Background: Up to 50% of septic patients develop acute kidney injury (AKI). The\npathomechanism of septic AKI is poorly understood. Therefore, we established an\ninnovative rodent model to characterize sepsis-induced AKI by standardized colon\nascendens stent peritonitis (sCASP). The model has a standardized focus of\ninfection, an intensive care set up with monitoring of haemodynamics and\noxygenation resulting in predictable impairment of renal function, AKI parameters\nas well as histopathology scoring.\nMethods: Anaesthetized rats underwent the sCASP procedure, whereas sham\nanimals were sham operated and control animals were just monitored invasively.\nHaemo dynamic variables and blood gases were continuously measured. After 24 h,\nanimals were reanesthetized; cardiac output (CO), inulin and PAH clearances\nwere measured and later on kidneys were harvested; and creatinine, urea,\ncystatin C and neutrophil gelatinase-associated lipocalin (NGAL) were analysed.\nAdditional sCASP-treated animals were investigated after 3 and 9 days.\nResults: All sCASP-treated animals survived, whilst ubiquitous peritonitis and\nsignificantly deteriorated clinical and macrohaemodynamic sepsis signs after 24 h\n(MAP, CO, heart rate) were obvious. Blood analyses showed increased lactate\nand IL-6 levels as well as leucopenia. Urine output, inulin and PAH clearance\nwere significantly decreased in sCASP compared to sham and control. Additionally,\nsignificant increase in cystatin C and NGAL was detected. Standard parameters like\nserum creatinine and urea were elevated and sCASP-induced sepsis increased\nsignificantly in a time-dependent manner. The renal histopathological score of\nsCASP-treated animals deteriorated after 3 and 9 days.\nConclusions: The presented sCASP method is a standardized, reliable and\nreproducible method to induce septic AKI. The intensive care set up, continuous\nmacrohaemodynamic and gas exchange monitoring, low mortality rate as well\nas the opportunity of detailed analyses of kidney function and impairments are\nadvantages of this setup. Thus, our described method may serve as a new\nstandard for experimental investigations of septic AKI.
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