Plasma intact fibroblast growth factor 23 level is a useful tool for diagnostic approach of renal hypophosphatemia

Background Primary hypophosphatemic syndromes are a heterogeneous group of rare diseases. In recent years, fibroblast growth factor 23 (FGF23) has been postulated as a useful tool for differential diagnosis of hypophosphatemic rickets characterized by impaired renal phosphate reabsorption. This study aimed to investigate the utility of FGF23 to discriminate between X-linked hypophosphatemic rickets (XLH), an FGF23-driven disease, from other causes of renal phosphate wasting such as Fanconi syndrome (FS), a generalized dysfunction of the proximal tubule unrelated to FGF23. Methods Circulating levels of intact FGF23 (iFGF23) were measured in nine children with XLH receiving conventional therapy (six girls, mean +/- SD age 10.8 +/- 6.7 years) and nine children with secondary FS (four girls, mean +/- SD age 9.9 +/- 5.2 years), using an automated chemiluminescent immunoassay. Phosphate, calcium, creatinine, estimated glomerular filtration rate (eGFR), intact parathormone (iPTH), and urinary parameters were evaluated simultaneously. Maximum renal tubular threshold for phosphate reabsorption (TmP/GFR) was also estimated. Results Plasma iFGF23 concentrations in patients with XLH were significantly higher than those in the SF group: 146.2 +/- 69.2 ng/L vs. 29.5 +/- 15.0 ng/L (p < 0.001). Remarkably, we did not observe an overlap between XLH and FS patients. Significant hypophosphatemia (2.55 +/- 0.50 mg/dL) and secondary hyperparathyroidism (iPTH 109.4 +/- 58.1 ng/mL) were present in XLH patients, while FS patients showed modest hypophosphatemia (3.97 +/- 0.68 mg/dL), higher TmP/GFR compared with XLH, lower eGFR and hypercalciuria. Conclusions This study supports the value of measuring FGF23 levels as a useful tool to exclude XLH in patients with increased phosphate wasting of kidney origin.

Automated summary

This study found that measuring FGF23 levels is a useful tool to exclude XLH in patients with increased phosphate wasting of kidney origin. It can effectively discriminate between XLH and FS.