Evidence map›Paper›PMID 40232852›Full record

Observational studyJCI insight2025

A cross-sectional study of the role of epithelial cell injury in kidney transplant outcomes.

Philip F Halloran, Jessica Chang, Martina Mackova, Katelynn S Madill-Thomsen, Enver Akalin, Tarek Alhamad, Sanjiv Anand, Miha Arnol, Rajendra Baliga, Mirosław Banasik and 65 more

2 registry-linked trialsAbstract readObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in JCI insight, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–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.

NCT01299168 recruitingnot on this map

Multi-centric Observational Study to Analyse the Diagnostic Molecular Features in the Clinical Setting of Kidney Allograft Biopsies

TypeobservationalSponsorUniversity of AlbertaRan2011 to 2028Enrolled500ConditionsValidation Study of Molecular Diagnostic System, Development of Reporting System for Molecular Diagnosis, Incorporate Molecular Diagnosis Into Diagnostic Standards
NCT04239703 recruitingnot on this map

Trifecta-Kidney cfDNA-MMDx Study: Comparing the DD-cfDNA Test to MMDx Microarray Test, Central HLA Antibody Test, and Histology.

TypeobservationalSponsorUniversity of AlbertaRan2019 to 2029Enrolled300ConditionsKidney Transplant RejectionArmsMMDx, Prospera, HLA antibody
3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Observational
  2. Article
  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

75 authors.

Philip F HalloranAlberta Transplant Applied Genomics Centre and.
Jessica ChangAlberta Transplant Applied Genomics Centre and.
Martina MackovaAlberta Transplant Applied Genomics Centre and.
Katelynn S Madill-ThomsenAlberta Transplant Applied Genomics Centre and.
Enver AkalinMontefiore Medical Center, Bronx, New York, USA.
Tarek AlhamadWashington University at St. Louis, St. Louis, Missouri, USA.
Sanjiv AnandIntermountain Transplant Services, Murray, Utah, USA.
Miha ArnolUniversity of Ljubljana, Ljubljana, Slovenia.
Rajendra BaligaTampa General Hospital, Tampa, Florida, USA.
Mirosław BanasikMedical University of Wrocław, Wrocław, Poland.
Christopher D BlosserUniversity of Washington, Seattle, Washington, USA.
Georg BöhmigMedical University of Vienna, Vienna, Austria.
Daniel BrennanJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Jonathan BrombergUniversity of Maryland, Baltimore, Maryland, USA.
Klemens BuddeCharité - Universitätsmedizin Berlin, Berlin, Germany.
Andrzej ChamieniaMedical University of Gdańsk, Gdańsk, Poland.
Kevin ChowThe Royal Melbourne Hospital, Parkville, Victoria, Australia.
Michał CiszekWarsaw Medical University, Warsaw, Poland.
Declan de FreitasManchester Royal Infirmary, Manchester, United Kingdom.
Dominika Dęborska-MaterkowskaUniversity of Wisconsin, Madison, Wisconsin, USA.
Alicja Debska-ŚlizieńMedical University of Gdańsk, Gdańsk, Poland.
Arjang DjamaliUniversity of Wisconsin, Madison, Wisconsin, USA.
Leszek DomańskiPomeranian Medical University, Szczecin, Poland.
Magdalena DurlikWarsaw Medical University, Warsaw, Poland.
Gunilla EineckeHannover Medical School, Hannover, Germany.
Farsad EskandaryMedical University of Vienna, Vienna, Austria.
Richard FaticaCleveland Clinic Foundation, Cleveland, Ohio, USA.
Iman FrancisHenry Ford Transplant Institute, Detroit, Michigan, USA.
Justyna FrycMedical University of Białystok, Białystok, Poland.
John GillSt. Paul's Hospital, Vancouver, British Columbia, Canada.
Jagbir GillSt. Paul's Hospital, Vancouver, British Columbia, Canada.
Maciej GlydaWojewodzki Hospital, Poznan, Poland.
Sita GourishankarUniversity of Alberta, Edmonton, Alberta, Canada.
Marta GryczmanPomeranian Medical University, Szczecin, Poland.
Gaurav GuptaVirginia Commonwealth University, Richmond, Virginia, USA.
Petra HrubaInstitute for Experimental and Clinical Medicine, Prague, Czech Republic.
Peter HughesThe Royal Melbourne Hospital, Parkville, Victoria, Australia.
Arskarapurk JittiratUniversity Hospital Cleveland Medical Center, Cleveland, Ohio, USA.
Zeljka JurekovicUniversity Hospital Merkur, Zagreb, Croatia.
Layla KamalVirginia Commonwealth University, Richmond, Virginia, USA.
Mahmoud KamelTampa General Hospital, Tampa, Florida, USA.
Sam KantJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Nika KojcUniversity of Ljubljana, Ljubljana, Slovenia.
Joanna KonopaMedical University of Gdańsk, Gdańsk, Poland.
James LanSt. Paul's Hospital, Vancouver, British Columbia, Canada.
Roslyn B MannonUniversity of Alabama at Birmingham, Birmingham, Alabama, USA.
Arthur MatasUniversity of Minnesota, Minneapolis, Minnesota, USA.
Joanna MazurkiewiczPomeranian Medical University, Szczecin, Poland.
Marius MiglinasVilnius University Hospital Santaros Klinikos, Vilnius, Lithuania.
Thomas MuellerUniversity Hospital Zurich, Zurich, Switzerland.
Marek MyślakPomeranian Medical University, Szczecin, Poland.
Seth NarinsPinnacleHealth Transplant Associates, UPMC, Harrisburg, Pennsylvania, USA.
Beata NaumnikMedical University of Białystok, Białystok, Poland.
Anita PatelHenry Ford Transplant Institute, Detroit, Michigan, USA.
Agnieszka Perkowska-PtasińskaWarsaw Medical University, Warsaw, Poland.
Michael PictonManchester Royal Infirmary, Manchester, United Kingdom.
Grzegorz PiechaSilesian Medical University, Katowice, Poland.
Emilio PoggioCleveland Clinic Foundation, Cleveland, Ohio, USA.
Silvie Rajnochová BloudíčkovaInstitute for Experimental and Clinical Medicine, Prague, Czech Republic.
Thomas SchachtnerUniversity Hospital Zurich, Zurich, Switzerland.
Soroush ShojaiUniversity of Alberta, Edmonton, Alberta, Canada.
Majid Ln SikosanaUniversity of Alberta, Edmonton, Alberta, Canada.
Janka SlatinskáInstitute for Experimental and Clinical Medicine, Prague, Czech Republic.
Katarzyna Smykal-JankowiakWojewodzki Hospital, Poznan, Poland.
Ashish SolankiJohns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Željka Veceric HalerUniversity of Ljubljana, Ljubljana, Slovenia.
Ondrej ViklickyInstitute for Experimental and Clinical Medicine, Prague, Czech Republic.
Ksenija VucurUniversity Hospital Merkur, Zagreb, Croatia.
Matthew R WeirUniversity of Maryland, Baltimore, Maryland, USA.
Andrzej WiecekSilesian Medical University, Katowice, Poland.
Zbigniew WłodarczykUniversity Hospital No. 1, Bydgoszcz, Poland.
Harold YangPinnacleHealth Transplant Associates, UPMC, Harrisburg, Pennsylvania, USA.
Ziad ZakyCleveland Clinic Foundation, Cleveland, Ohio, USA.
Patrick T GauthierAlberta Transplant Applied Genomics Centre and.
Christian HinzeHannover Medical School, Hannover, Germany.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundExpression of acute kidney injury-associated (AKI-associated) transcripts in kidney transplants may reflect recent injury and accumulation of epithelial cells in "failed repair" states. We hypothesized that the phenomenon of failed repair could be associated with deterioration and failure in kidney transplants.

