Oxalate-induced chronic kidney disease with its uremic and cardiovascular complications in C57BL/6 mice

Area of Science:

• Nephrology
• Animal Models
• Toxicology

Background:

• Chronic kidney disease (CKD) research is hindered by the absence of practical inducible animal models that replicate human disease and its complications.
• Existing models often fail to fully capture the complexity of CKD progression and associated pathologies.

Purpose of the Study:

• To establish a novel, inducible mouse model for chronic kidney disease (CKD) that accurately mimics human disease characteristics and complications.
• To validate the utility of this model for studying CKD pathogenesis and potential therapeutic interventions.

Main Methods:

• Induction of CKD in C57BL/6 mice using a soluble oxalate-rich diet.
• Assessment of renal histology, including tubular damage, glomerular changes, inflammation, and fibrosis.
• Analysis of gene expression markers and magnetic resonance imaging (MRI) for inflammation and fibrosis.
• Monitoring of physiological parameters such as anemia, metabolic acidosis, electrolyte balance, and hypertension.

Main Results:

• The oxalate-rich diet successfully induced stable stages of CKD in both male and female mice.
• Histological analysis revealed dose-dependent tubular damage, interstitial inflammation, fibrosis, and glomerular obsolescence.
• Mice developed key CKD complications within 3 weeks, including anemia, metabolic acidosis, hyperkalemia, hyperphosphatemia, hyperparathyroidism, and FGF23 activation.
• The model exhibited persistent arterial hypertension and cardiac fibrosis, even after dietary intervention.

Conclusions:

• A novel, diet-inducible mouse model for CKD has been successfully established, closely mirroring human disease features.
• This model overcomes limitations of previous experimental systems and provides a robust platform for investigating CKD and its multifaceted complications.
• The model's ability to induce progressive renal and cardiovascular pathology makes it highly valuable for preclinical research and drug development in nephrology.