKD), αKlotho deficiency has been shown to be an early biomarker as well as a pathogenic factor. The database for αKlotho in human CKD remains controversial even after years of study.

methodsWe used a synthetic antibody library to identify a high-affinity human antigen-binding fragment that recognizes human, rat and mouse αKlotho primarily in its native, rather than denatured, form.

resultsUsing an immunoprecipitation-immunoblot (IP-IB) assay, we measured both serum and urinary levels of full-length soluble αKlotho in humans and established that human CKD is associated with αKlotho deficiency in serum and urine. αKlotho levels were detectably lower in early CKD preceding disturbances in other parameters of mineral metabolism and progressively declined with CKD stages. We also found that exogenously added αKlotho is inherently unstable in the CKD milieu suggesting that decreased production may not be the sole reason for αKlotho deficiency.

conclusionSynthetic antibody libraries harbor tremendous potential for a variety of biomedical and clinical applications. Using such a reagent, we furnish data in support of αKlotho deficiency in human CKD, and we set the foundation for the development of diagnostic and therapeutic applications of anti-αKlotho antibodies.

Indexed as

AnimalsAntibodiesBiomarkersCase-Control StudiesEnzyme-Linked Immunosorbent AssayFibroblast Growth FactorsGlucuronidaseHealthy VolunteersHumansImmunoblottingImmunoglobulin Fab FragmentsImmunoprecipitationKlotho ProteinsMicePeptide LibraryRatsAntibodiesBiomarkersFibroblast Growth FactorsGlucuronidaseImmunoglobulin Fab FragmentsKlotho ProteinsPeptide Libraryassaychronic kidney diseaseklothosynthetic antibodies

Identifiers

PMID25324355
PMCPMC4309192

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.