Evidence map›Paper›PMID 37949747›Full record

ArticleJournal of cystic fibrosis : official journal of the European Cystic Fibrosis Society2024

Identification of prognostic biomarkers for antibiotic associated nephrotoxicity in cystic fibrosis.

Andrew Hart, Francine Cesar, Leila R Zelnick, Nick O'Connor, Zoie Bailey, Jordan Lo, Kirk Van Ness, Ian B Stanaway, Theo K Bammler, James W MacDonald and 6 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
0.3field-weighted citation impact, top 52% 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

3 citing papers in PubMed, 3 citations in OpenAlex.

  1. Article
  2. Review
  3. 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

16 authors at 1 institution in 1 country.

Andrew HartUniversity of Washington School of Medicine, Seattle, USA.
Francine CesarDepartment of Pharmaceutics, University of Washington, Seattle, USA.
Leila R ZelnickKidney Research Institute and Division of Nephrology, Department of Medicine, University of Washington, Seattle, USA.
Nick O'ConnorDivision of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, USA.
Zoie BaileyDivision of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, USA.
Jordan LoDivision of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, USA.
Kirk Van NessDepartment of Pharmaceutics, University of Washington, Seattle, USA.
Ian B StanawayKidney Research Institute and Division of Nephrology, Department of Medicine, University of Washington, Seattle, USA.
Theo K BammlerDivision of Pediatric Pulmonary Medicine, University of Washington, Seattle, USA.
James W MacDonaldDepartment of Environmental and Occupational Health Sciences, University of Washington, Seattle, USA.
Matthew R ThauDivision of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, USA.
Jonathan HimmelfarbKidney Research Institute and Division of Nephrology, Department of Medicine, University of Washington, Seattle, USA.
Christopher H GossDivision of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, USA; Division of Pediatric Pulmonary Medicine, University of Washington, Seattle, USA.
Moira AitkenDivision of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, USA.
Edward J KellyDepartment of Pharmaceutics, University of Washington, Seattle, USA.
Pavan K BhatrajuKidney Research Institute and Division of Nephrology, Department of Medicine, University of Washington, Seattle, USA; Division of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, USA. Electronic address: bhatraju@uw.edu.
University of Washington · US

Funding

XENOBIOTIC BIOTRANSFORMATION AND DISPOSITIONP30ES007033 · NIEHS · UNIVERSITY OF WASHINGTON · PI Sheela Sathyanarayana · 1995 to 2026
$42.5M
Translational Research Center to Expedite Novel Therapies in Cystic FibrosisP30DK089507 · NIDDK · SEATTLE CHILDREN'S HOSPITAL · PI Christopher Hooper Goss · 2010 to 2026
$21.4M
The Assessment of Acute Kidney Injury Sub-phenotypes in the Intensive Care UnitK23DK116967 · NIDDK · UNIVERSITY OF WASHINGTON · PI BHATRAJU, PAVAN KUMAR · 2019 to 2023
$938k
NIDDK NIH HHS K23 DK116967NIDDK NIH HHS P30 DK089507NIEHS NIH HHS P30 ES007033
6 · The paper itself

Abstract

backgroundOur objective was to discover novel urinary biomarkers of antibiotic-associated nephrotoxicity using an ex-vivo human microphysiological system (MPS) and to translate these findings to a prospectively enrolled cystic fibrosis (CF) population receiving aminoglycosides and/or polymyxin E (colistin) for a pulmonary exacerbation.

methodsWe populated the MPS with primary human kidney proximal tubule epithelial cells (PTECs) from three donors and modeled nephrotoxin injury through exposure to 50 µg/mL polymyxin E for 72 h. We analyzed gene transcriptional responses by RNAseq and tested MPS effluents. We translated candidate biomarkers to a CF cohort via analysis of urine collected prior to, during and two weeks after antibiotics and patients were followed for a median of 3 years after antibiotic use.

resultsPolymyxin E treatment resulted in a statistically significant increase in the pro-apoptotic Fas gene relative to control in RNAseq of MPS: fold-change = 1.63, FDR q-value = 7.29 × 10

conclusionsUsing an ex-vivo MPS, we identified a novel biomarker of proximal tubule epithelial cell injury, sFas, and translated these findings to a clinical cohort of patients with CF.

Indexed as

Anti-Bacterial AgentsBiomarkersCystic FibrosisAcute Kidney InjuryAdultAminoglycosidesfas ReceptorFemaleHumansKidney Tubules, ProximalMalePrognosisProspective StudiesAminoglycosidesAnti-Bacterial AgentsBiomarkersFAS protein, humanfas ReceptorChronic kidney injuryNephrotoxicityUrinary biomarkers

Identifiers

PMID37949747
PMCPMC11076417
OpenAlexW4388573339

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.