Calcium oxalate crystal deposition in metabolic syndrome model rat kidneys

Objective: Although an epidemiological link between the metabolic syndrome and kidney stone formation has been reported, the mechanism by which metabolic syndrome promotes kidney stone formation has yet to be elucidated. We investigated calcium oxalate (CaOx) kidney stone formation in a rat metabolic syndrome model. Methods: We induced hyperoxaluria in 8‐week‐old male Otsuka Long‐Evans Tokushima fatty (OLETF) rats, and a control strain, Long‐Evans Tokushima Otsuka (LETO) rats, by administering 1.0% ethylene glycol (EG) as their drinking water for 2 weeks. Rats were divided into four groups: LETO‐C (control, n = 7); LETO‐SF (stone forming, n = 8); OLETF‐C (n = 7); and OLETF‐SF (n = 8). Urine and blood samples were collected for biochemistry testing, and the kidneys were harvested for estimation of crystal deposition and determinations of the expression of osteopontin (OPN) and monocyte chemoattractant protein‐1 (MCP‐1). Results: Administration of EG induced hyperoxaluria to the same degree in both strains. The OLETF‐SF group showed a higher grade of renal crystal deposition and significantly higher renal calcium content than the LETO‐SF group. Although the OLETF‐C group excreted significantly higher amounts of uric acid and more acidic urine than the LETO‐C group, similar differences were not observed in rats given EG. Significant upregulation of both OPN and MCP‐1 was seen in the kidneys of hyperoxaluric rats, with higher levels of expression in the OLETF‐SF group than the LETO‐SF group. Conclusions: The present results show for the first time that OLETF rats form more renal CaOx crystal deposits compared with control rats under EG‐induced hyperoxaluric conditions. The model described here should be useful for investigating the mechanisms by which the metabolic syndrome promotes CaOx kidney stone formation.