The Renal Excretion of Inorganic Phosphate in Relation to the Action of Vitamin D and Parathyroid Hormone 1

Abstract

The mode of action of vitamin D in the prevention and cure of rickets is still not understood. In 1921, Howland and Kramer (1) pointed out that the concentration of phosphorus in the serum was usually reduced in human rickets, at times to very low levels, although the concentration of calcium might be within normal limits. This has been confirmed repeatedly and it has been found that the administration of vitamin D results in a prompt rise in the concentration of phosphorus, even to abnormally high levels with excessive dosage. The mechanism through which vitamin D influences the concentration of phosphorus in the body fluids has not been satisfactorily explained. In balance experiments in man (2, 3) and experimental animals (4) it has been shown that during states of vitamin D deficiency absorption of calcium and phosphate from the intestinal tract is reduced and that the administration of vitamin D increases the absorption of these ions. In the rat, the studies of Nicolaysen (5) Careful examination of the data from metabolic studies in the rachitic infant leads to the conclusion that deficient absorption of phosphate from the intestinal tract cannot wholly explain the diminished concentration of phosphate in the plasma. In infants developing rickets on a cow's milk diet, i.e., a diet high in both calcium and phosphorus, the amount of phosphate absorbed from the intestinal tract would be sufficient for the needs of the infant were the phosphate retained rather than excreted in the urine.The excretion of phosphate in the urine must play an important r6le in the regulation of the concentration of phosphate in the body fluids. How is the renal excretion of phosphate controlled and does vitamin D influence the concentration of phosphate in the blood plasma through an effect on the excretion of this ion by the kidneys? The present experiments were conducted to answer these questions. The Renal Excretion of PhosphateWalker (6) and Walker and Hudson (7) have shown that the phosphate of the plasma is filtrable through the glomerular membranes of the amphibian. These workers have also found that under certain conditions active reabsorption of phosphate takes place in the proximal tubules so that the urine in the distal tubules and bladder may be almost phosphate-free. There was no evidence that phosphate was secreted into the lumen of the tubules.In the dog, Pitts (8) has shown that the clearance of phosphate increases as the concentration of phosphate in the plasma increases and approaches the xylose clearance at very high levels of plasma phosphate. At normal levels of phosphate in the blood plasma the urine may be almost phosphate-free and the excretion of phosphate in the urine is only a small fraction of that filtered through the glomeruli. In the mammalian kidney, therefore, reabsorption of phosphate must also take place as the glomerular filtrate passes through the renal tubules.In order to study this tubular reabsorption of phosphate quantitatively, simultaneous determinations of the creatinine and phosphate c...

The Parathyroid Glands and Phosphorus Homeostasis 12

“…For example, it has been suggested that parathyroid hormone may alter certain physical characteristics of the phosphates in body fluids so as to render a greater fraction of the total blood phosphorus filterable at the glomerulus (12). Certain published data, however, fail to support this thesis (27,34,35) and in our own studies we have been unable to detect any significant change in the various moieties of total blood phosphorus either in sivo or in vitro as a consequence of parathyroid extract administration. Harrison and Harrison (27) and Pitts and associates (36,37) have suggested that a renal tubular maximal capacity for phosphorus reabsorption (TmP) exists.…”

“…was calculated as the product of glomerular filtration rate and plasma or serum inorganic phosphorus concentration (27,28). Phosphorus reabsorbed by the renal tubules (T.R.P.)…”

“…was found as the difference between glomerular filtrate and urinary phosphorus (U.P.) (27). In certain sections of the manuscript the ratio, T.R.P./ G.F.P., is used to indicate the portion of phosphorus filtered at the glomerulus which is reabsorbed by the renal tubules.…”

Handling of phosphate by the human kidney at high plasma concentrations

“…Since this subject usually showed a high Tm, it is not surprising that his saturation threshold was also high. (Roberts & Pitts, 1953) and vitamin D (Harrison & Harrison, 1941), are said to depress phosphate reabsorption, but there is no evidence whether these or other factors are responsible for the variations here reported. Hogben & Bollman (1951) found in the dog that phosphate Tm declined progressively to 25-50 % of its initial value during a series of clearance periods extending over 3-4 hr, and that this decline was usually prevented by adding potassium to the infusate.…”

Tubular Reabsorption of Phosphate in the Dog 12

“…The method of calculation is that of Harrison and Harrison (1). Rate of glomerular filtration for each period is calculated by multiplying together creatinine clearance and mean concentration of phosphate in serum.…”