Context. Nephrolithiasis affects about 10% of the population in industrialised countries with calcium salts composing more than 80% of renal stones. A significant percentage of patients with calcium nephrolithiasis and normal parathyroid function show hypophosphataemia and reduced renal phosphate reabsorption (i.e. a renal phosphate leak).

Objectives. To compare serum levels of fibroblast growth factor 23 (FGF23), a regulator of phosphate homeostasis, in 110 recurrent stone formers with or without renal phosphate leak, 6 patients affected by X-linked hypophosphataemic rickets, 5 patients affected by oncogenic osteomalacia and 60 unrelated healthy controls.

Design. Prospective interventional study.

Methods. Renal phosphate leak was identified based on the occurrence of idiopathic hypophosphataemia (serum phosphate concentration <2.50 mg/dl (<0.80 mmol/liter)), and reduced renal threshold phosphate concentration (<2.2 mg/liter (<0.70 mmol/liter)).

Results. In 22 stone formers with renal phosphate leak, serum FGF23 concentration was significantly higher as compared with 88 stone formers without renal phosphate leak and with controls (83.3 (65.6-101.1) vs. 32.1 (26.8-37.4) and 24.5 (19.8-29.1) RU/ml respectively). Stone formers with renal phosphate leak showed lower FGF23 compared with patients with oncogenic osteomalacia and X-linked hypophosphataemic rickets (572.3 (235.9-908.7) RU/ml). Among stone formers and controls, serum FGF23 concentration displayed a strong inverse association with serum phosphate (r0.784, P = 0.009) and with the rate of tubular phosphate reabsorption (r0.791, P = 0.008).

Conclusions. In our study population, renal phosphate leak affected 20% of stone formers and was strongly associated with increased serum FGF23 concentration.