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Volume 2 Supplement 1

ESICM LIVES 2014

  • Poster presentation
  • Open Access

0371. Temporal changes in systemic and renal inflammation and histology in a 72-hour rat model of faecal peritonitis

  • N Arulkumaran1, 2, 3,
  • M Sixma1,
  • E Ceravola4,
  • R Unwin2,
  • FW Tam3 and
  • M Singer1
Intensive Care Medicine Experimental20142(Suppl 1):P23

https://doi.org/10.1186/2197-425X-2-S1-P23

Published: 26 September 2014

Keywords

Acute Kidney InjuryCore TemperatureRenal Tubular CellTubular InjurySeptic Animal

Introduction

Mechanisms underlying sepsis-induced acute kidney injury remain uncertain with inflammation and altered haemodynamics being implicated.

Objectives

To determine temporal changes in systemic and renal inflammation, and histology, in a 72 hour fluid-resuscitated model of sepsis.

Methods

Tunnelled central venous (for fluid administration) and arterial (for BP monitoring/blood sampling) lines were inserted into male Wistar rats under isoflurane anaesthesia. Sepsis was induced 24h later by i.p. injection of faecal slurry. Fluid resuscitation was commenced at 2h post-slurry. Cardiac output was assessed by echocardiography. Animals (n=6-8 per group) were sacrificed at 6, 12, 24, 48, or 72h with kidneys taken for histological section and cytokine (IL-1β, IL-10 by ELISA) analysis, and blood samples for renal biochemistry, and pro- (IL-1β, IL-6), and anti-inflammatory cytokine (IL-10) analysis by ELISA. Renal histology was assessed by light microscopy for features of tubular injury (dilated tubules, tubular casts, cell necrosis), and cell death using TUNEL stain. Comparison was made against sham-operated controls and naïve animals. Statistics were performed using ANOVA and post-hoc Tukey's test. Values are expressed as means±standard deviation.

Results

Sham animals had values similar to naive animals. In septic animals, serum IL-6 and IL-1β were maximal at 6h; this corresponded with the highest core temperature and tachycardia, and the largest drop in stroke volume. By 24h, serum IL-6 and IL-1β fell, whereas IL-10 levels peaked; this corresponded to recovery of cardiac function and normalization of core temperature. Renal inflammation (peak renal IL-1β and lowest IL-10) was maximal at 24h when serum creatinine also peaked. By 72h, serum creatinine and IL-1β approached baseline values while renal IL-10 reached its zenith. (Table 1) Acute tubular injury was mild and sporadic, with minimal renal tubular cell death.
Table 1

Cytokine values

Group

Creatinine (µmol/l)

Serum IL-1β (pg/mL)

Renal IL-1β (pg/µg protein)

Serum IL-10(pg/mL)

Renal IL-10 (pg/µg protein)

Serum IL-6(pg/mL)

Naïve

23±2.6

1.0±0.0

135±36

24±30

207±80

0.8±0.4

6hr Sepsis

26±6

1428±1006

267±46

3390±1759

220±56

36347±27646

12hr Sepsis

21±2.5

1289±296

260±57

2939±1236

89±58

15217±13285

24hr Sepsis

30±5

1434±1601

398±87

4716±2682

180±44

8835±16422

48hr Sepsis

31±4

1008±887

318±140

3699±3745

238±121

144±172

72hr Sepsis

27±5

256±294

157±66

1410±1670

168±37

163±333

Conclusions

Temporal changes in renal inflammation and dysfunction lag behind changes in systemic inflammation and cardiac dysfunction. Renal dysfunction, as measured by serum creatinine, corresponds to renal inflammation. Cell death does is not a predominant feature, and does not account for the renal dysfunction seen in this sepsis model.

Declarations

Grant acknowledgment

NA is supported by the Wellcome Trust

Authors’ Affiliations

(1)
University College London, Bloomsbury Institute of Intensive Care Medicine, London, UK
(2)
University College London, Centre for Nephrology, London, UK
(3)
Imperial College London, Department of Nephrology, London, UK
(4)
Major Hospital Niguarda Ca Granda, Intensive Care Medicine, Milan, Italy

Copyright

© Arulkumaran et al; licensee Springer. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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