Effect of diphosphonate treatment on phosphate transport by renal brush border vesicles

Treatment with disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) given in doses of 10 mg P/kg s.c. for 7 days inhibits bone mineral retention and decreases the tubular capacity to reabsorb inorganic phosphate (Pi) in thyroparathyroidectomized (TPTX) rats. In the present work we show that pretreatment with EHDP depressed Na+-dependent Pi uptake by brush border membrane vesicles (BBMV) isolated from renal cortex of TPTX rats. The effect of EHDP was observed after feeding both high (1.2%) and low (0.2%) phosphorus diets. The EHDP-induced changes observed in vitro at the brush border level parallel the variations in the overall tubular Pi transport capacity as assessed by clearance techniques in conscious rats. Na+-dependent glucose uptake by BBMV, as well as alkaline phosphatase activity in cortical homogenates and in the BBMV were not affected by EHDP treatment. Accordingly, EHDP, given in doses that block bone mineral retention, appears to specifically affect the Na+-dependent transport of Pi across the luminal membrane of proximal tubules of renal cortex.