Evidence map›Paper›PMID 40892345›Full record

ArticleIntensive care medicine experimental2025

Uncovering molecular markers of the microvascular endothelial response in sepsis-associated acute kidney injury: a translational study in mice and humans.

T J van der Aart, G Molema, R M Jongman, H R Bouma, J Koeze, J Moser, M van Londen, M Hackl, A B Diendorfer, J C Ter Maaten and 2 more

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Article in Intensive care medicine experimental, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Review
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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

12 authors.

T J van der AartDepartment of Internal Medicine, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands. t.j.van.der.aart@umcg.nl.ORCID http://orcid.org/0000-0002-1518-8603
G MolemaDepartment of Pathology and Medical Biology, Medical Biology section, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
R M JongmanDepartment of Pathology and Medical Biology, Medical Biology section, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
H R BoumaDepartment of Acute Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
J KoezeDepartment of Critical Care, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
J MoserDepartment of Pathology and Medical Biology, Medical Biology section, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
M van LondenDepartment of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
M HacklTAmiRNA GmbH, Wien, Austria.
A B DiendorferTAmiRNA GmbH, Wien, Austria.
J C Ter MaatenDepartment of Internal Medicine, University Medical Center Groningen, University of Groningen, P.O. Box 30.001, 9700 RB, Groningen, The Netherlands.
M van Meurs *Department of Pathology and Medical Biology, Medical Biology section, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
M Luxen *Department of Pathology and Medical Biology, Medical Biology section, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

introductionEndothelial cells play a central role in the pathophysiology of sepsis-associated acute kidney injury (SA-AKI), yet we have limited understanding of the markers of microvascular-specific response. We therefore employed a translational approach integrating spatially resolved transcriptomics in a mouse SA-AKI model with validation in human kidney tissues and plasma, aiming to define the molecular signature of the endothelial response to SA-AKI in mice and in human patients.

methodsIn this post hoc analysis of prospectively collected data, we identified sepsis-associated target mRNAs and validated their expression via RT-qPCR in distinct renal microvascular compartments isolated by laser microdissection (LMD) from both cecal ligation and puncture (CLP) mice and post-mortem kidney biopsies of SA-AKI patients. Additionally, we measured the corresponding circulating proteins in plasma from two patient cohorts with sepsis and SA-AKI: one consisting of patients presenting to the emergency department, and the other of patients with severe sepsis requiring organ support in the ICU.

resultsWe identified several differentially expressed genes in the renal microvasculature following sepsis, including Mt1, Mt2, Saa3, Hp, C3, Sparc, Mmp8, and Chil3. Whole-organ samples from CLP mice also showed increased expression in the liver and lung. Except for SPARC, all genes were similarly upregulated in human kidney biopsies from SA-AKI patients. Circulating protein levels were elevated in sepsis and SA-AKI patients compared to controls; however, only CHI3L1 and MMP8 showed significantly higher levels in SA-AKI versus sepsis across both early and advanced stages.

conclusionOur findings reveal markers of the microvascular response to sepsis, which include increased levels of HP, C3, Chil3/CHI3L1, and MMP8, both at the transcriptomic level in mouse and human kidney microvasculature and at the protein level in circulating plasma of SA-AKI patients. The upregulation of these markers was shared across multiple organs and may reflect widespread endothelial activation contributing to sepsis pathophysiology.

Indexed as

Acute kidney injuryEarly diagnosticsEmergency departmentEndothelial activationEndothelial cellsIntensive care unitSA-AKISepsis

Identifiers

PMID40892345
PMCPMC12405097

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