Evidence map›Paper›PMID 41280053›Full record

ArticlebioRxiv : the preprint server for biology2025

Spatial Transcriptomics Identify T Cell-Driven Mechanisms of Kidney Damage in Immune Checkpoint Inhibitor-Associated Acute Interstitial Nephritis.

Qian Qin, Lennard Ostendorf, Sophia L Wells, Ce Gao, Miles Tran, Firasat M Alikhan, Xiwen Zhang, Api Chewcharat, Robert S Rider, Sean A Prell and 17 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2025. 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

27 authors.

Qian QinDivision of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0002-2119-6263
Lennard OstendorfDivision of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0003-3553-6406
Sophia L WellsDivision of Renal Medicine, Department of Internal Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Ce GaoDivision of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA, USA.
Miles TranDivision of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0009-0005-9330-9297
Firasat M AlikhanDivision of Renal Medicine, Department of Internal Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Xiwen ZhangDivision of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA, USA.
Api ChewcharatDivision of Renal Medicine, Department of Internal Medicine, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0002-1707-9988
Robert S RiderDivision of Renal Medicine, Department of Internal Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Sean A PrellDivision of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0009-0001-1228-4181
Raad B ChowdhuryHarvard Medical School, Boston, MA, USA.ORCID 0000-0002-9347-6299
Astrid WeinsHarvard Medical School, Boston, MA, USA.ORCID 0000-0002-1633-0245
Sujal I ShahDepartment of Pathology, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0002-0125-1448
Kavita MistryHarvard Medical School, Boston, MA, USA.ORCID 0000-0002-2592-7334
Teresa BowmanDana-Farber/Harvard Cancer Center, Boston, MA, USA.
Alexandra-Chloe VillaniDepartment of Medicine, Center for Immunology and Inflammatory Diseases, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0001-7461-0408
Nicole R LeBoeufHarvard Medical School, Boston, MA, USA.ORCID 0000-0002-8264-834X
Umut SelametDepartment of Medicine, Dana-Farber/Harvard Cancer Center, Boston, MA, USA.
Katherine Scovner RaviDivision of Renal Medicine, Department of Internal Medicine, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0001-8894-0790
Elad SharonDepartment of Medicine, Dana-Farber/Harvard Cancer Center, Boston, MA, USA.ORCID 0000-0002-0044-9719
David E LeafHarvard Medical School, Boston, MA, USA.ORCID 0000-0001-7875-090X
Dennis G MoledinaSection of Nephrology, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT, USA.ORCID 0000-0002-9537-9038
Meghan E SiseDivision of Nephrology, Department of Internal Medicine, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0002-4327-9713
Iwijn De VlaminckMeinig School of Biomedical Engineering, Cornell University, Ithaca, NY, USA.ORCID 0000-0001-6085-7311
Deepak A RaoDivision of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0001-9672-7746
Kevin WeiDivision of Rheumatology, Inflammation, and Immunity, Brigham and Women's Hospital, Boston, MA, USA.ORCID 0000-0002-1821-167X
Shruti GuptaHarvard Medical School, Boston, MA, USA.ORCID 0000-0002-5747-2151

Funding

VectorP30CA006516 · NCI · DANA-FARBER CANCER INSTITUTE · PI Irene M. Ghobrial · 1985 to 2026
$330.6M
Association of Dialysate Bicarbonate with Hemodynamic Instability and ArrhythmiaK23DK127248 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI Katherine Scovner Ravi · 2022 to 2026
$1.1M
A Notch-mediated fibrogenic program drives treatment failure in rheumatoid arthritisR01AR085028 · NIAMS · BRIGHAM AND WOMEN'S HOSPITAL · PI Kevin S Wei · 2025 to 2026
$1.0M
Novel Pathways and Therapeutic Targets for Cisplatin-Associated Acute Kidney InjuryK23DK125672 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI Shruti Gupta · 2022 to 2026
$998k
Early Detection and Treatment of Hematopoietic Stem Cell Transplant-Associated Thrombotic Microangiopathy (HSCT-TMA)R03DK141708 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI Shruti Gupta · 2025 to 2026
$285k
Incident Hemodialysis Electrolyte Analysis and Rhythm Trends (IHEART)R03DK144241 · NIDDK · BRIGHAM AND WOMEN'S HOSPITAL · PI RAVI, KATHERINE SCOVNER · 2025 to 2025
$269k
NCI NIH HHS P30 CA006516NIAMS NIH HHS R01 AR085028NIDDK NIH HHS K23 DK125672NIDDK NIH HHS K23 DK127248NIDDK NIH HHS R03 DK141708NIDDK NIH HHS R03 DK144241
6 · The paper itself

Abstract

Introduction: Immune checkpoint inhibitor-associated acute interstitial nephritis (ICI-AIN) is the most common finding on histopathology among patients with ICI-associated acute kidney injury (ICI-AKI). Patients with ICI-AIN often have T cell-dominant infiltration of the kidney and high tissue levels of CXCR3 ligands like CXCL9, 10, and 11; however, the mechanisms of inflammation in ICI-AIN are not well-understood. Methods: We applied a sub-cellular spatial transcriptomics platform (Xenium Prime 5K) to compare the cellular composition of kidney biopsy tissue from patients with ICI-AIN with ICI-treated patients with acute tubular necrosis (ICI-ATN). Results: Across 8 kidney biopsy specimens (4 with ICI-AIN, 4 with ICI-ATN), we analyzed 332,000 cells, comprising kidney parenchymal cells and infiltrating immune cells. Using a spatially-aware cellular neighborhood-based classification, we identified cellular niches corresponding to each part of the nephron, in addition to unique fibrotic and inflammatory niches. Gene pathway analysis identified interferon-gamma (IFN-γ)/STAT1 signaling as strongly increased in ICI-AIN compared to ICI-ATN. While all inflammatory niches were overrepresented in ICI-AIN, CD8 Conclusions: Spatial transcriptomics reveal novel insights into key differences in the pathophysiology of ICI-AIN versus ICI-ATN. IFN-γ-producing CD8

Indexed as

acute interstitial nephritisICI-AKIImmune Checkpoint Inhibitorinterferon gammaJAK-STAT1spatial transcriptomics

Identifiers

PMID41280053
PMCPMC12637725

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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 OpenQuestion graph.