Cargando…

Sepsis-induced acute kidney injury by standardized colon ascendens stent peritonitis in rats - a simple, reproducible animal model

BACKGROUND: Up to 50% of septic patients develop acute kidney injury (AKI). The pathomechanism of septic AKI is poorly understood. Therefore, we established an innovative rodent model to characterize sepsis-induced AKI by standardized colon ascendens stent peritonitis (sCASP). The model has a standa...

Descripción completa

Detalles Bibliográficos
Autores principales: Schick, Martin A, Baar, Wolfgang, Flemming, Sven, Schlegel, Nicolas, Wollborn, Jakob, Held, Christopher, Schneider, Reinhard, Brock, Robert W, Roewer, Norbert, Wunder, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer International Publishing 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4513002/
https://www.ncbi.nlm.nih.gov/pubmed/26266931
http://dx.doi.org/10.1186/s40635-014-0034-x
_version_ 1782382572224905216
author Schick, Martin A
Baar, Wolfgang
Flemming, Sven
Schlegel, Nicolas
Wollborn, Jakob
Held, Christopher
Schneider, Reinhard
Brock, Robert W
Roewer, Norbert
Wunder, Christian
author_facet Schick, Martin A
Baar, Wolfgang
Flemming, Sven
Schlegel, Nicolas
Wollborn, Jakob
Held, Christopher
Schneider, Reinhard
Brock, Robert W
Roewer, Norbert
Wunder, Christian
author_sort Schick, Martin A
collection PubMed
description BACKGROUND: Up to 50% of septic patients develop acute kidney injury (AKI). The pathomechanism of septic AKI is poorly understood. Therefore, we established an innovative rodent model to characterize sepsis-induced AKI by standardized colon ascendens stent peritonitis (sCASP). The model has a standardized focus of infection, an intensive care set up with monitoring of haemodynamics and oxygenation resulting in predictable impairment of renal function, AKI parameters as well as histopathology scoring. METHODS: Anaesthetized rats underwent the sCASP procedure, whereas sham animals were sham operated and control animals were just monitored invasively. Haemodynamic variables and blood gases were continuously measured. After 24 h, animals were reanesthetized; cardiac output (CO), inulin and PAH clearances were measured and later on kidneys were harvested; and creatinine, urea, cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) were analysed. Additional sCASP-treated animals were investigated after 3 and 9 days. RESULTS: All sCASP-treated animals survived, whilst ubiquitous peritonitis and significantly deteriorated clinical and macrohaemodynamic sepsis signs after 24 h (MAP, CO, heart rate) were obvious. Blood analyses showed increased lactate and IL-6 levels as well as leucopenia. Urine output, inulin and PAH clearance were significantly decreased in sCASP compared to sham and control. Additionally, significant increase in cystatin C and NGAL was detected. Standard parameters like serum creatinine and urea were elevated and sCASP-induced sepsis increased significantly in a time-dependent manner. The renal histopathological score of sCASP-treated animals deteriorated after 3 and 9 days. CONCLUSIONS: The presented sCASP method is a standardized, reliable and reproducible method to induce septic AKI. The intensive care set up, continuous macrohaemodynamic and gas exchange monitoring, low mortality rate as well as the opportunity of detailed analyses of kidney function and impairments are advantages of this setup. Thus, our described method may serve as a new standard for experimental investigations of septic AKI.
format Online
Article
Text
id pubmed-4513002
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Springer International Publishing
record_format MEDLINE/PubMed
spelling pubmed-45130022015-07-27 Sepsis-induced acute kidney injury by standardized colon ascendens stent peritonitis in rats - a simple, reproducible animal model Schick, Martin A Baar, Wolfgang Flemming, Sven Schlegel, Nicolas Wollborn, Jakob Held, Christopher Schneider, Reinhard Brock, Robert W Roewer, Norbert Wunder, Christian Intensive Care Med Exp Research BACKGROUND: Up to 50% of septic patients develop acute kidney injury (AKI). The pathomechanism of septic AKI is poorly understood. Therefore, we established an innovative rodent model to characterize sepsis-induced AKI by standardized colon ascendens stent peritonitis (sCASP). The model has a standardized focus of infection, an intensive care set up with monitoring of haemodynamics and oxygenation resulting in predictable impairment of renal function, AKI parameters as well as histopathology