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Review
. 2014 Dec;20(6):588-95.
doi: 10.1097/MCC.0000000000000153.

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

Alexander Zarbock  1 , Hernando Gomez, John A Kellum
Affiliations
Review

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

Alexander Zarbock et al. Curr Opin Crit Care. 2014 Dec.

Abstract

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.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1. During sepsis, DAMPs, PAMPs, and cytokines may potentially injure tubular cells from the tubular and interstitial side
Inflammatory mediators derived from bacteria or immune cells are filtered in the glomerulus, enter the tubular space and can subsquently injure by tubular cells by binding to their respective receptors. In addition, cytokines, DAMPs, and PAMPs are released from extravasated leukocytes and can also activate tubular cells from the interstitial side. The activation of cytokine or DAMP/PAMP receptors may induce apoptosis or cell cycle arrest.
See this image and copyright information in PMC

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