Animal Models of Kidney Disease: Challenges and Perspectives

Abstract

Kidney disease is highly prevalent and affects about 850 million people worldwide. It is also associated with high morbidity and mortality, and current therapies are incurable and often ineffective. Animal models are indispensable for understanding the pathophysiology of various kidney diseases and for preclinically testing novel remedies. In the last two decades, rodents continue to be the most used models for imitating human kidney diseases, largely due to the increasing availability of many unique genetically modified mice. Despite many limitations and pitfalls, animal models play an essential and irreplaceable role in gaining novel insights into the mechanisms, pathologies and therapeutic targets of kidney disease. In this review, we highlight commonly used animal models of kidney diseases by focusing on experimental acute kidney injury, chronic kidney disease, and diabetic kidney disease. We briefly summarize the pathological characteristics, advantages and drawbacks of some widely used models. Emerging animal models such as mini-pig, salamander, zebrafish and drosophila, as well as human-derived kidney organoids and kidney-on-a-chip are also discussed. Undoubtedly, careful selection and utilization of appropriate animal models is of vital importance in deciphering the mechanisms underlying nephropathies and evaluating the efficacy of new treatment options. Such studies will provide a solid foundation for future diagnosis, prevention and treatment of human kidney diseases.

Klotho-derived peptide 1 inhibits cellular senescence in the fibrotic kidney by restoring Klotho expression via posttranscriptional regulation

“…Animal studies were approved by the Animal Ethics Committee at the Nanfang Hospital, Southern Medical University. Male C57BL/6 mice aged 8-10 weeks were purchased from Beijing Vital River Laboratory Animal Technology Co. For UUO model, mice were anesthetized and their left ureter ligated 27 . The sham group underwent exposure of the left kidney without ligation of the ureter.…”

Myeloid-derived Wnts play an indispensible role in macrophage and fibroblast activation and kidney fibrosis

“…All animals were born normally at the expected Mendelian frequency, and they were normal in size and did not display any gross physical or behavioral abnormalities. Male mice at age of 8 weeks, approximately 22-25g in weight, were then subjected to UUO and UIRI by using established procedures, as described elsewhere 38 , 39 . Mice were sacrificed at day 7 after UUO.…”

m6A RNA methylation drives kidney fibrosis by upregulating β-catenin signaling

“…Male C57BL/6 mice were obtained from the Experimental Animal Center of Southern Medical University. Unilateral ischemia-reperfusion injury (UIRI) and unilateral ureteral obstruction (UUO) models were established according to routine protocols 8 , 28 , 29 .…”