Skip to main content

Searching for mechanisms that matter in septic acute kidney injury: an experimental study


Both hemodynamic and nonhemodynamic factors are implicated in the pathogenesis of sepsis-induced acute kidney injury (SAKI). However, despite similar septic insult, not all patients develop SAKI. The reasons for the difference in sensitivity to AKI are unknown. Therefore, we sought to analyze dynamic changes in renal hemodynamic and non-hemodynamic responses to sepsis in animals who developed AKI and those who do not.


Thirty-six pigs were anesthetized, mechanically ventilated and instrumented. After a recovery period, progressive sepsis was induced either by peritonitis (n = 13) or by i.v. infusion of Pseudomonas aeruginosa (n = 15). Eight sham-operated animals served as time-matched controls. All animals received standard ICU care including goal-directed hemodynamic management. Before and at 12, 18 and 24 hours of sepsis systemic and renal hemodynamic, microcirculatory and inflammatory variables were measured. AKI development was defined using AKIN criteria.


Fourteen pigs (50%) developed AKI (62% in peritonitis model, 40% in bacteria infusion model) with a significant increase in serum creatinine observed already at 18 hours of sepsis. There were no differences in the systemic hemodynamics and vasopressor support between AKI and non-AKI groups. Although time-dependent reduction in cortical microvascular perfusion was comparable in both groups, only AKI animals developed a progressive increase in renal vascular resistance. This intrarenal vasoconstriction was preceded by a marked overproduction of serum cytokines (TNFα, IL-6) and markers of oxidative stress (TBARS), observed already at 12 hours of sepsis. This induction of proinflammatory response was delayed in non-AKI animals.


The observed variability in susceptibility to SAKI in our models replicates that of human disease. This heterogeneity allowed us to isolate and study factors discriminating AKI from non-AKI. Early systemic inflammation coupled with late intrarenal vasoconstriction appears to be major determinant of the initiation of SAKI. Genetic and proteomic analyses underlying the observed differences are being analyzed.


The study was supported by the Research Project MSM 0021620819.

Author information

Authors and Affiliations


Rights and permissions

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

About this article

Cite this article

Benes, J., Chvojka, J., Sykora, R. et al. Searching for mechanisms that matter in septic acute kidney injury: an experimental study. Crit Care 15 (Suppl 1), P97 (2011).

Download citation

  • Published:

  • DOI:


  • Peritonitis
  • Renal Vascular Resistance
  • Microvascular Perfusion
  • Hemodynamic Management
  • Peritonitis Model