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Sepsis-associated acute kidney injury: recent advances in enrichment strategies, sub-phenotyping and clinical trials

  • Matthieu Legrand,
  • Sean M. Bagshaw,
  • Pavan K. Bhatraju,
  • Azra Bihorac,
  • Ellen Caniglia,
  • Ashish K. Khanna,
  • John A. Kellum,
  • Jay Koyner,
  • Michael O. Harhay,
  • Fernando G. Zampieri,
  • Alexander Zarbock,
  • Kevin Chung,
  • Kathleen Liu,
  • Ravindra Mehta,
  • Peter Pickkers,
  • Abigail Ryan,
  • Juliane Bernholz,
  • Laura Dember,
  • Martin Gallagher,
  • Patrick Rossignol,
  • Marlies Ostermann

摘要

Acute kidney injury (AKI) often complicates sepsis and is associated with high morbidity and mortality. In recent years, several important clinical trials have improved our understanding of sepsis-associated AKI (SA-AKI) and impacted clinical care. Advances in sub-phenotyping of sepsis and AKI and clinical trial design offer unprecedented opportunities to fill gaps in knowledge and generate better evidence for improving the outcome of critically ill patients with SA-AKI. In this manuscript, we review the recent literature of clinical trials in sepsis with focus on studies that explore SA-AKI as a primary or secondary outcome. We discuss lessons learned and potential opportunities to improve the design of clinical trials and generate actionable evidence in future research. We specifically discuss the role of enrichment strategies to target populations that are most likely to derive benefit and the importance of patient-centered clinical trial endpoints and appropriate trial designs with the aim to provide guidance in designing future trials.