phosphatewasting

Phosphate wasting refers to renal loss of phosphate due to impaired proximal tubule reabsorption, resulting in hypophosphatemia. The majority of phosphate reabsorption occurs in the proximal tubule through sodium-phosphate cotransporters NaPi-IIa and NaPi-IIc. Hormonal regulators such as fibroblast growth factor 23 (FGF23), parathyroid hormone, and vitamin D influence this reabsorption; when reabsorption is reduced, phosphate is excreted in urine.

Causes of phosphate wasting include hereditary hypophosphatemic disorders, such as X-linked hypophosphatemia and other familial forms, as well as acquired conditions like Fanconi syndrome, which involves generalized proximal tubule dysfunction. Acquired causes also include certain drugs (for example, ifosfamide, cisplatin, tenofovir), heavy metal exposure, and other systemic diseases that impair tubular function. Nutritional phosphate deficiency is a less common cause.

Clinical features depend on age and the severity of phosphate loss. In children, chronic phosphate wasting can cause rickets with bone deformities, short stature, and dental problems. In adults, it may present as osteomalacia with bone pain, fractures, and muscle weakness. Some individuals may be asymptomatic and identified via laboratory testing.

Diagnosis hinges on laboratory findings showing low serum phosphate with inappropriately high urinary phosphate excretion (a reduced tubular reabsorption of phosphate, or low TmP/GFR). Calcium levels are typically normal; alkaline phosphatase may be elevated in bone disease. Further evaluation may include assessments for Fanconi syndrome and measurement of FGF23 to guide management.

Treatment focuses on addressing the underlying cause. Therapeutic options include phosphate supplementation with active vitamin D analogs, and in some hereditary hypophosphatemias, targeted therapy with an anti-FGF23 antibody (burosumab). Regular monitoring is essential to avoid complications such as nephrocalcinosis or secondary hyperparathyroidism.