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Acute Kidney Injury Models

Creative Animodel is a global contract research organization (CRO) specializing in offering a set of preclinical in vivo pharmacology services based on our disease models. Our staffs consist of highly qualified and experienced pharmaceutical industry research professionals who have demonstrated success in advancing projects from preclinical to Phase III clinical trials.

What Is Acute Kidney Injury?

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Acute kidney injury (AKI), also known as acute renal failure (ARF) or acute kidney failure (AKF), is a broad clinical entity, encompassing diverse and often overlapping pathophysiologies. It is characterized by a rapid, potentially reversible, decline in renal function including rapid fall in glomerular filtration rate (GFR) and retention of nitrogenous waste products over a period of hours or days. Clinically, AKI can be conveniently divided into pre-renal, renal (intrinsic) and post-renal failure. Pre-renal AKI is caused by decrease of effective blood volume, causing a reduction in GFR. Intrinsic kidney injury occurs when there is a
damage to the structures of the nephron such as the glomeruli, tubules, vessels, or interstitium. Post-renal AKI follows obstruction of the urinary collection system with an increase in pressure within the renal collecting systems resulting in reduced GFR and renal failure. It is also a frequent threatening complication following trauma, complex surgical procedures, and in patients hospitalized in intensive care units. As so far, the mortality rate of patients with AKI has remained 25–70% despite the use of various pharmacologic agents.

AKI Models Provided by Creative Animodel

A variety of animal models of AKI have been developed to match the diversity and complexity of the human condition. In order to understand the underlying pathogenic mechanisms in different AKI in conditions and to explore the drug therapeutics, Creative Animodel has established various AKI models.

Uni-nephrectomy model:
Uni-nephrectomy model has been developed as a model of acute ischemia-induced renal injury by contra lateral nephrectomy. It can reproduce the features of human ischemia induced acute kidney injury in animals.

Gentamicin-induced model:
Gentamicin is widely used antibiotics for the treatment of Gram negative infections. However, the high dose of gentamicin has been shown to produce nephrotoxicity. By repeat administration of gentamicin sulfate, Creative Animodel has successfully established gentamicin-induced AKI model that mimics the nephrotoxicity-induced changes in renal function in clinical setup.

LPS-induced model:
Endotoxin administration is widely used for sepsis models. Sepsis-induced renal impairment is related to systemic inflammatory response and endothelial dysfunction. By intravenous infusion of lipopolysaccharide (LPS), we have established sepsis-induced models of AKI which can mimic the infection-induced renal failure in humans.

Pharmacology Evaluation

In clinical point of view, acute kidney injury is mainly caused by ischemic factors, nephrotoxicity as well as sepsis. At Creative Animodel, we have successfully established various AKI models that mimic those conditions. Besides, we provide associated preclinical services to evaluate the efficacy and safety of your novel therapeutics based on our AKI models, including but not limited to:      
• Complete blood count (CBC)
• Serum biochemistries
• Urea analysis: microscopy, electrolytes and nitrogen analysis
• Kidney biopsy
• Other parameters: renal microcirculation, oxygenation, cellular adaptive response and morphology

Creative Animodel provides a full range of preclinical in vivo pharmacology services based on our AKI models. With extensive expertise, our scientists can offer clients the most comprehensive supports for their programs development. If you have any questions, please feel free to contact us.

Reference:
1. Singh A P.; et al. Animal models of acute renal failure[J]. Pharmacological Reports, 2012, 64(1): 31-44.

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