Evidence map›Paper›PMID 32680471›Full record

ArticleBMC nephrology2020

Genetic variation implicates plasma angiopoietin-2 in the development of acute kidney injury sub-phenotypes.

Pavan K Bhatraju, Max Cohen, Ryan J Nagao, Eric D Morrell, Susanna Kosamo, Xin-Ya Chai, Robin Nance, Victoria Dmyterko, Joseph Delaney, Jason D Christie and 8 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC nephrology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed
2.8field-weighted citation impact, top 9% of its field
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

19 citing papers in PubMed, 31 citations in OpenAlex.

  1. Molecular Phenotyping of Sepsis and Differential Response to Fluid Resuscitation.American journal of respiratory and critical care medicine · 2025
    Trial
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
  7. Observational
  8. Review
  9. Integrated Analysis of Blood and Urine Biomarkers to Identify Acute Kidney Injury Subphenotypes and Associations With Long-term Outcomes.American journal of kidney diseases : the official journal of the National Kidney Foundation · 2023
    Article
  10. Article
  11. Review
  12. Article
  13. Artificial Intelligence in Acute Kidney Injury Prediction.Advances in chronic kidney disease · 2022
    Review
  14. Article
  15. Subphenotypes in acute kidney injury: a narrative review.Critical care (London, England) · 2022
    Review
  16. Article
  17. Review
  18. Article
  19. Identification of acute kidney injury subphenotypes.Current opinion in critical care · 2020
    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

18 authors at 4 institutions in 1 country.

Pavan K BhatrajuDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, 325 9th Avenue, Seattle, WA, 98104, USA. Bhatraju@uw.edu.ORCID 0000-0002-2606-4366
Max CohenDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, 325 9th Avenue, Seattle, WA, 98104, USA.
Ryan J NagaoDepartment of Bioengineering, University of Washington and Center for Cardiovascular Biology, Seattle, USA.
Eric D MorrellDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, 325 9th Avenue, Seattle, WA, 98104, USA.
Susanna KosamoDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, 325 9th Avenue, Seattle, WA, 98104, USA.
Xin-Ya ChaiDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, 325 9th Avenue, Seattle, WA, 98104, USA.
Robin NanceDepartment of Epidemiology, University of Washington, Seattle, USA.
Victoria DmyterkoDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, 325 9th Avenue, Seattle, WA, 98104, USA.
Joseph DelaneyDepartment of Epidemiology, University of Washington, Seattle, USA.
Jason D ChristieDivision of Pulmonary, Allergy, and Critical Care and Center for Clinical Epidemiology and Biostatistics, Department of Medicine, University of Pennsylvania, Philadelphia, USA.
Kathleen D LiuDivisions of Nephrology and Critical Care Medicine, University of California San Francisco, San Francisco, USA.
Carmen MikacenicDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, 325 9th Avenue, Seattle, WA, 98104, USA.
Sina A GharibDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, 325 9th Avenue, Seattle, WA, 98104, USA.
W Conrad LilesDepartment of Medicine, University of Washington, Seattle, USA.
Ying ZhengDepartment of Bioengineering, University of Washington and Center for Cardiovascular Biology, Seattle, USA.
David C ChristianiDepartments of Environmental Health and Epidemiology, Harvard TH Chan School of Public Health, Harvard University and Pulmonary and Critical Care Division, Cambridge, USA.
Jonathan HimmelfarbKidney Research Institute, Division of Nephrology, Department of Medicine, University of Washington, Seattle, USA.
Mark M WurfelDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington, 325 9th Avenue, Seattle, WA, 98104, USA.
University of Washington · USHarvard University · USUniversity of California, San Francisco · USUniversity of Pennsylvania · US

