**2.2 Phosphate metabolism in hemodialysis patients**

Several studies have measured circulating FGF23 levels in predialysis and dialysis patients and reported progressively elevated FGF23 levels as serum creatinine or phosphate levels increase (Larsson et al., 2003; Imanishi et al., 2004). Thus, it appears that in patients with CKD, FGF23 production increases to counteract chronic phosphate retention by promoting urinary phosphate excretion in the face of reduced nephron mass. Notably, in this setting, a previous study showed that FGF23 was a strong independent predictor of diminished 1,25(OH)2D levels, even after adjustment for renal function, serum phosphorus levels and 25(OH)D levels (Gutierrez et al., 2005). This finding suggests that in patients with CKD, increases in FGF23 intended to maintain neutral phosphate balance result in suppression of renal 1,25(OH)2D production, thereby triggering the early development of secondary hyperparathyroidism (Fig. 1).
