Folic acid-induced animal model of kidney disease

The kidneys are a vital organ that is vulnerable to both acute kidney injury (AKI) and chronic kidney disease (CKD) which can be caused by numerous risk factors such as ischemia, sepsis, drug toxicity and drug overdose, exposure to heavy metals, and diabetes. In spite of the advances in our understanding of the pathogenesis of AKI and CKD as well AKI transition to CKD, there is still no available therapeutics that can be used to combat kidney disease effectively, highlighting an urgent need to further study the pathological mechanisms underlying AKI, CKD, and AKI progression to CKD. In this regard, animal models of kidney disease are indispensable. This article reviews a widely used animal model of kidney disease, which is induced by folic acid (FA). While a low dose of FA is nutritionally beneficial, a high dose of FA is very toxic to the kidneys. Following a brief description of the procedure for disease induction by FA, major mechanisms of FA-induced kidney injury are then reviewed, including oxidative stress, mitochondrial abnormalities such as impaired bioenergetics and mitophagy, ferroptosis, pyroptosis, and increased expression of fibroblast growth factor 23 (FGF23). Finally, application of this FA-induced kidney disease model as a platform for testing the efficacy of a variety of therapeutic approaches is also discussed. Given that this animal model is simple to create and is reproducible, it should remain useful for both studying the pathological mechanisms of kidney disease and identifying therapeutic targets to fight kidney disease.