Evidence for an intrinsic renal tubular defect in mice with genetic hypophosphatemic rickets

To investigate the role of parathyroid hormone (PTH) and(or) an intrinsic renal tubular reabsorptive defect for phosphate in mice with hereditary hypophosphatemic rickets, the authors performed clearance and micropuncture studies in hypophosphatemic mutants and nonaffected littermate controls. Increased fractional excretion of phosphate in mutants (47.2±4 vs. 30.8±2% in controls) was associated with reduced fractional and absolute reabsorption in the proximal convoluted tubule and more distal sites. Acute thyroparathyroidectomy (TPTX) increased phosphate reabsorption in both mutants and controls with a fall in fractional phosphate excretion to ≃7.5% in both groups indicating that PTH modified the degree of phosphaturia in the intact mutants. Absolute reabsorption in the proximal tubule and beyond remained reduced in the mutants, however, possibly because of the reduced filtered load. Serum PTH levels were the same in intact mutants and normals as was renal cortical adenylate cyclase activity both before and after PTH stimulation. Hereditary hypophosphatemia in the mouse is associated with a renal tubular defect in phosphate reabsorption, which is independent of PTH and therefore represents a specific intrinsic abnormality of phosphate transport.