Evidence map›Paper›PMID 39828898›Full record

ArticleTransfusion2025

Red blood cell urate levels are linked to hemolysis in vitro and post-transfusion as a function of donor sex, population and genetic polymorphisms in SLC2A9 and ABCG2.

Alicia M Key, Eric J Earley, Vassilis L Tzounakas, Alkmini T Anastasiadi, Travis Nemkov, Daniel Stephenson, Monika Dzieciatkowska, Julie A Reisz, Gregory R Keele, Xutao Deng and 8 more

Abstract read
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In one paragraph

Article in Transfusion, 2025. 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. Trial
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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

18 authors.

Alicia M KeyDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.ORCID https://orcid.org/0000-0002-8787-8144
Eric J EarleyDepartment of Biostatistics and Epidemiology, RTI International, Research Triangle Park, North Carolina, USA.
Vassilis L TzounakasDepartment of Biochemistry, School of Medicine, University of Patras, Patras, Greece.
Alkmini T AnastasiadiDepartment of Biochemistry, School of Medicine, University of Patras, Patras, Greece.
Travis NemkovDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.ORCID https://orcid.org/0000-0001-8566-7119
Daniel StephensonDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.
Monika DzieciatkowskaDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.ORCID https://orcid.org/0000-0002-9947-2520
Julie A ReiszDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.ORCID https://orcid.org/0000-0002-7296-4963
Gregory R KeeleDepartment of Biostatistics and Epidemiology, RTI International, Research Triangle Park, North Carolina, USA.ORCID https://orcid.org/0000-0002-1843-7900
Xutao DengVitalant Research Institute, San Francisco, California, USA.
Mars StoneVitalant Research Institute, San Francisco, California, USA.
Steve KleinmanUniversity of British Columbia, Victoria, British Columbia, Canada.
Kirk C HansenDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.ORCID https://orcid.org/0000-0001-5054-838X
Philip J NorrisVitalant Research Institute, San Francisco, California, USA.ORCID https://orcid.org/0000-0003-0526-2088
Michael P BuschVitalant Research Institute, San Francisco, California, USA.
Nareg H RoubinianUniversity of San Francisco, San Francisco, California, USA.ORCID https://orcid.org/0000-0002-1063-6155
Grier P PageDepartment of Biostatistics and Epidemiology, RTI International, Research Triangle Park, North Carolina, USA.ORCID https://orcid.org/0000-0003-2582-3786
Angelo D'AlessandroDepartment of Biochemistry and Molecular Genetics, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.ORCID https://orcid.org/0000-0002-2258-6490

Funding

REDS-IV-P - CENTER FOR TRANSFUSION LABORATORY STUDIES (CTLS) - SARS-CoV-2/COVID-19 STUDIES75N92019D00033 · NHLBI · VITALANT · PI NORRIS, PHILIP J. · 2019 to 2024
$15.6M
The Impact of Oxidative Stress on Erythocyte BiologyR01HL148151 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI D'ALESSANDRO, ANGELO, KARAFIN, MATTHEW S · 2019 to 2022
$8.9M
The role of ferroptosis in red cell aging in vivo and in vitroR01HL146442 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI Angelo D'Alessandro, Adam N. Goldfarb · 2019 to 2026
$5.4M
Red blood cells from iron-deficient donors: recovery and storage qualityR01HL133049 · NHLBI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HOD, ELDAD ARIE, SPITALNIK, STEVEN L · 2016 to 2020
$3.8M
Interactions between the ADORA2b/Sphk1axis and the AE1-Hb switch in red blood cell aging in vivo and in vitroR01HL149714 · NHLBI · UNIVERSITY OF COLORADO DENVER · PI D'ALESSANDRO, ANGELO · 2020 to 2023
$2.6M
Effects of blood conservation and donor characteristics on transfused patient outcomes in a large community hospital networkR01HL126130 · NHLBI · VITALANT · PI ROUBINIAN, NAREG · 2016 to 2019
$1.9M
NHLBI NIH HHS 75N2019D00033NHLBI NIH HHS 75N92019D00033NHLBI NIH HHS HHSN2682011NHLBI NIH HHS HHSN268201100001INHLBI NIH HHS R01 HL126130NHLBI NIH HHS R01HL133049NHLBI NIH HHS R01 HL146442NHLBI NIH HHS R01HL146442NHLBI NIH HHS R01 HL148151NHLBI NIH HHS R01HL148151NHLBI NIH HHS R01 HL149714NHLBI NIH HHS R01HL149714WHI NIH HHS HHSN268201100001C
6 · The paper itself

Abstract

backgroundStorage of packed red blood cells (RBCs) for transfusion leads to biochemical and morphological changes, increasing hemolysis risk. Urate levels in blood bags at donation contribute to the molecular heterogeneity and hemolytic propensity of stored RBCs. However, studies to date have been underpowered to investigate at scale the contribution of donor demographics and genetics to the heterogeneity in urate levels across donations. STUDY DESIGN AND

methodsUrate levels were measured in 13,091 RBC units from the REDS study. Characteristics tested included hemolysis parameters (spontaneous, osmotic, oxidative) at storage end and post-transfusion hemoglobin (Hb) increments in recipients. Donor demographics, urate levels, and genetic variants were analyzed for associations with these outcomes.

resultsElevated urate levels were linked to male sex, older age, high BMI, and Asian descent. Units with high urate levels exhibited increased spontaneous and osmotic hemolysis, while oxidative hemolysis was unaffected. Genetic variants in SLC2A9 (V282I) and ABCG2 (Q141K) were strongly associated with elevated urate, particularly in Asian donors. Post-transfusion analyses revealed that units from female donors carrying these variants were associated with reduced Hb increments, with up to a 31% reduction in efficacy. This effect was not observed in male donors. DISCUSSION: RBC urate levels and genetic traits significantly impact storage quality and transfusion outcomes. These findings highlight the importance of donor molecular characteristics for optimizing transfusion strategies. Moreover, genetic and metabolic insights may inform donor recruitment efforts, providing health feedback to volunteers while ensuring effective transfusion products.

Indexed as

ATP Binding Cassette Transporter, Subfamily G, Member 2Blood DonorsErythrocytesErythrocyte TransfusionHemolysisNeoplasm ProteinsPolymorphism, GeneticUric AcidAdultFemaleGlucose Transport Proteins, FacilitativeHumansMaleMiddle AgedSex FactorsABCG2 protein, humanATP Binding Cassette Transporter, Subfamily G, Member 2Glucose Transport Proteins, FacilitativeNeoplasm ProteinsSLC2A9 protein, humanUric AcidageBMIhemoglobin incrementhemolysissextransporteruric acid

Identifiers

PMID39828898
PMCPMC11925674

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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.