Matrix extracellular phosphoglycoprotein causes phosphaturia in rats by inhibiting tubular phosphate reabsorption

BACKGROUND: Matrix extracellular phosphoglycoprotein (MEPE), first isolated from tumour-derived tissue from a patient with oncogenic hypophosphataemia, is a putative phosphatonin that has received much less attention than fibroblast growth factor-23. To date, its effect on renal tubular phosphate reabsorption remains undefined. METHODS: A renal clearance study was performed in anaesthetized rats infused intravenously with a range of doses of MEPE. RESULTS: MEPE had no effect on glomerular filtration rate (inulin clearance) but caused rapid, dose-dependent increases in absolute and fractional phosphate excretion, wholly attributable to reduced phosphate reabsorption. At a maximal dose, MEPE increased fractional phosphate excretion more than 2-fold, whereas no change was observed in time controls. CONCLUSION: The results lend support to the hypothesis that MEPE contributes to the phosphaturia of oncogenic hypophosphataemia and of hypophosphataemic rickets.