Evidence map›Paper›PMID 25970330›Full record

ArticlePloS one2015

A Drosophila model identifies a critical role for zinc in mineralization for kidney stone disease.

Thomas Chi, Man Su Kim, Sven Lang, Neelanjan Bose, Arnold Kahn, Lawrence Flechner, Sarah D Blaschko, Tiffany Zee, Gulinuer Muteliefu, Nichole Bond and 9 more

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.

0numbers the graph read from it
0cells of the map it votes in
49citing papers in PubMed
9.1field-weighted citation impact, top 2% 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

49 citing papers in PubMed, 86 citations in OpenAlex.

  1. Trial
  2. Article
  3. The role of inflammation and ROS in CaOx kidney stones.European journal of medical research · 2025
    Review
  4. Article
  5. XDH-1 inactivation causes xanthine stone formation inbioRxiv : the preprint server for biology · 2025
    Article
  6. Article
  7. Frontiers in physiology · 2025
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Article
  16. Science advances · 2022
    Article
  17. Review
  18. Review
  19. Article
  20. Review
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

19 authors at 5 institutions in 2 countries.

Thomas ChiDepartment of Urology, University of California San Francisco, San Francisco, California, United States of America.
Man Su KimCollege of Pharmacy, Inje University, Gimhae, Republic of Korea; The Buck Institute for Research on Aging, Novato, California, United States of America.
Sven LangThe Buck Institute for Research on Aging, Novato, California, United States of America.
Neelanjan BoseThe Buck Institute for Research on Aging, Novato, California, United States of America.
Arnold KahnThe Buck Institute for Research on Aging, Novato, California, United States of America.
Lawrence FlechnerDepartment of Urology, University of California San Francisco, San Francisco, California, United States of America.
Sarah D BlaschkoDepartment of Urology, University of California San Francisco, San Francisco, California, United States of America.
Tiffany ZeeThe Buck Institute for Research on Aging, Novato, California, United States of America.
Gulinuer MuteliefuThe Buck Institute for Research on Aging, Novato, California, United States of America.
Nichole BondThe Buck Institute for Research on Aging, Novato, California, United States of America.
Marysia KolipinskiThe Buck Institute for Research on Aging, Novato, California, United States of America.
Sirine C FakraThe Advanced Light Source, Lawrence Berkeley National Lab, Berkeley, California, United States of America.
Neil MandelDepartment of Medicine, Division of Nephrology, Medical College of Wisconsin, Zablocki VA Medical Center, Milwaukee, Wisconsin, United States of America.
Joe MillerDepartment of Urology, University of California San Francisco, San Francisco, California, United States of America.
Arvind RamanathanThe Buck Institute for Research on Aging, Novato, California, United States of America.
David W KillileaNutrition & Metabolism Center, Children's Hospital Oakland Research Institute, Oakland, California, United States of America.
Katja BrücknerEli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California San Francisco, San Francisco, California, United States of America; Department of Cell and Tissue Biology, University of California San Francisco, San Francisco, California, United States of America; Cardiovascular Research Institute, University of California San Francisco, San Francisco, California, United States of America.
Pankaj KapahiThe Buck Institute for Research on Aging, Novato, California, United States of America.
Marshall L StollerDepartment of Urology, University of California San Francisco, San Francisco, California, United States of America.
Buck Institute for Research on Aging · USUniversity of California, San Francisco · USBroad Center · USLawrence Berkeley National Laboratory · USMilwaukee VA Medical Center · US

Funding

Training in Renal ResearchT32DK007006 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI HOLZMAN, LAWRENCE B. · 1986 to 2023
$8.5M
UCSF KURe Career Development ProgramK12DK083021 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BASKIN, LAURENCE, CARROLL, PETER R · 2008 to 2017
$5.9M
Molecular Mechanisms of Lifespan Extension by Dietary Restriction in DrosophilaR01AG038688 · NIA · BUCK INSTITUTE FOR RESEARCH ON AGING · PI KAPAHI, PANKAJ · 2011 to 2015
$2.3M
Phase 2: Impact of Lipoic Acid on Cystine Nephrolithiasis; IND129545 (01/29/2016)R01FD005716 · FDA · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHI, TOM, STOLLER, MARSHALL · 2017 to 2022
$2.1M
Role of Circadian Clocks in Aging using DrosophilaR01AG045835 · NIA · BUCK INSTITUTE FOR RESEARCH ON AGING · PI KAPAHI, PANKAJ · 2013 to 2017
$2.1M
Optimizing Kidney Stone Management Using Metallomics and MetabolomicsP20DK100863 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI STOLLER, MARSHALL · 2013 to 2016
$1.6M
Role of mRNA translation in the effects of dietary restriction on lifespanR01AG038012 · NIA · BUCK INSTITUTE FOR RESEARCH ON AGING · PI KAPAHI, PANKAJ · 2010 to 2013
$1.5M
A model of kidney stone disease using D. melanogasterR21DK091727 · NIDDK · BUCK INSTITUTE FOR RESEARCH ON AGING · PI KAPAHI, PANKAJ, STOLLER, MARSHALL · 2012 to 2013
$528k
The role of sodium and zinc in a Drosophila model of nephrolithiasisF32DK098865 · NIDDK · BUCK INSTITUTE FOR RESEARCH ON AGING · PI BOND, NICHOLE DINELL · 2014 to 2014
$53k
FDA HHS R01 FD005716NIA NIH HHS R01 AG038012NIA NIH HHS R01 AG038688NIA NIH HHS R01 AG045835NIDDK NIH HHS F32 DK098865NIDDK NIH HHS K12-DK-07-006NIDDK NIH HHS K12 DK083021NIDDK NIH HHS P20 DK100863NIDDK NIH HHS P20 DK100863-01NIDDK NIH HHS R21 DK091727
6 · The paper itself

Abstract

Ectopic calcification is a driving force for a variety of diseases, including kidney stones and atherosclerosis, but initiating factors remain largely unknown. Given its importance in seemingly divergent disease processes, identifying fundamental principal actors for ectopic calcification may have broad translational significance. Here we establish a Drosophila melanogaster model for ectopic calcification by inhibiting xanthine dehydrogenase whose deficiency leads to kidney stones in humans and dogs. Micro X-ray absorption near edge spectroscopy (μXANES) synchrotron analyses revealed high enrichment of zinc in the Drosophila equivalent of kidney stones, which was also observed in human kidney stones and Randall's plaques (early calcifications seen in human kidneys thought to be the precursor for renal stones). To further test the role of zinc in driving mineralization, we inhibited zinc transporter genes in the ZnT family and observed suppression of Drosophila stone formation. Taken together, genetic, dietary, and pharmacologic interventions to lower zinc confirm a critical role for zinc in driving the process of heterogeneous nucleation that eventually leads to stone formation. Our findings open a novel perspective on the etiology of urinary stones and related diseases, which may lead to the identification of new preventive and therapeutic approaches.

Indexed as

AllopurinolAnimalsCation Transport ProteinsChelating AgentsDietary ProteinsDisease Models, AnimalDogsDrosophila melanogasterDrosophila ProteinsEthylenediaminesGene ExpressionHumansKidneyKidney CalculiMalpighian TubulesRNA, Small InterferingAllopurinolCation Transport ProteinsChelating AgentsDietary ProteinsDrosophila ProteinsEthylenediaminesN,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamineRNA, Small InterferingXanthine DehydrogenaseZinc

Identifiers

PMID25970330
PMCPMC4430225
OpenAlexW217662664

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.