Parathyroid hormone and renal handling of Pi: effect of dietary Pi and diphosphonates

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Abstract
The kidney adapts its tubular handling of Pi in response to variations in the dietary Pi supply. The question arises as to whether the demand for Pi could also influence the tubular Pi transport capacity. The renal handling of Pi in thyroparathyroidectomized (TPTX) rats was studied during chronic treatment with ethane-1-hydroxy-1,1-diphosphonate (EHDP) at a dose which inhibits bone mineral retention and, therefore, the demand for Pi in these growing animals. The effect of EHDP was studied under both low (0.2 g/100 g) and high (1.2 g/100 g) P diets and compared with another diphosphonate (dichloromethane diphosphonate, Cl2MDP) at a dose which markedly reduces bone turnover but does not inhibit bone mineral retention. EHDP, but not Cl2 MDP, decreased the capacity of the tubule to reabsorb Pi. Although EHDP inhibits renal production of 1,25-dihydroxyvitamin D3, treatment with this metabolite did not reverse the effect of EHDP on tubular resorptive capacity for Pi. The tubular response to parathyroid hormone (PTH) was also investigated in TPTX rats pair-fed a 0.2 or a 1.2 g/100 g P diet with and without EHDP treatment. In rats fed the low Pi diet the phosphaturic response to PTH was blunted over a wide range of plasma and filtered load of Pi. EHDP produced a phosphaturic response to PTH similar to that obtained in control rats fed a high Pi diet. With a high Pi diet, EHDP enhanced further the phosphate excretion in response to PTH without augmenting the urinary cAMP response. Cl2MDP treatment did not enhance the phosphaturic response to PTH. The EHDP effect on the renal handling of Pi might represent a homeostatic response determined by the reduced capacity of bone to incorporate Pi.