Our data in this study clearly indicated that decreased expressions of Klotho, p-ERK1/2 and SGK1 and increased expressions of FGFR1, NHERF-1 and NaPi-2a in the kidneys of the CKD–MBD model rats and the cultured NRK-52E cells exposed to TGF-β and rFGF23 were obviously revealed, respectively, in the meantime, concomitant with increased serum P4+ (hyperphosphatemia), decreased urine P4+, increased serum FGF23 and osteoporosis-like pathological lesions in the femur bone. Here, NHERF1 is linked to hyperphosphatemia.