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Fibroblast Growth Factor 23 Is Increased in Calcium Nephrolithiasis with Hypophosphatemia and Renal Phosphate Leak

Department of Clinical and Experimental Medicine (D.R., G.M., P.S.), Federico II University Medical School, 80131 Naples, Italy; Unit of Pediatric Endocrinology (G.D.F.), Azienda Ospedaliera di Rilievo Nazionale "G. Rummo," 82100 Benevento, Italy; and Department of General Pathology (M.C.), Second University of Naples, 80121 Naples, Italy

Address all correspondence and requests for reprints to: Giuseppe Mossetti, Dipartimento di Medicina Clinica e Sperimentale, Università Federico II, Via S. Pansini, 5-80131 Naples, Italy. E-mail: giumosse{at}unina.it.

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

Objectives: The objective of the study was 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, six patients affected by X-linked hypophosphatemic rickets, five patients affected by oncogenic osteomalacia, and 60 unrelated healthy controls.

Design: This was a prospective interventional study.

Methods: Renal phosphate leak was identified based on the occurrence of idiopathic hypophosphatemia [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) reference units (RU)/ml, respectively]. Stone formers with renal phosphate leak showed lower FGF23, compared with patients with oncogenic osteomalacia and X-linked hypophosphatemic 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 (r = –0.784, P = 0.009) and the rate of tubular phosphate reabsorption (r = –0.791, 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.

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