Effects of Phosphate Loading and Depletion on the Renal Excretion and Reabsorption of Inorganic Phosphate

Abstract

A number of studies have indicated that parathyroid extract increases the renal excretion of phosphate (1)(2)(3)(4)(5)(6). This effect appears to result from a depression of the renal reabsorption of phosphate (6). Endogenous secretory activity of the parathyroid glands has been related to the extracellular concentration and/or the dietary intake of calcium and phosphate. Although dietary variations of these ions did not correlate consistently with TmP 8 in our initial investigations (7), other workers have demonstrated an influence of diet on phosphate reabsorption. A high phosphate diet led to a diminished P reabsorption in normal but not in parathyroidectomized rats (8). Studies in dogs (9) and in normal human subjects (8, 10) also indicated that the level of P intake influenced P reabsorption, but whether this effect was mediated by the parathyroid glands is not clear. In order to examine more rigorously the effects of a high P intake, buffered sodium phosphate solutions were administered intravenously daily for four to eight days to the normal and hypoparathyroid subjects previously described (7). Another phase of this study involved an inquiry into the mechanism by which aluminum gels produce a marked reduction in urinary P.Variations in plasma levels of Ca and P often occur together. An attempt was made to separate the effects of elevation of plasma P from the frequently seen simultaneous reduction in plasma Ca.Our data indicate that repeated daily intravenous administration of large quantities of phos- phate results in a reduction in renal P reabsorption. This effect does not appear to depend upon an associated reduction in plasma Ca. Whether this effect is mediated via the parathyroids cannot be conclusively stated. The results indicate that aluminum gels produce their effect primarily, and perhaps solely, by effecting a reduction in plasma P. METHODSThese studies were conducted on the same patients previously described, and the measurements of TmP were carried out by the method detailed in an earlier paper (7). In studies of the effects of intravenously administered phosphate, a buffered sodium phosphate solution, pH 7.4, was infused over a 4 to 6-hour period on four consecutive days. Five subjects received 75 mM of P each day; two subjects, C. H. and D. F., received 90 and 150 mM P per day, respectively. Two of the normal subjects, C. H. and E. P., received eight daily P infusions, and on the last four days they received, in addition, infusions of Ca. The Ca was administered as calcium gluconate, 15 mg. Ca per kg. of body weight in 1,000 ml. of 5 per cent glucose in water, over a fourhour period starting several hours after the completion of the phosphate infusion. Infusions of di-sodium ethylenediamine tetraacetic acid (EDTA) were given to the four normal subjects who received intravenous phosphate. Four gm. of EDTA was administered in 1,000 ml. of 5 per cent glucose in water over a 4 to 6-hour period daily for four consecutive days. TmP was measured prior to, and on the day following completion of t...

Inorganic phosphate homeostasis. Renal adaptation to the dietary intake in intact and thyroparathyroidectomized rats.

“…In these studies it has mostly been shown that dietary Pi (9). Furthermore, most studies aimed at assessing an influence of dietary Pi on the renal tubule have been carried out either at endogenous [Pi]pi or at a level where maximum tubular reabsorption of Pi (TmPt) was supposed to take place (4,(10)(11)(12)(13). Therefore such data cannot be interpreted as evidence for a modification of the tubular capacity to transport Pi.…”

Observations on Phosphate Transport in Experimental Renal Disease*

“…This fraction is decreased when the dietary phosphorus is low and increased when it is high. Homeostasis is thus maintained with only slight fluctuations of the plasma phosphate concentration (2)(3)(4)(5)(6).…”

Some Effects of Intravenously Administered Calcium on Inorganic Phosphate Metabolism

“…The apparent relationship of serum or dietary Ca to parathyroid secretion does not, of course, preclude the possibility that other factors influence both parathyroid function and phosphate transport by the renal tubule. Indeed, a profound depression of TmP was demonstrated following the intravenous administration of large quantities of P, and this phenomenon was not reversed by the repeated intravenous administration of Ca (9). The mechanism of the increase in plasma P which follows a rise in serum Ca has not been demonstrated in these studies.…”