Pathways of renal injury in systemic gram-negative sepsis

Eur J Clin Invest. 2008 Oct;38 Suppl 2:39-44. doi: 10.1111/j.1365-2362.2008.02007.x.


Acute renal failure is a grave complication of systemic gram-negative sepsis. The pathophysiological mechanisms of sepsis leading to kidney injury result in part from systemic inflammatory and haemodynamic alterations. These are triggered by the interaction of endotoxin with Toll-like receptor 4 (TLR4) on cells of the immune system. Recently, TLR4 and other co-effector molecules were identified on renal tubular and vascular cells. Furthermore, it was demonstrated that systemic endotoxin has direct access to renal sites where these receptors are expressed. Therefore, we review data in support of this novel pathway of renal injury in sepsis, whereby systemic endotoxin causes direct injury through interactions with local epithelial and endothelial TLR4.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Acute Kidney Injury / immunology
  • Acute Kidney Injury / metabolism
  • Acute Kidney Injury / pathology*
  • Animals
  • Endothelial Cells / metabolism
  • Endotoxins / metabolism
  • Gram-Negative Bacterial Infections / metabolism
  • Gram-Negative Bacterial Infections / microbiology
  • Gram-Negative Bacterial Infections / pathology*
  • Humans
  • Kidney / immunology
  • Kidney / metabolism
  • Kidney / pathology*
  • Sepsis / immunology
  • Sepsis / microbiology
  • Sepsis / pathology*
  • Toll-Like Receptor 4 / metabolism


  • Endotoxins
  • TLR4 protein, human
  • Toll-Like Receptor 4