True hypophosphatemia can be induced by decreased net intestinal absorption, increased urinary phosphate excretion, or acute movement of extracellular phosphate into the cells. Spurious hypophosphatemia can be caused by interference of paraproteins with the phosphate assay . (See "Causes of hypophosphatemia".)
The normal renal response to phosphate depletion is to increase phosphate reabsorption, leading to the virtual abolition of phosphate excretion in the urine. Most of the filtered phosphate is reabsorbed in the proximal tubule via the sodium-phosphate cotransporter in the luminal membrane [2,3]. This transporter uses the favorable inward concentration gradient for sodium (the cell sodium concentration is less than 25 meq/L, well below the 145 meq/L concentration in the tubular lumen) to drive the active reabsorption of phosphate from the tubular lumen into the cell. Phosphate depletion leads to increased gene expression and synthesis of new transporters, thereby enhancing the uptake of filtered phosphate into the cell .
The cause of hypophosphatemia is often evident from the history (table 1) (see "Causes of hypophosphatemia"). If, however, the diagnosis is not apparent, then measurement of urinary phosphate excretion should be helpful. Phosphate excretion can be measured either from a 24-hour urine collection or by calculation of the fractional excretion of filtered phosphate (FEPO4) from a random urine specimen.
In patients with hypophosphatemia:
●A 24-hour urine phosphate excretion less than 100 mg or a FEPO4 less than 5 percent indicates appropriate low renal phosphate excretion, suggesting that the hypophosphatemia is caused by internal redistribution (eg, refeeding syndrome, acute respiratory alkalosis) or decreased intestinal absorption (eg, chronic antacid therapy, steatorrhea). (See "Causes of hypophosphatemia", section on 'Internal redistribution' and "Causes of hypophosphatemia", section on 'Decreased intestinal absorption'.)