Evidence map›Paper›PMID 42613631›Full record

ArticleGenome medicine2026

Modelling ischaemic AKI in human kidney organoids reveals injury-associated epithelial states and macrophage-epithelial crosstalk.

Ana B Nunez-Nescolarde, Yang Liao, Laura Perlaza-Jiménez, Mehran Piran, Zhengqi Cheng, Chris K Barlow, Joel R Steele, Deanna Deveson, Julie L M Moreau, Han-Chung Lee and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Genome medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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.

Ana B Nunez-NescolardeDepartment of Anatomy and Developmental Biology, Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia.
Yang LiaoDepartment of Biochemistry and Molecular Biology, Cancer Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia.
Laura Perlaza-JiménezDepartment of Biochemistry and Molecular Biology, Cancer Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia.
Mehran PiranDepartment of Anatomy and Developmental Biology, Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia.
Zhengqi ChengDepartment of Anatomy and Physiology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, 3010, Australia.
Chris K BarlowMonash Proteomics and Metabolomics Facility, Monash University, Clayton, Victoria, 3800, Australia.
Joel R SteeleMonash Proteomics and Metabolomics Facility, Monash University, Clayton, Victoria, 3800, Australia.
Deanna DevesonMonash Bioinformatics Platform, Monash University, Clayton, Victoria, 3800, Australia.
Julie L M MoreauDepartment of Anatomy and Developmental Biology, Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia.
Han-Chung LeeMonash Proteomics and Metabolomics Facility, Monash University, Clayton, Victoria, 3800, Australia.
Jinhua LiDepartment of Nephrology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510180, China.
Ralf B SchittenhelmMonash Proteomics and Metabolomics Facility, Monash University, Clayton, Victoria, 3800, Australia.
Christine A WellsDepartment of Anatomy and Physiology, Faculty of Medicine, Dentistry and Health Sciences, The University of Melbourne, Melbourne, Victoria, 3010, Australia.
Wei ShiDepartment of Biochemistry and Molecular Biology, Cancer Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia.
David J Nikolic-PatersonDepartment of Nephrology, Monash Health and Monash University Centre for Inflammatory Diseases, Monash Medical Centre, Clayton, Victoria, 3168, Australia.
Alexander N CombesDepartment of Anatomy and Developmental Biology, Development and Stem Cells Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria, 3800, Australia. alex.combes@monash.edu.

Funding

Australian Research Council DP230103097Medical Research Future Fund APP2016033National Health and Medical Research Council of Australia APP1156567
6 · The paper itself

Abstract

backgroundAcute kidney injury (AKI) is a common clinical syndrome associated with high morbidity and progression to chronic kidney disease. Ischaemia is a leading cause of AKI, driving cellular stress, metabolic reprogramming, and injury-associated epithelial states. Scalable human models that enable controlled investigation of ischaemic injury, repair, and therapeutic targets in AKI remain limited. We therefore assessed the extent to which induced pluripotent stem cell (iPSC)-derived human kidney organoids recapitulate key features of ischaemic AKI.

methodsKidney organoids were subjected to hypoxic injury (1% O₂, 48 h) followed by normoxic recovery. Transcriptomic, proteomic, metabolomic, single-cell, and spatial profiling were performed across acute injury and recovery phases. iPSC-derived macrophages were integrated into organoids and analysed following hypoxic injury.

resultsHypoxia induced acute stress responses, including hypoxia-inducible factor activation, glycolytic reprogramming, cell cycle arrest, and induction of injury markers. Following recovery, organoids exhibited sustained inflammatory signalling and persistent metabolic dysregulation. Single-cell analysis revealed loss of cell type-specific markers and key functional genes across nephron segments. After return to normoxia, podocyte and distal tubule markers were largely restored, whereas proximal tubule markers showed only partial recovery. Injury-associated and inflammatory programs persisted across all nephron cell types, including upregulation of GDF15, MMP7, SPP1, CXCL2, and ICAM1, with enrichment of complement, TNF-NFκB, and lipid-associated inflammatory pathways. Injured proximal tubules were enriched for adaptive/maladaptive repair signatures derived from human kidney biopsies and displayed heterogeneous recovery. While some cells restored canonical identity, others retained dedifferentiated injury-associated states, including focal expression of CDKN1A and VCAM1. Integrated macrophages transitioned from homeostatic, resident-like profiles to activated phenotypes following injury, exhibiting spatially localised interactions with injured tubules and increased expression of cytokines, chemokines, and matrix-remodelling factors.

conclusionsHuman kidney organoids recapitulate key epithelial features of hypoxic injury, including segment-specific vulnerability, persistent inflammatory signalling, and heterogeneous recovery, with integrated macrophages adopting activated inflammatory states following injury. While constrained by developmental immaturity, this system provides a tractable human platform to investigate injury-associated epithelial states and macrophage-epithelial crosstalk in AKI.

Indexed as

Acute Kidney InjuryCell CommunicationEpithelial CellsIschemiaKidneyMacrophagesModels, BiologicalOrganoidsHumansInduced Pluripotent Stem CellsAcute kidney injuryEpithelial repairHypoxiaInjury-associated cell statesIschemic acute kidney injuryKidney organoidsMacrophagesMetabolic reprogrammingSingle-cell transcriptomicsSpatial transcriptomics

Identifiers

PMID42613631
PMCPMC13487967

What Socratic holds

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Registered trials

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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 Socratic graph.