Presentation description

Chronic kidney disease (CKD) affects over 37 million adults in the United States and is heavily influenced by dietary and metabolic factors. Most rodent models of CKD rely on surgical or chemical insults, which do not reflect the slow, progressive nature of human disease. To address this, we evaluated whether a high fat, high salt (HF/HNa) diet could induce kidney dysfunction in C57Bl/6J and C57Bl/6N mice, two commonly used models in metabolic research. Mice were fed either standard chow or a HF/HNa diet (42% fat, 8% sodium chloride) for 16 weeks. Physiological assessments included glomerular filtration rate (GFR) by FITC-Sinistrin clearance, 24-hour urine collection, NMR-based body composition, and Western blot analysis of kidney proteins.

Body weight did not significantly differ between groups, likely due to the high salt content reducing food intake in HF/HNa-fed mice. Interestingly, 6J mice, but not 6N mice, exhibited lower GFR on the HF/HNa diet, consistent with increases in urinary albumin-to-creatinine ratio. However, only 6N mice exhibited increased AQP2 and decreased SGLT2 protein abundance, suggesting an adaptive renal response to maintain electrolyte balance through decreased salt reabsorption and increased water absorption. These findings offer novel insight into high-salt-induced renal dysfunction and highlight mechanisms by which dietary salt contributes to a decline in renal function in a murine model of CKD.