Evidence map›Paper›PMID 41232539›Full record

ArticleCell metabolism2026

Therapeutic remodeling of the ceramide backbone prevents kidney injury.

Rebekah J Nicholson, Luis Cedeño-Rosario, J Alan Maschek, Trevor Lonergan, Jonathan G Van Vranken, Angela R S Kruse, Chris J Stubben, Liping Wang, Deborah Stuart, Queren A Alcantara and 18 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing 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

6 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

28 authors.

Rebekah J NicholsonDepartment of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, UT, USA; Diabetes and Metabolism Research Center, University of Utah College of Medicine, Salt Lake City, UT, USA.
Luis Cedeño-RosarioDiabetes and Metabolism Research Center, University of Utah College of Medicine, Salt Lake City, UT, USA; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
J Alan MaschekDiabetes and Metabolism Research Center, University of Utah College of Medicine, Salt Lake City, UT, USA; Metabolomics Core Facility, University of Utah, Salt Lake City, UT, USA.
Trevor LonerganMetabolomics Core Facility, University of Utah, Salt Lake City, UT, USA.
Jonathan G Van VrankenDepartment of Cell Biology, Harvard Medical School, Cambridge, MA, USA.
Angela R S KruseDepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.
Chris J StubbenCancer Bioinformatics Resource, University of Utah Huntsman Cancer Institute, Salt Lake City, UT, USA.
Liping WangDepartment of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, UT, USA; Diabetes and Metabolism Research Center, University of Utah College of Medicine, Salt Lake City, UT, USA.
Deborah StuartDivision of Nephrology and Hypertension, University of Utah Health Department of Internal Medicine, Salt Lake City, UT, USA.
Queren A AlcantaraDiabetes and Metabolism Research Center, University of Utah College of Medicine, Salt Lake City, UT, USA; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA.
Monica P ReveloDepartment of Pathology, University of Utah School of Medicine, Salt Lake City, UT, USA.
Kate RutterDiabetes and Metabolism Research Center, University of Utah College of Medicine, Salt Lake City, UT, USA.
Mayette PahuluDiabetes and Metabolism Research Center, University of Utah College of Medicine, Salt Lake City, UT, USA.
Jacob TaloaDiabetes and Metabolism Research Center, University of Utah College of Medicine, Salt Lake City, UT, USA.
Xuanchen WuDiabetes and Metabolism Research Center, University of Utah College of Medicine, Salt Lake City, UT, USA.
Juwan KimDiabetes and Metabolism Research Center, University of Utah College of Medicine, Salt Lake City, UT, USA.
Juna KimDiabetes and Metabolism Research Center, University of Utah College of Medicine, Salt Lake City, UT, USA.
Isaac HallDivision of Nephrology and Hypertension, University of Utah Health Department of Internal Medicine, Salt Lake City, UT, USA.
Amanda J ClarkDivision of Nephrology, University of Texas Southwestern Medical Center Department of Medicine, Dallas, TX, USA; Division of Nephrology, University of Texas Southwestern Medical Center Department of Pediatrics, Dallas, TX, USA.
Samir ParikhDivision of Nephrology, University of Texas Southwestern Medical Center Department of Medicine, Dallas, TX, USA; Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Jeffrey SpragginsDepartment of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN, USA.
Donna RomeroCentaurus Therapeutics, Inc., San Francisco, CA, USA.
Jeremy T BlitzerCentaurus Therapeutics, Inc., San Francisco, CA, USA.
Steven P GygiDepartment of Cell Biology, Harvard Medical School, Cambridge, MA, USA.
Jared RutterDiabetes and Metabolism Research Center, University of Utah College of Medicine, Salt Lake City, UT, USA; Department of Biochemistry, University of Utah School of Medicine, Salt Lake City, UT, USA; Howard Hughes Medical Institute, Salt Lake City, UT, USA.
William L HollandDepartment of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, UT, USA; Diabetes and Metabolism Research Center, University of Utah College of Medicine, Salt Lake City, UT, USA.
Nirupama RamkumarDiabetes and Metabolism Research Center, University of Utah College of Medicine, Salt Lake City, UT, USA; Division of Nephrology and Hypertension, University of Utah Health Department of Internal Medicine, Salt Lake City, UT, USA.
Scott A SummersDepartment of Nutrition and Integrative Physiology, University of Utah College of Health, Salt Lake City, UT, USA; Diabetes and Metabolism Research Center, University of Utah College of Medicine, Salt Lake City, UT, USA. Electronic address: scott.a.summers@health.utah.edu.

