We describe a case of a 26-year-old man with refractory hypophosphatemia following an iron infusion necessitating two hospital admissions over 8 weeks who was successfully treated with one dose of burosumab.
The patient presented with a critically low serum phosphate <0.3mmol/L two weeks after receiving an infusion of ferric polymaltose. He previously developed hypophosphatemia following a ferric carboxymaltose infusion 6 months earlier which was treated with oral phosphate, calcium carbonate and calcitriol over 3 months. Medical history included low bone density and common variable immunodeficiency with immune dysregulation including severe Crohn’s disease, eczema and asthma.
Investigations on admission demonstrated severe hypophosphatemia (<0.3mmol/L), mild hypocalcaemia (1.93mmol/L), elevated parathyroid hormone (13.9pmol/L) with replete 25-OH-vitamin D (136nmol/L) and normal renal function (eGFR>90ml/min). His TmP/GFR was 0.28mmol/L suggestive of renal phosphate wasting. His FGF-23 level was significantly elevated 317ng/L (RI 23.3-95.4) consistent with reduced degradation of FGF-23 secondary to iron infusion.
Despite maximal oral replacement with phosphorous 1.5g three times daily, calcitriol 0.75mcg twice daily and magnesium 1g twice daily (all dosed separately) and intravenous phosphate infusions second daily as an outpatient, he had persistent hypophosphatemia, requiring hospital readmission. This impacted the patient's mental health significantly and led to the deferment of tertiary studies. After 37 days of refractory hypophosphataemia, he was given burosumab, a monoclonal antibody against FGF-23. Five days following burosumab 20mg (0.3mg/kg), the patient’s phosphate normalised to 1.17mmol/L from 0.47mmol/L without any oral phosphate or calcitriol. His spot renal phosphate excretion decreased from 55mmol/L to <1.6mmol/L with a TmP/GFR of 1.72mmol/L. The FGF-23 level remained elevated at 181ng/L and 654ng/L five days and one month after the injection respectively. At four months follow-up, he had normal phosphate without need for any further oral supplementation.
Burosumab, a FGF-23 inhibitor, is an effective treatment for refractory FGF-23 mediated hypophosphatemia following iron infusion.