ArticleCritical care (London, England)2024
Urinary proteomics identifies distinct immunological profiles of sepsis associated AKI sub-phenotypes.
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.
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Who cites it
12 citing papers in PubMed.
- Targeting integrated cell death networks in sepsis‑associated acute kidney injury: Shared regulatory nodes and diet‑related small molecule modulation (Review).International journal of molecular medicine · 2026Review
- Testican-2 (SPOCK2): A multifunctional matricellular regulator.Matrix biology : journal of the International Society for Matrix Biology · 2026Review
- Review
- Pathological triad of perioperative acute kidney injury: renal microcirculatory hypoxia, mitochondrial damage, and immuno-metabolic reprogramming.Frontiers in immunology · 2026Review
- The geriatric nutritional risk index predicts short-term mortality in older patients with urosepsis: a retrospective cohort study with external validation.Frontiers in nutrition · 2026Article
- Research Progress on Sepsis Diagnosis and Monitoring Based on Omics Technologies: A Review.Diagnostics (Basel, Switzerland) · 2025Review
- 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.] · 2025Article
- The 15th Anniversary ofLife (Basel, Switzerland) · 2025Review
- Acute kidney injury: pathogenesis and therapeutic interventions.Molecular biomedicine · 2025Review
- Urinary proteomics in sepsis-associated AKI.Critical care (London, England) · 2025Article
- The relationship between improved elderly nutritional risk index and short-term all-cause mortality in patients with urinary sepsis: a retrospective cohort study.Frontiers in nutrition · 2025Article
- Temperature trajectory in septic patients with hypothermia: When the ice begins to melt-A retrospective cohort study.Science progressObservational
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13 authors.
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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.
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