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Record W4392560887 · doi:10.1038/s41591-024-02854-6

Clonal hematopoiesis of indeterminate potential is associated with acute kidney injury

2024· article· en· W4392560887 on OpenAlex

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueNature Medicine · 2024
Typearticle
Languageen
FieldMedicine
TopicMyeloproliferative Neoplasms: Diagnosis and Treatment
Canadian institutionsSt. Joseph’s Healthcare HamiltonMcMaster UniversityPopulation Health Research InstituteImpactQueen's University
FundersCIHR Skin Research Training CentreNational Institute of Environmental Health SciencesNational Institute of Diabetes and Digestive and Kidney DiseasesNational Human Genome Research InstituteNational Heart, Lung, and Blood InstituteGillings School of Public HealthNational Institute on AgingGovernment of CanadaDeutsche ForschungsgemeinschaftNational Institute on Minority Health and Health DisparitiesPhysicians' Services Incorporated FoundationNational Institutes of HealthU.S. Department of Health and Human ServicesBroad InstituteCanadian Institutes of Health ResearchU.S. Department of Veterans Affairs
KeywordsAcute kidney injuryMedicineMendelian randomizationProinflammatory cytokineDialysisKidney diseasePopulationInternal medicineOncologyBiologyInflammationGeneGeneticsGenotype

Abstract

fetched live from OpenAlex

Abstract Age is a predominant risk factor for acute kidney injury (AKI), yet the biological mechanisms underlying this risk are largely unknown. Clonal hematopoiesis of indeterminate potential (CHIP) confers increased risk for several chronic diseases associated with aging. Here we sought to test whether CHIP increases the risk of AKI. In three population-based epidemiology cohorts, we found that CHIP was associated with a greater risk of incident AKI, which was more pronounced in patients with AKI requiring dialysis and in individuals with somatic mutations in genes other than DNMT3A , including mutations in TET2 and JAK2 . Mendelian randomization analyses supported a causal role for CHIP in promoting AKI. Non- DNMT3A -CHIP was also associated with a nonresolving pattern of injury in patients with AKI. To gain mechanistic insight, we evaluated the role of Tet2 -CHIP and Jak2 V617F -CHIP in two mouse models of AKI. In both models, CHIP was associated with more severe AKI, greater renal proinflammatory macrophage infiltration and greater post-AKI kidney fibrosis. In summary, this work establishes CHIP as a genetic mechanism conferring impaired kidney function recovery after AKI via an aberrant inflammatory response mediated by renal macrophages.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesInsufficient payload (model declined to judge)
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Not applicable · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.700
Threshold uncertainty score1.000

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0010.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.006
GPT teacher head0.290
Teacher spread0.285 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it