Hypophosphataemia can be a challenging entity to treat, especially when there are multifactorial aetiologies. Proximal renal tubular acidosis (RTA) occurs due to the inability of bicarbonate reabsorption in the proximal tubules. Aetiologies include light chain nephropathy, multiple myeloma, Fanconi syndrome, and exposure to drugs including tacrolimus and aminoglycosides.1 Osteomalacia is often associated with proximal RTA due to renal phosphate wasting. Other important causes of hypophosphataemia include iron transfusions (mediated by FGF23 usually) and denosumab.2, 3
We present a case of a 36-year-old female who presented to ICU for electrolyte management, in the context of an acute ileus and reduced bone density on denosumab (previous renal transplant and long-term TPN). On admission there was severe hypophosphataemia (<0.3mmol/L, NR 0.75-1.5) and hypokalaemia (2.9mmol/L, NR 3.5-5.2). Renal function was in range with a creatinine of 50umol/L (NR 45-90), eGFR >90mL/min/1.73m2. There was a concomitant non-anion gap metabolic acidosis with type 2 proximal RTA, and her FGF23 level was 30ng/L (NR 23.2-95.4). In the preceding month, the patient had received an intravenous infusion of ferric carboxymaltose 500mg, and a scheduled dose of denosumab 60mg. Other contributing factors to the severe hypophosphataemia included malnutrition, and vitamin D deficiency (level 35nmol/L, NR 50-140). Initial management consisted of high-dose IV electrolyte replacement. Oral electrolyte therapy was instituted once the ileus had resolved, as well as high-dose vitamin D replacement.
This case demonstrated severe renal phosphate wasting, reflecting some degree of dysfunction in the FG23-phosphate pathway. There was a balance of processes including a decrease in FGF23 (due to RTA, malabsorption), and an increase (iron transfusion, hyperparathyroidism, and denosumab). These situations require a combination of oral and intravenous replacement, particularly whilst waiting for the effects of denosumab and iron transfusions to wane, as well as addressing underlying pathologies driving the dysfunction.