Study of the Impact of Phosphate Supplementation on FGF23 Concentrations in Patients With Hypophosphatemia

Fibroblast growth factor 23 (FGF23) is the principal hormone regulating serum phosphate homeostasis. Secreted by osteocytes, it promotes renal phosphate excretion and suppresses the synthesis of 1,25-dihydroxyvitamin D. Measurement of FGF23 has become a key tool in the evaluation of hypophosphatemia, allowing distinction between FGF23-dependent forms (such as X-linked hypophosphatemic rickets, tumor-induced osteomalacia, and intravenous iron-induced hypophosphatemia) and FGF23-independent forms (including renal, gastrointestinal, nutritional, or drug-related causes). In healthy adults, several studies have demonstrated that FGF23 levels vary according to phosphate intake, decreasing during dietary restriction and increasing following phosphate loading. In hypophosphatemic conditions, however, available data are limited to X-linked hypophosphatemic rickets, where prolonged supplementation with phosphate and calcitriol leads to increased FGF23 levels, consistent with the underlying pathophysiology. Based on these observations, it is currently recommended, as a precaution, to measure FGF23 at least 15 days after discontinuation of phosphate supplementation in order to avoid transient elevations that may confound interpretation. In practice, however, this recommendation is difficult to implement, as most patients are already receiving phosphate supplementation at the time of evaluation. To date, no study has specifically assessed the effect of phosphate supplementation in patients with FGF23-independent hypophosphatemia, a condition characterized by appropriately low FGF23 levels. It therefore remains unclear whether supplementation could induce a transient rise in circulating FGF23, potentially leading to misclassification as FGF23-dependent hypophosphatemia (FGF23 \> 95 ng/L). This uncertainty provides a strong rationale for conducting the present study.

Inclusion Criteria: * Patients hospitalized in adult intensive care, oncology, or rheumatology * Hypophosphatemia \< 0.8 mmol/L * Clinical indication for phosphate supplementation Exclusion Criteria: * Chronic kidney disease, stage ≥ 3 (eGFR \< 60 mL/min/1.73 m²) * Treatment with Ferinject® within the past year * Sepsis * Current treatment with active vitamin D * Pregnancy or breastfeeding * Inability to perform blood draws due to insufficient venous access * Weight \< 35 kg (for intensive care patients only) * Hypercalcemia \> 2.6 mmol/L