Evaluation of cerium oxide as a phosphate binder using 5/6 nephrectomy model rat

Background: The number of chronic kidney disease (CKD) patients continues to increase worldwide. CKD patients need to take phosphate binders to manage serum phosphorus concentrations. Currently, several types of phosphate binder, including lanthanum carbonate, are used. However, they each have disadvantages. Methods: In this study, we evaluated cerium oxide as a new phosphate binder in vitro and in vivo. First, cerium oxide was mixed with phosphoric acid at pH 2.5 or 7.0, and residual phosphoric acid was measured by absorption photometry using colorimetric reagent. Second, cerium oxide was fed to 5/6 nephrectomy model rats (5/6Nx), a well-known renal damage model. All rats were measured food intake, water intake, feces volume, and urine volume, and collected serum and urine were analyzed for biochemical markers. Results: Cerium oxide can adsorb phosphate at acidic and neutral pH, while lanthanum carbonate, which is a one of popular phosphate binder, does not dissolve at neutral pH. Cerium oxide-treatment reduced serum phosphate concentrations of 5/6Nx rats without an increase in serum alanine transaminase levels that would indicate hepatotoxicity, and cerium oxide-treatment maintained serum creatinine and blood urea nitrogen levels, while those of normal 5/6Nx rats increased slightly. Conclusions: These results suggest that cerium oxide can be a potential phosphate binder. Decreased body weight gain and increased water intake and urine volume in 5/6Nx rats were thought to be an effect of nephrectomy because these changes did not occur in sham operation rats. Additional investigations are needed to evaluate the longer-term safety and possible accumulation of cerium oxide in the body.