methodsWe defined injury-induced transcriptome states in 4,502 kidney transplant biopsies injury-induced gene sets and classifiers previously developed in transplants.

resultsIn principal component analysis (PCA), PC1 correlated with both acute and chronic kidney injury and related inflammation and PC2 with time posttransplant. Positive PC3 was a dimension that correlated with epithelial remodeling pathways and anticorrelated with inflammation. Both PC1 and PC3 correlated with reduced survival, with PC1 effects strongly increasing over time whereas PC3 effects were independent of time. In this model, we studied the expression of 12 "new" gene sets annotated in single-nucleus RNA-sequencing studies of epithelial cells with failed repair in native kidneys. The new gene sets reflecting epithelial-mesenchymal transition correlated with injury PC1 and PC3, lower estimated glomerular filtration rate, higher donor age, and future failure as strongly as any gene sets previously derived in transplants and were independent of nephron segment of origin and graft rejection.

conclusionThese results suggest 2 dimensions in the kidney transplant response to injury: PC1, AKI-induced changes, failed repair, and inflammation; and PC3, a response involving epithelial remodeling without inflammation. Increasing kidney age amplifies PC1 and PC3.

trial registrationINTERCOMEX (ClinicalTrials.gov NCT01299168); Trifecta-Kidney (ClinicalTrials.gov NCT04239703).

fundingGenome Canada; Natera, Inc.; and Thermo Fisher Scientific.

Indexed as

Acute Kidney InjuryEpithelial CellsGraft RejectionKidney TransplantationAdultAgedBiopsyCross-Sectional StudiesEpithelial-Mesenchymal TransitionFemaleHumansKidneyMaleMiddle AgedPrincipal Component AnalysisTranscriptomeMolecular diagnosisNephrologyOrgan transplantationTransplantation

Identifiers

PMID40232852
PMCPMC12128995

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Registered trials

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.