Funding

UTAH REGIONAL CANCER CENTERP30CA042014 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Jared P Rutter · 1986 to 2026
$72.6M
Central Hub for Kidney Precision MedicineU24DK114886 · NIDDK · UNIVERSITY OF WASHINGTON · PI Jonathan Himmelfarb, Matthias Kretzler · 2022 to 2026
$21.1M
KPMP Kidney Mapping and Atlas Project (KMAP)U01DK133090 · NIDDK · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jonathan Himmelfarb, Matthias Kretzler · 2022 to 2026
$10.4M
Integrated spatial interrogation of cellular and molecular signatures of human kidney diseaseU01DK114923 · NIDDK · INDIANA UNIVERSITY INDIANAPOLIS · PI Tarek Maurice Ashkar, Pierre C Dagher · 2022 to 2026
$5.4M
Single cell multiomic and spatial atlas of acute and chronic kidney injuryU01DK114933 · NIDDK · WASHINGTON UNIVERSITY · PI Sanjay Jain · 2022 to 2026
$5.0M
Interdisciplinary Training Program in MetabolismT32DK091317 · NIDDK · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI SCOTT A SUMMERS · 2011 to 2026
$4.8M
Ceramides as novel drivers of metabolic dysfunction and colorectal cancerU01CA272529 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI Mary Christine Playdon, SCOTT A SUMMERS · 2022 to 2026
$4.7M
Dihydroceramide Desaturase-1 Inhibitors for Treatment of Diabetes and Other Metabolic DiseasesR44DK116450 · NIDDK · POTRERO HILL THERAPEUTICS, INC. · PI BLITZER, JEREMY, SUMMERS, SCOTT A · 2018 to 2022
$4.7M
Spatial Multi-Omics to Profile Metabolic Pathways for Kidney DiseaseU01DK114920 · NIDDK · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Christopher R Anderton, Kumar Sharma · 2022 to 2026
$3.9M
Boston Chronic Kidney Disease Research Biopsy CenterU01DK133092 · NIDDK · BOSTON MEDICAL CENTER · PI Sylvia E Rosas, Sushrut S. Waikar · 2022 to 2026
$3.5M
Multimodal Imaging Mass Spectrometry and Spatial Omics for the Human KidneyU01DK133766 · NIDDK · VANDERBILT UNIVERSITY · PI Jeffrey M Spraggins · 2022 to 2026
$3.4M
Liver-islet and intra-islet cross talk in alpha cell hyperplasia and beta cell regenerationR01DK112826 · NIDDK · UT SOUTHWESTERN MEDICAL CENTER · PI HOLLAND, WILLIAM L · 2017 to 2025
$3.4M
NCI NIH HHS P30 CA042014NCI NIH HHS U01 CA272529NHLBI NIH HHS R01 HL170575NIA NIH HHS R01 AG085793NIDDK NIH HHS F31 DK134088NIDDK NIH HHS R01 DK058784NIDDK NIH HHS R01 DK108833NIDDK NIH HHS R01 DK112826NIDDK NIH HHS R01 DK115824NIDDK NIH HHS R01 DK122001NIDDK NIH HHS R01 DK130296NIDDK NIH HHS R01 DK131609NIDDK NIH HHS R01 DK133271NIDDK NIH HHS R43 DK116450NIDDK NIH HHS R44 DK116450NIDDK NIH HHS T32 DK091317NIDDK NIH HHS U01 DK114866NIDDK NIH HHS U01 DK114907NIDDK NIH HHS U01 DK114908NIDDK NIH HHS U01 DK114920NIDDK NIH HHS U01 DK114923NIDDK NIH HHS U01 DK114933NIDDK NIH HHS U01 DK133081NIDDK NIH HHS U01 DK133090NIDDK NIH HHS U01 DK133091NIDDK NIH HHS U01 DK133092NIDDK NIH HHS U01 DK133093NIDDK NIH HHS U01 DK133095NIDDK NIH HHS U01 DK133097NIDDK NIH HHS U01 DK133113NIDDK NIH HHS U01 DK133766NIDDK NIH HHS U01 DK133768NIDDK NIH HHS U24 DK114886NIDDK NIH HHS UH3 DK114861NIDDK NIH HHS UH3 DK114915NIDDK NIH HHS UH3 DK114926NIDDK NIH HHS UH3 DK114937NIGMS NIH HHS R35 GM131854NIH HHS S10 OD016232NIH HHS S10 OD021505
6 · The paper itself

Abstract

Perturbation of proximal tubule (PT) lipid metabolism fuels the pathological features of acute kidney injury (AKI). We found that AKI induced biosynthesis of lipotoxic ceramides within PTs in humans and mice and that urine ceramides predicted disease severity in children and adults. Mechanistic studies in primary PTs, which included a thermal proteomic profiling screen for ceramide effectors, revealed that ceramides altered assembly of the mitochondrial contact site and cristae-organizing system (MICOS) and respiratory supercomplexes, leading to acute disruption of cristae architecture, mitochondrial morphology, and respiration. These ceramide actions were dependent on the presence of the 4,5-trans double bond inserted by dihydroceramide desaturase 1 (DES1). Genetically ablating DES1 preserved mitochondrial integrity and prevented kidney injury in mice following bilateral ischemia reperfusion. Moreover, novel DES1 inhibitors that are attractive clinical drug candidates phenocopied the DES1 knockouts. These studies describe a new, therapeutically tractable mechanism underlying PT mitochondrial damage in AKI.

Indexed as

Acute Kidney InjuryCeramidesAdultAnimalsChildFemaleHumansKidney Tubules, ProximalMaleMiceMice, Inbred C57BLMice, KnockoutMitochondriaOxidoreductasesReperfusion InjuryCeramidesdihydroceramide desaturaseOxidoreductasesacute kidney injuryceramidescristaeETClipid metabolismlipidomicsmetabolismMICOSmitochondriaproximal tubulesphingolipids

Identifiers

PMID41232539
PMCPMC12700610

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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.