Evidence map›Paper›PMID 41043427›Full record

ArticleStem cell reports2025

APOL1 risk variants induce metabolic reprogramming of podocytes in patient-derived kidney organoids.

Heein Song, Sébastien J Dumas, Gangqi Wang, Lijun Ma, Franca Witjas, M Cristina Avramut, Cathelijne W van den Berg, Michael V Rocco, Barry I Freedman, Ton J Rabelink and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Molecular Mechanisms of APOL1-Associated Kidney Disease.International journal of molecular sciences · 2026
    Review
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

11 authors.

Heein SongDepartment of Internal Medicine (Nephrology), Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, the Netherlands.
Sébastien J DumasDepartment of Internal Medicine (Nephrology), Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, the Netherlands; The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, the Netherlands.
Gangqi WangDepartment of Internal Medicine (Nephrology), Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, the Netherlands; The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, the Netherlands.
Lijun MaDepartment of Internal Medicine, Section on Nephrology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Franca WitjasDepartment of Internal Medicine (Nephrology), Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, the Netherlands.
M Cristina AvramutDepartment of Internal Medicine (Nephrology), Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, the Netherlands.
Cathelijne W van den BergDepartment of Internal Medicine (Nephrology), Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, the Netherlands; The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, the Netherlands.
Michael V RoccoDepartment of Internal Medicine, Section on Nephrology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Barry I FreedmanDepartment of Internal Medicine, Section on Nephrology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
Ton J RabelinkDepartment of Internal Medicine (Nephrology), Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, the Netherlands; The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, the Netherlands.
H Siebe SpijkerDepartment of Internal Medicine (Nephrology), Leiden University Medical Center, Albinusdreef 2, 2333ZA Leiden, the Netherlands; The Novo Nordisk Foundation Center for Stem Cell Medicine (reNEW), Leiden University Medical Center, Leiden, the Netherlands. Electronic address: h.s.spijker@lumc.nl.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Carriers of two apolipoprotein L1 gene risk variants (RVs), termed G1 and G2, are at increased risk for chronic kidney disease. This study utilized induced pluripotent stem cells (iPSCs) derived from two patients homozygous for G1 and G2 to model human apolipoprotein L1 (APOL1)-mediated kidney disease (AMKD) in kidney organoids. Single-cell transcriptomic analysis and immunofluorescence imaging showed APOL1 upregulation in podocytes after interferon-gamma (IFN-γ) treatment. Transcriptomics and spatial dynamic metabolomics demonstrated a significant reduction in oxidative phosphorylation and tricarboxylic acid (TCA) cycle activity, along with upregulation of glycolysis and hypoxia signaling in RV podocytes. Isolated RV glomeruli exhibited no increase in maximal respiration rate following IFN-γ treatment, while iPSC-derived RV podocytes displayed a reduced number of mitochondrial branches and shorter branch length. This model presents early metabolic reprogramming of RV podocytes upon inflammatory injury and compelling evidence that mitochondrial dysfunction plays a pivotal role in the early pathophysiology of AMKD.

Indexed as

Apolipoprotein L1Cellular ReprogrammingKidneyOrganoidsPodocytesCitric Acid CycleGlycolysisHumansInduced Pluripotent Stem CellsInterferon-gammaMetabolic ReprogrammingMetabolomicsMitochondriaOxidative PhosphorylationAPOL1 protein, humanApolipoprotein L1Interferon-gammaAPOL1kidney organoidsmitochondriapodocytestem cells

Identifiers

PMID41043427
PMCPMC12790724

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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.