Animal model of kidney disease induced by high folic acid

Purpose: The kidney is a vital organ that helps the body eliminate waste and toxic substances and return nutrients and vital substances back into the bloodstream. Kidney disease can be categorized into acute kidney injury (AKI) or chronic kidney disease (CKD). This may be caused by numerous risk factors such as ischemia, sepsis, drug toxicity and drug overdose, exposure to heavy metals, and diabetes. However, the exact prognosis from an AKI to CKD is not fully understood. In addition, approximately 37 million individuals in the United States population currently suffer from CKD. Despite the high prevalence of CKD, information is lacking on our understanding of the pathogenesis of AKI and CKD and there are still no available therapeutics that can be used to combat kidney disease effectively. This highlights 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 imperative.

Methods: This presentation reviews a widely used animal model of kidney disease, which is induced in mice with folic acid (FA). While a low dose of FA is nutritionally favorable, a high dose of FA is toxic to the kidneys. A high dose of FA is injected intra-peritoneally in the mice. Following a brief description of the procedure for disease induction by FA, major mechanisms of FA-induced kidney injury are then reviewed. This includes observing oxidative stress levels, mitochondrial abnormalities such as impaired bioenergetics and mitophagy, ferroptosis, pyroptosis, and increased expression of fibroblast growth factor 23 (FGF23). This is completed to explore possible pathological mechanisms of kidney disease and thereby the efficacy of a variety of therapeutic approaches may be evaluated. These procedural methods required Institutional Animal Care and Use Committee (IACUC) clearance and proper laboratory training to ensure ethical laboratory practices. The presentation will also highlight an overview of how to obtain IACUC clearance and ethical practice certification.

Results: This animal model of inducing high doses of FA can induce both AKI and CKD in mice and therefore can be used to further study AKI to CKD progression.

Conclusion: Given that the animal model is reproducible and can recapitulate human kidney disease phenotypes, it should be useful for both studying the pathological mechanisms of kidney disease and identifying effective therapeutic targets to fight kidney disease.

This presentation is supported by PDRT at UNTHSC