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

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Abstract

The kidney adapts its tubular capacity to transport inorganic phosphate (Pi) according to the dietary supply of Pi in both intact and thyropara-thyroidectomized (TPTX) rats. However, in TPTX rats the capability of the renal tubule to adapt to a high Pi 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 Pi metabolism. Therefore the question arises whether the deficient production of 1,25-(OH)2D3 contributes to the alteration of the tubular transport of Pi 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 Pi in TPTX rats. The capacity of tubular Pi transport was then assessed by measuring the fractional excretion of Pi (FEPi) at increasing plasma Pi concentration ([Pi]Pl) obtained by acute infusion of Pi. The results show that in SHAM rats fed either P diet, 1,25-(OH)2D3 has no effect on the renal handling of Pi. In TPTX rats fed 1.2 g/100 g P diet, 1,25-(OH)2D3 increases FEPi over a wide range of [Pi]Pl. In TPTX rats fed a 0.2 g/100 g P diet, 1,25-(OH)2D3 does not alter FEPi up to a [Pi]Pl of 3.0-3.5 mM, but does increase it at higher [Pi]Pl. In fact, on both diets TPTX rats supplemented with 1,25-(OH)2D3 appear to have the same renal handling of Pi 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 FEPi.

Authors

J-P. Bonjour, C. Preston, H. Fleisch