Evidence map›Paper›PMID 39048792›Full record

ArticleNature genetics2024

Single-cell multi-omic and spatial profiling of human kidneys implicates the fibrotic microenvironment in kidney disease progression.

Amin Abedini, Jonathan Levinsohn, Konstantin A Klötzer, Bernhard Dumoulin, Ziyuan Ma, Julia Frederick, Poonam Dhillon, Michael S Balzer, Rojesh Shrestha, Hongbo Liu and 20 more

Abstract read
In one paragraph

Article in Nature genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 142 papers.

0numbers the graph read from it
0cells of the map it votes in
142citing 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

142 citing papers in PubMed.

  1. Observational
  2. Review
  3. Article
  4. Article
  5. Article
  6. T-Cell Remodeling in Renal Fibrosis: From Acute Injury to Chronic Kidney Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  7. Article
  8. Review
  9. Renal TRPM6 but not Kv1.1 is required for magnesium homeostasis in mice.American journal of physiology. Renal physiology · 2026
    Article
  10. Review
  11. Article
  12. Review
  13. Article
  14. Review
  15. Article
  16. Article
  17. Article
  18. Review
  19. Article
  20. Article

82 more citing papers are in PubMed but not listed here.

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

30 authors.

Amin Abedini *Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
Jonathan Levinsohn *Renal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
Konstantin A KlötzerRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0009-0005-5022-2706
Bernhard DumoulinRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
Ziyuan MaRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-1512-8993
Julia FrederickRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
Poonam DhillonRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
Michael S BalzerRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0003-0508-1260
Rojesh ShresthaRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
Hongbo LiuRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
Steven VitaleRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
Andi M BergesonRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
Kishor Devalaraja-NarashimhaCardiovascular and Renal Research, Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA.
Paola GrandiGenomic Sciences, GSK-Cellzome, Heidelberg, Germany.
Tanmoy BhattacharyyaResearch and Development, GSK, Crescent Drive, Philadelphia, PA, USA.
Erding HuResearch and Development, GSK, Crescent Drive, Philadelphia, PA, USA.
Steven S PullenDepartment of Cardiometabolic Diseases Research, Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA.
Carine M Boustany-KariDepartment of Cardiometabolic Diseases Research, Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA.
Paolo GuarnieriDepartment of Cardiometabolic Diseases Research, Boehringer Ingelheim Pharmaceuticals, Ridgefield, CT, USA.
Anil KarihalooNovo Nordisk, Lexington, MA, USA.
Daniel TraumInstitute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-0195-5525
Hanying YanDepartment of Epidemiology, Biostatistics and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Kyle ColemanDepartment of Epidemiology, Biostatistics and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
Matthew PalmerDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.
Lea Sarov-BlatResearch and Development, GSK, Crescent Drive, Philadelphia, PA, USA.
Lori MortonCardiovascular and Renal Research, Regeneron Pharmaceuticals Inc., Tarrytown, NY, USA.
Christopher A HunterDepartment of Pathobiology, University of Pennsylvania School of Veterinary Medicine, Philadelphia, PA, USA.
Klaus H KaestnerInstitute for Diabetes, Obesity, and Metabolism, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-1228-021X
Mingyao LiDepartment of Epidemiology, Biostatistics and Informatics, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8180-0621
Katalin SusztakRenal, Electrolyte, and Hypertension Division, Department of Medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, USA. ksusztak@pennmedicine.upenn.edu.ORCID http://orcid.org/0000-0002-1005-3726

Funding

VIRAL VECTOR COREP30DK019525 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI DOUGLAS J EPSTEIN · 1986 to 2026
$48.3M
Human Pancreas Analysis Program for Type 1 Diabetes - HPAP-T1DU01DK112217 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI MARK A. ATKINSON, KLAUS H KAESTNER · 2021 to 2026
$46.8M
TRANSGENIC AND CHIMERIC MOUSE COREP30DK050306 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI GARY D. WU · 1997 to 2026
$32.5M
The Human Pancreas Analysis Program for Type 2 DiabetesU01DK123594 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Robert Babak Faryabi, KLAUS H KAESTNER · 2019 to 2026
$25.0M
Research Project Core 2P50DK114786 · NIDDK · CHILDREN'S HOSP OF PHILADELPHIA · PI Razzaghi Hanieh · 2017 to 2026
$9.6M
Role of the Notch Pathway in Kidney InjuryR01DK076077 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI KATALIN SUSZTAK · 2007 to 2026
$8.0M
Epigenetics of Chronic Kidney DiseaseR01DK087635 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI KATALIN SUSZTAK · 2009 to 2026
$7.0M
APOL1 associated kidney diseaseR01DK105821 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI SUSZTAK, KATALIN · 2016 to 2024
$4.6M
The role of senescent beta cells in T1D and T2DU01DK134995 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI KAESTNER, KLAUS H · 2022 to 2025
$2.8M
Training CoreTL1DK143326 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI Wei Tong · 2024 to 2026
$2.5M
Integrative analysis of spatial transcriptomics with histology images and single cellsR01HG013185 · NHGRI · UNIVERSITY OF PENNSYLVANIA · PI Mingyao Li · 2023 to 2026
$2.2M
The role of cytosolic nucleotide sensors in inflammatory fibrosisR01DK132630 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI SUSZTAK, KATALIN · 2022 to 2025
$2.0M
NIDDK NIH HHS P30 DK019525NIDDK NIH HHS P30 DK050306NIDDK NIH HHS P50 DK114786NIDDK NIH HHS R01 DK076077NIDDK NIH HHS R01 DK087635NIDDK NIH HHS R01 DK105821NIDDK NIH HHS R01 DK132630NIDDK NIH HHS TL1 DK143326U.S. Department of Health & Human Services | NIH | National Human Genome Research Institute (NHGRI) R01HG013185U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK076077U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK087635U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK105821U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) DK132630U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) P30DK019525U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) P50DK114786U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) U01DK112217U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) U01DK123594U.S. Department of Health & Human Services | NIH | National Institute of Diabetes and Digestive and Kidney Diseases (National Institute of Diabetes & Digestive & Kidney Diseases) U01DK134995
6 · The paper itself

Abstract

Kidneys are intricate three-dimensional structures in the body, yet the spatial and molecular principles of kidney health and disease remain inadequately understood. We generated high-quality datasets for 81 samples, including single-cell, single-nuclear, spot-level (Visium) and single-cell resolution (CosMx) spatial-RNA expression and single-nuclear open chromatin, capturing cells from healthy, diabetic and hypertensive diseased human kidneys. Combining these data, we identify cell types and map them to their locations within the tissue. Unbiased deconvolution of the spatial data identifies the following four distinct microenvironments: glomerular, immune, tubule and fibrotic. We describe the complex organization of microenvironments in health and disease and find that the fibrotic microenvironment is able to molecularly classify human kidneys and offers an improved prognosis compared to traditional histopathology. We provide a comprehensive spatially resolved molecular roadmap of the human kidney and the fibrotic process, demonstrating the clinical utility of spatial transcriptomics.

Indexed as

Cellular MicroenvironmentDisease ProgressionFibrosisKidneyKidney DiseasesSingle-Cell AnalysisGene Expression ProfilingHumansMultiomicsTranscriptome

Identifiers

PMID39048792
PMCPMC11592391

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.