Animal models of kidney inflammation in translational medicine

• Animal models remain an important experimental tool in translational medicine.
• Simple single shot models can be used to explore new targets in kidney research.
• Inducible, transgene, or gene knockout models are used to study particular disease mechanisms.
• Preclinical drug testing requires models that mimic human disease in all aspects.
• As this is difficult in multigenic disorders, several models are needed to increase predictability.

Animal models remain an important experimental tool in translational medicine albeit being often criticized for their poor value to mimic human pathophysiology and to predict treatment efficacy. Translational medicine is a multistep process and choosing animal models follows different criteria at each of these stages. Initially, target expression and function are tested in simple models of kidney injury that may or may not mimic any corresponding human disorder. Inappropriate overinterpretation of results from such studies is common. When promising targets are further studied in more specific disease contexts, it becomes necessary to apply animal models that more closely mimic human disease. In general, animal models of monogenetic disorders meet this requirement at best. Polygenic or multicausal disorders like acute kidney injury, glomerulonephritis, focal segmental glomerulosclerosis, and diabetic nephropathy are already extremely heterogeneous in humans and often share nothing else but a characteristic histopathological lesion. When selecting animal models simply for histopathological lesions the heterogeneity of upstream molecular pathways is ignored resulting in poor predictability for human disease. In this setting, consistent data obtained from multiple disease models involving different upstream disease mechanisms can improve predictability. Furthermore, using animal models in different species reduces the risk of species-specific limitations. In this review we discuss these aspects by focusing on animal models of kidney inflammation.