Fibroblast growth factor 23 mediates the phosphaturic actions of cadmium

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Phosphaturia has been documented following cadmium (Cd) exposure in bothhumans and experimental animals. The fibroblast growth factor 23 (FGF23)/klotho axisserves as an essential phosphate homeostasis pathway in the bone-kidney axis. In the presentstudy, we investigated the effects of Cd on phosphate (Pi) homeostasis in mice. FollowingCd injection into WT mice, plasma FGF23 concentration was significantly increased.Urinary Pi excretion levels were significantly higher in Cd-injected WT mice than in controlgroup. Plasma Pi concentration decreased only slightly compared with control group.No change was observed in plasma parathyroid hormone and 1,25-dihydroxy vitamin D3in both group of mice. We observed a decrease in phosphate transport activity and alsodecrease in expression of renal phosphate transporter SLC34A3 [NaPi-IIc/NPT2c], butnot SLC34A1 [NaPi-IIa/NPT2a]. Furthermore, we examined the effect of Cd on Npt2c inNpt2a-knockout (KO) mice which expresses Npt2c as a major NaPi co-transporter. InjectingCd to Npt2aKO mice induced significant increase in plasma FGF23 concentration andurinary Pi excretion levels. Furthermore, we observed a decrease in phosphate transportactivity and renal Npt2c expression in Cd-injected Npt2a KO mice. The present study suggeststhat hypophosphatemia induced by Cd may be closely associated with the FGF23/klotho axis.