Cardiorenal Syndrome Type 5 in Sepsis: Role of Endotoxin in Cell Death Pathways and Inflammation

Kidney Blood Press Res. 2016;41(6):1008-1015. doi: 10.1159/000452602. Epub 2016 Dec 23.


Background/aims: Cardiorenal Syndrome Type 5 (CRS Type 5) is characterized by concomitant cardiac and renal dysfunction in the setting of different systemic disorders, such as sepsis. In this study, we investigated the possible relationship between endotoxin levels, renal cell death and inflammation in septic patients with CRS Type 5.

Methods: We enrolled 11 patients with CRS Type 5. CRS Type 5 was defined according to the current classification system. AKI was defined by Acute Kidney Injury Network (AKIN) criteria. Acute cardiac dysfunction was documented by echocardiography as acute left and/or right ventricular dysfunction leading to decreased ejection fraction. Endotoxin activity was measured by the Endotoxin Activity Assay (EAA). Plasma from CRS Type 5 patients was incubated with renal tubular cells (RTCs) and cell death levels were evaluated. Plasma cytokines levels were measured as well.

Results: Accordingly to EAA levels, patients were divided into two groups: 45.4% of patients had low endotoxin activity level (negative EAA), while 54.5% of patients showed high endotoxin activity (positive EAA). RTCs incubated with plasma from EAA positive patients showed significantly higher apoptosis levels and higher caspase-3 activation compared to cells incubated with plasma from EAA negative patients, and a significant positive correlation was observed between EAA levels and RTC apoptosis levels. Furthermore, IL-6 and IFN-γ levels were significantly higher in CRS Type 5 patients with positive EAA.

Conclusion: Our data suggest a possible relationship between endotoxin levels and renal cell death in septic patients with CRS Type 5. Furthermore, this study highlights the presence of renal apoptosis, the immune deregulation and the strong inflammation in CRS Type 5 patients, especially in those with high endotoxin activity.

MeSH terms

  • Acute Kidney Injury / microbiology
  • Acute Kidney Injury / pathology
  • Aged
  • Cardio-Renal Syndrome / classification
  • Cardio-Renal Syndrome / microbiology*
  • Cardio-Renal Syndrome / pathology
  • Cell Death / drug effects
  • Cell Line
  • Endotoxins / blood
  • Endotoxins / pharmacology*
  • Female
  • Humans
  • Immune System Diseases
  • Inflammation / etiology*
  • Kidney Tubules / pathology
  • Male
  • Middle Aged
  • Sepsis / pathology*


  • Endotoxins