1184 PERSISTANCE OF THE DEFECT IN RENAL BRUSH-BORDER MEMBRANE PHOSPHATE TRANSPORT IN 1α,25-(OH)2 VITAMIN D3 (l,25-(OH)2D3)-TREATED X-LINKED HYPOPHOSPHATEMIA

Abstract

We studied the effect of 1,25(OH)2D3 on phosphate (Pi) homeostasis in the Hyp mouse, a homologue of X-linked hypophosphatemia in man. 1,25(OH)2D3 (83 pg/g·day, infused subcut. × 10 days) produced significant hypercalcemia in normal mice (11.34±0.07 vs 10.14±0.15 mg/dl, p<0.001) and a rise in fractional excretion index of Ca (FEICa) (0.037±0.007 vs 0.005±0.001, p <0.001), without significant alteration of serum Pi (8.94±0.46 vs 8.36±0.23 mg/dl, NS), FEIpi (0.21±0.02 vs 0.19±0.03, NS) or Na+-stimulated Pi transport by purified renal brush-border membrane vesicles (BBMV) (844±32 vs 764±41 pmoles/mg protein·15s, NS). At this dose, 1,25(OH)2D3 had no observable effect in Hyp littermates. At 415 pg/g·day, Hyp mice experienced an increase in serum Ca (11.25 ±0.44 vs 9.64±0.06 mg/dl, p <0.001), FEICa (0.013±0.003 vs 0.005±0.001, p <0.005) and serum Pi (7.70±0.29 vs 4.35±0.15 mg/dl, p <0.001) but no change in FEIpi (0.40±0.05 vs 0.45±0.05, NS) and no enhancement of Na+-stimulated Pi transport by renal BBMV (385±23 vs 359±50 pmoles/mg protein·15s, NS). We conclude that 1,25(OH)2D3 does not correct the renal BBM transport defect in Hyp mice, at the supraphysiologic dose that improves Pi homeostasis. On the other hand, 1,25(OH)2D3 enhances (p <0.02) intestinal absorption of Pi in the Hyp mouse, thus explaining its effect on Pi homeostasis in the mutant phenotype of mouse and man.