Has vitamin D a direct renal effect on the tubular reabsorption of phosphate? A study in parathyroidectomized (PTX) and non-PTX man

Abstract

The effect of 1-alpha-hydroxycholecalciferol (1alpha-OH-D3) on the renal handling of phosphate and the immunoreactive parathyroid hormone in serum (i-PTH) has been studied in 10 patients with a wide range of glomerular filtration rate (GFR), maximal tubular reabsorption of phosphate (TmP) and i-PTH. The patients were treated with 2 microgram 1alpha-OH-D3 per day for approximately 80 days. Before and after this period of treatment, the TmP, i-PTH, 51Cr EDTA clearance, extracellular volume, standard bicarbonate, and serum calcium were measured in each patient. The TmP/GFR ratio was used as an index of the renal handling of phosphate. The index increased significantly (mean 26.5%, p less than 0.01) during the treatment, while i-PTH decreased significantly (mean 37.0%, p less than 0.01). A significant inverse correlation was demonstrated between the TmP/GFR index and i-PTH both before (r = -0.87; p less than 0.001) and after (r = -0.79; p less than 0.01) the administration of 1alpha-OH-D3, while none of the other factors investigated were correlated to the index. This may suggest that the stimulating effect of biologically active vitamin D on the tubular reabsorption of phosphate is mediated via the parallel suppression of PTH, but does not exclude that biologically active vitamin D exerts a direct effect on the human renal tubule. Therefore, the effect of 1alpha-OH-D3 was studied in 5 totally parathyroidectomized patients, in whom concomitant suppression of PTH would not occur. Estimation of TmP/GFR was performed 1) when the patients were vitamin D depleted and hypocalcemic, and 2) after 14-27 days of treatment with 1alpha-OH-D3 to obtain stable normocalcemia. In patients with absent parathyroid function, no increasing effect of 1alpha-OH-D3 on TmP/GFR could be demonstrated. It is therefore concluded 1) that 1alpha-OH-D3 exhibits no antiphosphaturic effect in the absence of PTH and 2) that the previously demonstrated antiphosphaturic effect of 1alpha-OH-D3 in man is mediated via a concomitant suppression of PTH.