Funding

MOLECULAR EPIDEMIOLOGY OF ARDSR01HL060710 · NHLBI · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI CHRISTIANI, DAVID C · 2000 to 2015
$8.4M
Genetic Determinants of Outcomes in Acute Kidney InjuryU01DK084012 · NIDDK · UNIVERSITY OF WASHINGTON · PI HIMMELFARB, JONATHAN, WURFEL, MARK M · 2010 to 2019
$6.2M
Using iPSCs to model patient outcomes in nephrotic syndromeUH3TR000504 · NCATS · UNIVERSITY OF WASHINGTON · PI HIMMELFARB, JONATHAN · 2014 to 2016
$6.1M
A Tissue Engineered Human Kidney Microphysiological SystemUH2TR000504 · NCATS · UNIVERSITY OF WASHINGTON · PI HIMMELFARB, JONATHAN · 2012 to 2013
$2.1M
The Role of Alveolar Mononuclear Phagocytes in Acute Respiratory Distress SyndromeK23HL144916 · NHLBI · UNIVERSITY OF WASHINGTON · PI MORRELL, ERIC DOUGLAS · 2019 to 2023
$951k
The Assessment of Acute Kidney Injury Sub-phenotypes in the Intensive Care UnitK23DK116967 · NIDDK · UNIVERSITY OF WASHINGTON · PI BHATRAJU, PAVAN KUMAR · 2019 to 2023
$938k
NCATS NIH HHS UH2 TR000504NCATS NIH HHS UH3 TR000504NHLBI NIH HHS K23 HL144916NHLBI NIH HHS R01 HL060710NHLBI NIH HHS R01HL060710NIDDK NIH HHS K23 DK116967NIDDK NIH HHS U01 DK084012
6 · The paper itself

Abstract

backgroundWe previously identified two acute kidney injury (AKI) sub-phenotypes (AKI-SP1 and AKI-SP2) with different risk of poor clinical outcomes and response to vasopressor therapy. Plasma biomarkers of endothelial dysfunction (tumor necrosis factor receptor-1, angiopoietin-1 and 2) differentiated the AKI sub-phenotypes. However, it is unknown whether these biomarkers are simply markers or causal mediators in the development of AKI sub-phenotypes.

methodsWe tested for associations between single-nucleotide polymorphisms within the Angiopoietin-1, Angiopoietin-2, and Tumor Necrosis Factor Receptor 1A genes and AKI- SP2 in 421 critically ill subjects of European ancestry. Top performing single-nucleotide polymorphisms (FDR < 0.05) were tested for cis-biomarker expression and whether genetic risk for AKI-SP2 is mediated through circulating biomarkers. We also completed in vitro studies using human kidney microvascular endothelial cells. Finally, we calculated the renal clearance of plasma biomarkers using 20 different timed urine collections.

resultsA genetic variant, rs2920656C > T, near ANGPT2 was associated with reduced risk of AKI-SP2 (odds ratio, 0.45; 95% CI, 0.31-0.66; adjusted FDR = 0.003) and decreased plasma angiopoietin-2 (p = 0.002). Causal inference analysis showed that for each minor allele (T) the risk of developing AKI-SP2 decreases by 16%. Plasma angiopoietin-2 mediated 41.5% of the rs2920656 related risk for AKI-SP2. Human kidney microvascular endothelial cells carrying the T allele of rs2920656 produced numerically lower levels of angiopoietin-2 although this was not statistically significant (p = 0.07). Finally, analyses demonstrated that angiopoietin-2 is minimally renally cleared in critically ill subjects.

conclusionGenetic mediation analysis provides supportive evidence that angiopoietin-2 plays a causal role in risk for AKI-SP2.

Indexed as

Acute Kidney InjuryAdultAgedAngiopoietin-1Angiopoietin-2Critical IllnessEndothelial CellsFemaleGenetic Predisposition to DiseaseHumansIn Vitro TechniquesMaleMicrovesselsMiddle AgedPolymorphism, Single NucleotideReceptors, Tumor Necrosis Factor, Type IAngiopoietin-1Angiopoietin-2ANGPT1 protein, humanANGPT2 protein, humanReceptors, Tumor Necrosis Factor, Type ITNFRSF1A protein, humanAcute kidney injuryEndotheliumGenetics

Identifiers

PMID32680471
PMCPMC7368773
OpenAlexW3043207088

What Socratic holds

Textmetadata
LicenceCC BY
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Registered trials

None linked

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 Socratic graph.