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12:40
13:45
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Kent DoiJapan
Speaker
Organ Crosstalk in AKIAcute kidney injury (AKI) is frequently complicated by distant organ dysfunction, significantly increasing patient morbidity and mortality. Recent clinical and experimental evidence highlights complex inter-organ crosstalk mechanisms, such as systemic cytokine release, oxidative stress, immune dysregulation, and damage-associated molecular patterns (DAMPs), that mediate extrarenal tissue injury. Experimental studies demonstrate distinct pathophysiological axes connecting the injured kidney with the heart and lungs. Specifically, mitochondrial dysfunction plays a critical role in acute cardiorenal syndrome. Furthermore, in AKI-induced acute lung injury, in addition to activation of the HMGB1–Toll-like receptor 4 (TLR4) pathway and formation of neutrophil extracellular traps (NETs), recent studies have reported a novel pathophysiological mechanism of impaired gas exchange mediated by neutrophil retention. This presentation provides an updated overview of the molecular pathways driving AKI-induced distant organ crosstalk, emphasizing key pathophysiology involving the heart and lungs, and discusses targeted therapeutic strategies to improve clinical outcomes in multi-organ failure.Heterogeneity and Future Direction of Major Adverse Kidney EventsThe "AKI/AKD/CKD axis" represents a critical continuum in nephrology, highlighting that acute kidney injury (AKI) is not merely a self-limiting episode but a potent driver of chronic kidney disease (CKD). Numerous clinical studies have reported the epidemiology of the AKI-to-CKD transition, demonstrating how recurrent or severe AKI accelerates renal decline. Crucially, methodological heterogeneity in defining Major Adverse Kidney Events (MAKE), as highlighted by our recent scoping review (Maeda et al., Intensive Care Med 2024), complicates the interpretation of clinical trial outcomes. To ensure the success of future clinical trials targeting AKI and the AKI-to-CKD transition, we must not only identify optimal therapeutic targets, but also establish standardized outcomes that directly align with improved patient care.Targeted Polymyxin B Hemadsorption in Sepsis: Lessons from Japanese Experience and Patient SelectionPolymyxin B haemadsorption (PMX-HA) has a long clinical history in Japan in the treatment of endotoxemia and septic shock. However, recent international randomized controlled trials and clinical guidelines have caused controversy regarding its routine use, citing inconsistent survival benefits in unselected populations. This presentation reviews the evolution of PMX-HA, from its origins in extensive Japanese clinical experience to modern precision medicine approaches in intensive care. Recent secondary analyses and real-world studies have highlighted significant heterogeneity in treatment effects, underscoring the necessity of appropriate patient selection. Subgroup analyses from the EUPHRATES trial demonstrated the potential efficacy of PMX-HA in patients with moderate-to-high endotoxin activity levels (EAA 0.6–0.9) and high severity of organ failure. Furthermore, machine learning applications such as causal forest modelling on large observational and trial cohorts have successfully identified specific biomarker profiles and clinical characteristics that define true responders.
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Yen-Ta HuangTaiwan
Speaker
From Guidelines to Bayesian Trials: How Should We Interpret Polymyxin B Hemoadsorption in Sepsis?Polymyxin B hemoadsorption has occupied an unusually contested place in sepsis care, and the way authoritative bodies describe it has shifted over time. This talk traces that evolution—from the 2020 Taiwan AKI consensus through the 2021 and 2026 Surviving Sepsis Campaign guidelines—and uses the changing recommendations as a lens on the methodological debates that underlie them.
From an evidence-based medicine standpoint, the controversy is less about the device than about how we generate and grade evidence. I will first examine the frequentist evidence base, including our network meta-analysis of blood purification therapies for severe infection and sepsis/septic shock published in Critical Care Medicine. I will outline what a network meta-analysis adds—coherent ranking across multiple modalities, indirect comparison, and explicit quantification of heterogeneity—while being candid about its limitations, including reliance on the transitivity assumption, sparse networks, and the fragility of mortality estimates pooled from heterogeneous trials.
I will then turn to the recently reported TIGRIS trial, which used a Bayesian, enrichment-based phase 3 design with prespecified borrowing from the EUPHRATES treatable cohort. I will highlight the strengths of the Bayesian presentation—direct posterior probabilities of benefit, transparent incorporation of prior evidence, and efficiency in a rare, mechanistically defined phenotype—alongside the cautions it demands: sensitivity to prior choice, the open-label design, and the gap between a high posterior probability and a confirmed effect.
Bringing these strands together, the talk offers a multifaceted, methodology-driven reading of polymyxin B hemoadsorption in sepsis, and a transferable framework for clinicians facing the increasingly common situation in which guidelines, frequentist syntheses, and Bayesian trials appear to diverge.從治療執行到品質治理:連結式重症腎臟照護與資料驅動決策
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Room 101C
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