First, we demonstrate that renal FGFR4 expression is highly regulated in CKD and α-klotho deficiency, suggesting that impaired renal function or the uremic milieu consisting of hyperphosphatemia, elevated serum FGF23 levels, α-klotho deficiency or increased oxidative stress directly contribute to the downregulation of FGFR4. Here, FGFR4 is linked to hyperphosphatemia.