Animal models are essential for exploring acute renal failure (ARF) and the development of effective therapy for its optimal management. At Bienta we utilize several rodent models to mimic the clinical conditions of renal failure.
Cisplatin-induced acute kidney injury. Cisplatin is a widely used anticancer drug accompanied by adverse side effects, including toxin-induced acute kidney injury (AKI). Intraperitoneal administration of 10–12 mg/kg Cisplatin results in cellular uptake and efflux, apoptosis, vascular injury, oxidative and endoplasmic reticulum stress, and inflammation within 72 hours, followed by a slow recovery phase for 7 days. The severity of the pathology depends on the dose administered.
Lipopolysaccharide (LPS) induced acute kidney injury. LPS is a potent inducer of inflammation. Parenteral administration of LPS causes the production of a wide range of proinflammatory cytokines and is used as a model of sepsis. The inflammatory process also leads to hemodynamic changes and acute kidney injury. Intraperitoneal administration of 10 mg/kg LPS results in sepsis-associated acute renal damage within 24-72 hours. This is a rapid acute model, lasting 72-96 hours.
Gentamicin-induced acute kidney injury in rats Gentamicin is a broad-spectrum antibiotic with side effects of toxin-induced acute kidney injury. Intraperitoneal administration of 100 mg/kg Gentamicin for four consecutive days results in renal tubular damage in rats, followed by a slow recovery phase for 14 days. The severity of the pathology depends on the dose administered.
Renal ischemia-reperfusion injury model in rats The Renal ischemia-reperfusion injury model (IRI) is achieved by applying ischemia on the kidney by clamping the renal artery and vein. Typically, renal vascular clamping for 50 minutes is used to induce renal injury, followed by reperfusion. The ischemia-reperfusion procedure leads to an acute decrease in renal function, uncovered by the level of urea and creatinine in the blood.
Renal unilateral ischemia-reperfusion injury followed by contralateral nephrectomy model in mice.
The Renal ischemia-reperfusion injury model (IRI) is achieved by applying ischemia on the kidney to induce acute kidney injury by clamping the renal artery and vein. CD-1 mice undergo renal pedicle clamping for 35-40 min followed by contralateral nephrectomy 7 days after the injury. Early post-injury tubular damage as well as post-injury fibrosis, are highly consistent using this model.
Service details: A standard study design includes at least 2 groups of male CD-1 mice (vehicle dosed and treated with tested compound), 7 days of acclimatization period, one day IRI procedure, 7 days of post-injury recovery, 1 day for contralateral nephrectomy, and 7-10 days of the observation period. Treatment with drugs is possible in periods both before the injury to reduce the development of pathological processes and after the injury to improve the recovery. Animals are observed for mortality, body weight changes, and signs of toxicity daily for all treatment and post-treatment periods. Clinical chemistry parameters of renal failure (creatinine and urea in the blood) and NGAL levels in the blood can be determined over the time of the observation period. A gross necropsy is performed on all animals at the endpoint. Specific tests, such as hematological, urinary, and blood clinical chemistry analysis, food and water intake, histopathology, etc., in combination with more definitive toxic or gross pathology endpoints, are available on request.