scoring. METHODS: Anaesthetized rats underwent the sCASP procedure, whereas sham animals were sham operated and control animals were just monitored invasively. Haemodynamic variables and blood gases were continuously measured. After 24 h, animals were reanesthetized; cardiac output (CO), inulin and PAH clearances were measured and later on kidneys were harvested; and creatinine, urea, cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) were analysed. Additional sCASP-treated animals were investigated after 3 and 9 days. RESULTS: All sCASP-treated animals survived, whilst ubiquitous peritonitis and significantly deteriorated clinical and macrohaemodynamic sepsis signs after 24 h (MAP, CO, heart rate) were obvious. Blood analyses showed increased lactate and IL-6 levels as well as leucopenia. Urine output, inulin and PAH clearance were significantly decreased in sCASP compared to sham and control. Additionally, significant increase in cystatin C and NGAL was detected. Standard parameters like serum creatinine and urea were elevated and sCASP-induced sepsis increased significantly in a time-dependent manner. The renal histopathological score of sCASP-treated animals deteriorated after 3 and 9 days. CONCLUSIONS: The presented sCASP method is a standardized, reliable and reproducible method to induce septic AKI. The intensive care set up, continuous macrohaemodynamic and gas exchange monitoring, low mortality rate as well as the opportunity of detailed analyses of kidney function and impairments are advantages of this setup. Thus, our described method may serve as a new standard for experimental investigations of septic AKI. Springer International Publishing 2014-12-09 /pmc/articles/PMC4513002/ /pubmed/26266931 http://dx.doi.org/10.1186/s40635-014-0034-x Text en © Schick et al.; licensee Springer. 2014 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.
spellingShingle Research
Schick, Martin A
Baar, Wolfgang
Flemming, Sven
Schlegel, Nicolas
Wollborn, Jakob
Held, Christopher
Schneider, Reinhard
Brock, Robert W
Roewer, Norbert
Wunder, Christian
Sepsis-induced acute kidney injury by standardized colon ascendens stent peritonitis in rats - a simple, reproducible animal model
title Sepsis-induced acute kidney injury by standardized colon ascendens stent peritonitis in rats - a simple, reproducible animal model
title_full Sepsis-induced acute kidney injury by standardized colon ascendens stent peritonitis in rats - a simple, reproducible animal model
title_fullStr Sepsis-induced acute kidney injury by standardized colon ascendens stent peritonitis in rats - a simple, reproducible animal model
title_full_unstemmed Sepsis-induced acute kidney injury by standardized colon ascendens stent peritonitis in rats - a simple, reproducible animal model
title_short Sepsis-induced acute kidney injury by standardized colon ascendens stent peritonitis in rats - a simple, reproducible animal model
title_sort sepsis-induced acute kidney injury by standardized colon ascendens stent peritonitis in rats - a simple, reproducible animal model
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4513002/
https://www.ncbi.nlm.nih.gov/pubmed/26266931
http://dx.doi.org/10.1186/s40635-014-0034-x
work_keys_str_mv AT schickmartina sepsisinducedacutekidneyinjurybystandardizedcolonascendensstentperitonitisinratsasimplereproducibleanimalmodel
AT baarwolfgang sepsisinducedacutekidneyinjurybystandardizedcolonascendensstentperitonitisinratsasimplereproducibleanimalmodel
AT flemmingsven sepsisinducedacutekidneyinjurybystandardizedcolonascendensstentperitonitisinratsasimplereproducibleanimalmodel
AT schlegelnicolas sepsisinducedacutekidneyinjurybystandardizedcolonascendensstentperitonitisinratsasimplereproducibleanimalmodel
AT wollbornjakob sepsisinducedacutekidneyinjurybystandardizedcolonascendensstentperitonitisinratsasimplereproducibleanimalmodel
AT heldchristopher sepsisinducedacutekidneyinjurybystandardizedcolonascendensstentperitonitisinratsasimplereproducibleanimalmodel
AT schneiderreinhard sepsisinducedacutekidneyinjurybystandardizedcolonascendensstentperitonitisinratsasimplereproducibleanimalmodel
AT brockrobertw sepsisinducedacutekidneyinjurybystandardizedcolonascendensstentperitonitisinratsasimplereproducibleanimalmodel
AT roewernorbert sepsisinducedacutekidneyinjurybystandardizedcolonascendensstentperitonitisinratsasimplereproducibleanimalmodel
AT wunderchristian sepsisinducedacutekidneyinjurybystandardizedcolonascendensstentperitonitisinratsasimplereproducibleanimalmodel