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Record W1989025333 · doi:10.1359/jbmr.090516

Klotho Variants and Chronic Hemodialysis Mortality

2009· article· en· W1989025333 on OpenAlexaff
David J. Friedman, Maryam Afkarian, Hector Tamez, Ishir Bhan, Tamara Isakova, Myles Wolf, Elizabeth Ankers, Jun Ye, Marcello Tonelli, Carmine Zoccali, Makoto Kuro‐o, Orson W. Moe, S. Ananth Karumanchi, Ravi Thadhani

Bibliographic record

VenueJournal of Bone and Mineral Research · 2009
Typearticle
Languageen
FieldMedicine
TopicParathyroid Disorders and Treatments
Canadian institutionsUniversity of Alberta
FundersNational Institute of Diabetes and Digestive and Kidney DiseasesNational Heart, Lung, and Blood Institute
KeywordsKlothoHemodialysisMedicineFibroblast growth factor 23Internal medicineSingle-nucleotide polymorphismKidney diseaseProportional hazards modelGenotypeVitamin D and neurologyInternational HapMap ProjectRisk factorCohortEndocrinologyBiologyKidneyGeneGenetics

Abstract

fetched live from OpenAlex

Patients with end-stage renal disease (ESRD) suffer exceptionally high mortality rates in their first year of chronic hemodialysis. Both vitamin D and fibroblast growth factor (FGF)-23 levels correlate with survival in these patients. Klotho is a protein in the vitamin D/FGF-23 signaling pathway that has been linked with accelerated aging and early mortality in animal models. We therefore hypothesized that genetic variation in the Klotho gene might be associated with survival in subjects with ESRD. We tested the association between 12 single nucleotide polymorphisms (SNPs) in the Klotho gene and mortality in a cohort of ESRD patients during their first year on hemodialysis (n = 1307 white and Asian). We found a significant association between the CC genotype of one tag SNP, rs577912, and increased risk for 1-yr mortality (RR, 1.76; 95% CI, 1.19-2.59; p = 0.003). This effect was even more marked among patients who were not treated with activated vitamin D supplementation (HR, 2.51; 95% CI, 1.18-5.34; p = 0.005). In lymphoblastoid cell lines derived from HapMap subjects, the CC genotype was associated with a 16-21% lower Klotho expression compared with the AA/AC genotype. Our data suggest that a specific Klotho variant (rs577912) is linked to survival in ESRD patients initiating chronic hemodialysis and that therapy with activated vitamin D may modify this risk.

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.

How this classification was reachedexpand

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)0.001
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.769
Threshold uncertainty score0.203

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0010.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.076
GPT teacher head0.418
Teacher spread0.342 · 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

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations59
Published2009
Admission routes1
Has abstractyes

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