Cation effects on phosphate homeostasis in hypophosphatemic subjects.

Abstract

X-linked hypophosphatemia and sporadic hypophosphatemic osteomalacia are disorders characterized by inappropriately high renal clearance of phosphate (Pi). Although the results of some studies have suggested an additional defect in intestinal Pi absorption1,2 excessive urinary Pi excretion is generally considered to be the major determinant of the hypophosphatemia. Treatment with oral Pi salts alone or in combination with vitamin D has resulted in increased serum Pi levels and improvement in bone disease3. Oral Pi supplements have most often been administered in the form of the neutral sodium (Na) salts or as a combination of neutral Na and potassium (K) salts. Frick4 has demonstrated that expansion of extracellular fluid volume by the infusion of isotonic saline results in increased Pi excretion in the rat. Similar effects of saline infusion on Pi excretion have been observed in dogs5,6 and normal human subjects7. Recently Tenenhouse et al8 in studies of the X-linked hypophosphatemic mouse, have suggested the presence of a selective Pi transport defect in the Na dependent transport system of the kidney brush border membrane. In order to evaluate the effects of high Na intake in individuals receiving oral Pi supplements, we have compared the effects of neutral Na and K salts of Pi on levels of serum Pi, renal Pi clearance, immunoreactive parathyroid hormone (PTH) and urinary cAMP clearance in three adults with hypophosphatemic osteomalacia. In all three subjects, serum Pi levels were higher while receiving the neutral K salt of Pi than while receiving equivalent quantities of the neutral Na salt. In one subject with X-linked hypophosphatemia, a high Na diet reversed the beneficial effects of the K salt on serum Pi levels. These studies suggest that Pi excretion is markedly affected by Na intake in individuals with hypohosphatemic osteomalacia.