Effect of 1,25-Dihydroxyvitamin D3 on the Renal Handling of Pi in Thyroparathyroidectomized Rats

Abstract

The kidney adapts its tubular capacity to transport inorganic phosphate (P_i) according to the dietary supply of P_i in both intact and thyropara-thyroidectomized (TPTX) rats. However, in TPTX rats the capability of the renal tubule to adapt to a high P_i diet is diminished. In TPTX rats the production of the active vitamin D₃ metabolite, 1,25-dihydroxyvitamin D₃ [1,25-(OH)₂D₃], is also reduced. 1,25-(OH)₂D₃ has been shown to have a marked effect on P_i metabolism. Therefore the question arises whether the deficient production of 1,25-(OH)₂D₃ contributes to the alteration of the tubular transport of P_i observed in chronically TPTX rats. In the present investigation, vitamin D-replete rats were sham operated (SHAM) or thyroparathyroidectomized and then pair fed diets containing either 0.2 or 1.2 g/100 g P for 7 days. During this period, groups of SHAM and TPTX rats received i.p. 2 × 13 pmol/day of 1,25-(OH)₂D₃, a dose which was shown to just normalize the decreased intestinal absorption of Ca and P_i in TPTX rats. The capacity of tubular P_i transport was then assessed by measuring the fractional excretion of P_i (FEP_i) at increasing plasma P_i concentration ([P_i]_Pl) obtained by acute infusion of P_i. The results show that in SHAM rats fed either P diet, 1,25-(OH)₂D₃ has no effect on the renal handling of P_i. In TPTX rats fed 1.2 g/100 g P diet, 1,25-(OH)₂D₃ increases FEP_i over a wide range of [P_i]_Pl. In TPTX rats fed a 0.2 g/100 g P diet, 1,25-(OH)₂D₃ does not alter FEP_i up to a [P_i]_Pl of 3.0-3.5 mM, but does increase it at higher [P_i]_Pl. In fact, on both diets TPTX rats supplemented with 1,25-(OH)₂D₃ appear to have the same renal handling of P_i as SHAM counterparts. The effect of 1,25-(OH)₂D₃ was not associated with a change in urine pH or in urinary excretion of cyclic AMP and was maintained under marked extracellular volume expansion. It was associated with a rise in plasma calcium in the TPTX rats fed the high, but not the low, P diet. In TPTX rats fed 1.2 g/100 g P diet, 25-hydroxyvitamin D₃ in doses of 2 × 130 or 2 × 1,300 pmol/day i.p. did not increase FEP_i. In conclusion, 1,25-(OH)₂D₃ administered in physiological amounts to TPTX rats restores to normal the capability of the renal tubule to excrete P_i and to adapt to large variation in dietary P_i. The results suggest that 1,25-(OH)₂D₃ plays an important role in the regulation of the renal handling of P_i and that the chronic change in the tubular capacity to transport P_i after TPTX may be due to the decreased formation of 1,25-(OH)₂D₃.