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Sepsis-induced acute kidney injury revisited: pathophysiology, prevention and future therapies

Zarbock, Alexandera; Gomez, Hernandob,c; Kellum, John A.b,c

Current Opinion in Critical Care: December 2014 - Volume 20 - Issue 6 - p 588–595
doi: 10.1097/MCC.0000000000000153
RENAL SYSTEM: Edited by Michael Joannidis
Editor's Choice

Purpose of review Acute kidney injury (AKI) is a common complication in critically ill patients and is associated with increased morbidity and mortality. Sepsis is the most common cause of AKI. Considerable evidence now suggests that the pathogenic mechanisms of sepsis-induced AKI are different from those seen in other causes of AKI. This review focuses on the recent advances in this area and discusses possible therapeutic interventions that might derive from these new insights into the pathogenesis of sepsis-induced AKI.

Recent findings The traditional paradigm that sepsis-induced AKI arises from ischemia has been challenged by recent evidence that total renal blood flow in is not universally impaired during sepsis, and AKI can develop in the presence of normal or even increased renal blood flow. Animal and human studies suggest that adaptive responses of tubular epithelial cells to injurious signals are responsible for renal dysfunction. Simultaneously occurring renal inflammation and microcirculatory dysfunction further amplify these mechanisms.

Summary An understanding of the pathologic mechanisms of sepsis-induced AKI emphasizes the important role of maladaptive responses to the septic insult. Preventive and therapeutic measures should be based on counteracting these maladaptive responses of tubular epithelial cells, inflammation, and microvascular dysfunction.

aDepartment of Anesthesiology, Intensive Care and Pain Medicine, University of Münster, Münster, Germany

bCenter for Critical Care Nephrology

cDepartment of Critical Care Medicine, CRISMA Center, University of Pittsburgh, Pennsylvania, USA

Correspondence to John A. Kellum, MD, MCCM, Professor of Critical Care Medicine, Medicine, Clinical and Translational Science, and Bioengineering, Director, Center for Critical Care Nephrology, 604, Scaife Hall, University of Pittsburgh, 3550 Terrace Street, Pittsburgh, PA 15261, USA. Tel: +1 412 647 8110; fax: +1 412 647 2645; e-mail:

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