Evidence map›Paper›PMID 39695715›Full record

ArticleCritical care (London, England)2024

Urinary proteomics identifies distinct immunological profiles of sepsis associated AKI sub-phenotypes.

Ian B Stanaway, Eric D Morrell, F Linzee Mabrey, Neha A Sathe, Zoie Bailey, Sarah Speckmaier, Jordan Lo, Leila R Zelnick, Jonathan Himmelfarb, Carmen Mikacenic and 3 more

Abstract read
In one paragraph

Article in Critical care (London, England), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing 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

12 citing papers in PubMed.

  1. Review
  2. Testican-2 (SPOCK2): A multifunctional matricellular regulator.Matrix biology : journal of the International Society for Matrix Biology · 2026
    Review
  3. Review
  4. Review
  5. Article
  6. Review
  7. Dynamic HGI trajectories and their impact on survival in patients with sepsis: a machine learning prognostic model.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025
    Article
  8. The 15th Anniversary ofLife (Basel, Switzerland) · 2025
    Review
  9. Review
  10. Urinary proteomics in sepsis-associated AKI.Critical care (London, England) · 2025
    Article
  11. Article
  12. Observational
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors.

Ian B StanawayDivision of Nephrology, Department of Medicine, Kidney Research Institute, University of Washington Medical Center, 325 9th Avenue, Seattle, WA, 98104, USA.
Eric D MorrellSepsis Center of Research Excellence, SCORE-UW), University of Washington, Seattle, WA, USA.
F Linzee MabreySepsis Center of Research Excellence, SCORE-UW), University of Washington, Seattle, WA, USA.
Neha A SatheSepsis Center of Research Excellence, SCORE-UW), University of Washington, Seattle, WA, USA.
Zoie BaileySepsis Center of Research Excellence, SCORE-UW), University of Washington, Seattle, WA, USA.
Sarah SpeckmaierSepsis Center of Research Excellence, SCORE-UW), University of Washington, Seattle, WA, USA.
Jordan LoSepsis Center of Research Excellence, SCORE-UW), University of Washington, Seattle, WA, USA.
Leila R ZelnickDivision of Nephrology, Department of Medicine, Kidney Research Institute, University of Washington Medical Center, 325 9th Avenue, Seattle, WA, 98104, USA.
Jonathan HimmelfarbDivision of Nephrology, Department of Medicine, Kidney Research Institute, University of Washington Medical Center, 325 9th Avenue, Seattle, WA, 98104, USA.
Carmen MikacenicSepsis Center of Research Excellence, SCORE-UW), University of Washington, Seattle, WA, USA.
Laura EvansDivision of Pulmonary, Critical Care and Sleep Medicine, Department of Medicine, University of Washington Medical Center, Seattle, WA, USA.
Mark M WurfelDivision of Nephrology, Department of Medicine, Kidney Research Institute, University of Washington Medical Center, 325 9th Avenue, Seattle, WA, 98104, USA.
Pavan K BhatrajuDivision of Nephrology, Department of Medicine, Kidney Research Institute, University of Washington Medical Center, 325 9th Avenue, Seattle, WA, 98104, USA. Bhatraju@uw.edu.

Funding

Identification and Validation of Biological Sub-phenotypes of Sepsis-induced Acute Kidney Injury: A Precision Medicine Approach to Improve Clinical OutcomesR01DK133177 · NIDDK · UNIVERSITY OF WASHINGTON · PI Pavan Kumar Bhatraju · 2022 to 2026
$2.6M
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
Targeting CD14: A Novel Therapeutic Approach for Acute Respiratory Distress SyndromeK23HL175255 · NHLBI · UNIVERSITY OF WASHINGTON · PI Frances Linzee Mabrey · 2024 to 2026
$559k
NHLBI NIH HHS K23 HL144916NHLBI NIH HHS K23 HL175255NIDDK NIH HHS K23 DK116967NIDDK NIH HHS R01 DK133177
6 · The paper itself

Abstract

backgroundPatients with sepsis-induced AKI can be classified into two distinct sub-phenotypes (AKI-SP1, AKI-SP2) that differ in clinical outcomes and response to treatment. The biologic mechanisms underlying these sub-phenotypes remains unknown. Our objective was to understand the underlying biology that differentiates AKI sub-phenotypes and associations with kidney outcomes.

methodsWe prospectively enrolled 173 ICU patients with sepsis from a suspected respiratory infection (87 without AKI and 86 with AKI on enrollment). Among the AKI patients, 66 were classified as AKI-SP1 and 20 as AKI-SP2 using a three-plasma biomarker classifier. Aptamer-based proteomics assessed 5,212 proteins in urine collected on ICU admission. We compared urinary protein abundances between AKI sub-phenotypes, conducted pathway analyses, tested associations with risk of RRT and blood bacteremia, and predicted AKI-SP2 class membership using LASSO. MEASUREMENT AND MAIN

resultsIn total, 117 urine proteins were higher in AKI-SP2, 195 were higher in AKI-SP1 (FDR < 0.05). Urinary proteins involved in inflammation and chemoattractant of neutrophils and monocytes (CXCL1 and REG3A) and oxidative stress (SOD2) were abundant in AKI-SP2, while proteins involved in collagen deposition (GP6), podocyte derived (SPOCK2), proliferation of mesenchymal cells (IL11RA), anti-inflammatory (IL10RB and TREM2) were abundant in AKI-SP1. Pathways related to immune response, complement activation and chemokine signaling were upregulated in AKI-SP2 and pathways of cell adhesion were upregulated in AKI-SP1. Overlap was present between urinary proteins that differentiated AKI sub-phenotypes and proteins that differentiated risk of RRT during hospitalization. Variable correlation was found between top aptamers and ELISA based protein assays. A LASSO derived urinary proteomic model to classify AKI-SP2 had a mean AUC of 0.86 (95% CI: 0.69-0.99).

conclusionOur findings suggest AKI-SP1 is characterized by a reparative, regenerative phenotype and AKI-SP2 is characterized as an immune and inflammatory phenotype associated with blood bacteremia. We identified shared biology between AKI sub-phenotypes and eventual risk of RRT highlighting potential therapeutic targets. Urine proteomics may be used to non-invasively classify SP2 participants.

Indexed as

Acute Kidney InjuryBacteremiaRespiratory Tract InfectionsAdultAgedBiomarkersCritical IllnessFemaleHumansMaleMiddle AgedProspective StudiesProteomicsRenal Replacement TherapyUp-RegulationBiomarkersAcute kidney injuryIntensive care unitSepsisUrinary proteomics

Identifiers

PMID39695715
PMCPMC11654061

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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.