Interpreting the Mechanisms of CRRT in Sepsis: The Peak Concentration Hypothesis

  • C. Tetta
  • R. Bellomo
  • C. Ronco
Conference paper


Acute renal failure is increasingly seen as part of the multiple organ dysfunction syndrome (MODS) in critically ill patients [1, 2]. MODS is the most frequent cause of death in patients admitted to intensive care units (ICUs) [3]. Severe sepsis and septic shock are the primary causes of MODS [4, 5] and develop as a result of the host response to infection by Gram-negative and Gram-positive bacteria [6]. Sepsis encompasses a complex mosaic of interconnected events. Molecules such as bacterial lipopolysaccharides (LPS), microbial lipopeptides, microbial DNA, peptidoglycan and lipoteichoic acid interact with the Toll-like receptors (TLR) and related molecules (MD-2, MyD88), the principal sensors of the innate immune response [7–9]. Stimulus-receptor coupling activates different signal transduction pathways leading to exacerbated generation of cytokines, and phospholipase A2-dependent, arachidonic acid-derived platelet-activating factor (PAF), leukotrienes, and thromboxanes. At the plasma level, activation of the complement (C3a, C5a, and their desarginated products) and coagulation pathways interacts with the process as products generated in the fluid phase may in turn trigger and sustain cell activation. Other agents play a role in the pathophysiology of sepsis such as surface-expressed and soluble adhesion molecules, kinins, thrombin, myocardial depressant substance(s), endorphin, and heat shock proteins.


Septic Shock Severe Sepsis Acute Renal Failure Septic Patient Continuous Renal Replacement Therapy 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


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Authors and Affiliations

  • C. Tetta
  • R. Bellomo
  • C. Ronco

There are no affiliations available

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