Animal models of renal dysfunction: acute kidney injury

Abstract

Background: Acute renal failure (ARF) is a broad clinical entity, encompassing diverse pathophysiologies, with heterogeneous functional and morphological features. In the same fashion, various animal models of ARF differ in their mechanisms, distribution and type of injury, cellular responses and outcome. Objective: To appraise available animal models of ARF used for the assessment of potential therapeutic interventions, providing their basic pathophysiologies. Methods: Review of literature and summaries of expert opinion discussion forums. Results/conclusions: Various animal models of ARF are used for the development of therapeutic/preventive interventions, including toxic, hypoxic and septic models. Incomplete understanding of the outstanding complexity of human ARF often leads to too simplistic interventional concepts or to misconceptions, based on models with limited clinical relevance. Thus, for the appropriateness of animal models, the use of models inflicting severe injury, though highly reproducible and consistent, should be weighted against more clinically relevant models. Such models often consist of milder insults, supplemented with the induction of predisposing factors or supportive measures, encountered in the clinical practice. In the perspective of the compound pathogenesis of ARF, assessment of the degree of renal dysfunction is not enough as a single end point, and should be complemented by the evaluation of parameters such as renal microcirculation, oxygenation, cellular adaptive response and morphology. New imaging technologies and biomarkers bring about new insight in this evolving field.

Keywords::

• acute
• amphotericin
• cisplatin
• contrast media
• gentamicin
• glycerol
• hypoxia
• kidney
• kidney failure
• non-steroidal anti-inflammatory agents
• rhabdomyolyisis
• sepsis