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

Martin A Schick,Christopher Held,Norbert Roewer,Robert W Brock,Reinhard Schneider,Jakob Wollborn,Nicolas Schlegel,Wolfgang Baar,Sven Flemming,Christian Wunder

doi:10.1186/s40635-014-0034-x

Abstract

BackgroundUp 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.MethodsAnaesthetized 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.ResultsAll 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.ConclusionsThe 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.

Highlights

Up to 50% of septic patients develop acute kidney injury (AKI)
Our described method may serve as a new standard for experimental investigations of septic AKI
All animals survived, revealed mean arterial pressure (MAP) > 70 mmHg during 24 h and showed no abscess formation at the end of the experiments. standardized colon ascendens stent peritonitis (sCASP)-treated animals displayed clinical features of illness and showed ubiquitous peritonitis and significantly increased sepsis signs after 24 h including a decrease in activity, reduced alertness, ruffled fur, and hunched posture

Summary

Introduction

Up to 50% of septic patients develop acute kidney injury (AKI). The pathomechanism of septic AKI is poorly understood. 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. Acute kidney injury (AKI) is common and imposes a heavy burden of illness (morbidity and mortality) [1]. Thirty to fifty percent of septic patients develop renal failure, and AKI can double the mortality rate up to 70%. An ideal AKI animal sepsis model should base upon (a) standardized focus of infection as a septic origin in a clinical setting [4], (b) invasive monitoring of macrohaemodynamics, (c) investigation of RBF with following renal function tests, (d) histopathology and (e) feasible reproducibility

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