Interaction of Parathyroid Hormone and Vitamin D on the Renal Excretion of Phosphate*

172

The kidney provides a sensitive mechanism which aids in the maintenance of phosphorus equilibrium despite varying intakes and alterations in metabolic demand. Under normal conditions a large proportion of the phosphorus which is filtered at the glomerulus is reabsorbed by the tubules which thereby effect regulation of the urinary phosphorus (1). Few studies have been performed on patients or animals to determine how phosphorus homeostasis is maintained as renal function is progressively decreased (2, 3). It is well known that the concentration of serum inorganic phosphorus increases and of calcium decreases as renal failure becomes more pronounced (446), and that anatomical changes occur in the parathyroid glands which suggest hyperfunction of these organs (7). Since the parenteral administration of parathyroid hormone produces an increased phosphaturia, a decrease in the serum phosphorus, and an increase in the serum calcium, it is possible that the parathyroid hyperplasia represents a physiologic attempt to reverse these specific effects of renal failure (8). It seemed appropriate, therefore, to investigate the relationship of phosphate clearance to the general level of renal function and to test the response to exogenous parathyroid hormone at all gradations of renal impairment to determine whether a further response was possible or whether maximal effectiveness had been achieved by endogenous hormone activity. MATERIALS AND METHODSA series of twenty males between the ages of 25 and 60 years was selected. Their glomerular filtration rates as measured by inulin clearance varied from 142 to 1.5 1 This work was supported in part by a grant-in-aid from the U. S. Public Health Service, Heart Institute, Grant No. H-1004 (C); and the Riker Laboratories, Inc., Los Angeles, California. ml. per minute, and covered the entire range of renal function from normal to advanced uremia. Those with reduced renal function had various diseases, chiefly chronic glomerulonephritis and chronic pyelonephritis. The patients with normal kidneys had been maintained on the regular hospital diet which provided 90 to 100 grams of protein and about 1.5 grams of phosphorus per day. Most of the patients with reduced renal function had ingested a diet in which the protein was restricted to about 40 grams and, the phosphorus intake to approximately 0.75 grams per day.Clearances were performed during the postabsorptive state and the glomerular filtration rate was measured by the use of inulin in all but four experiments in which the endogenous creatinine clearance was substituted. Three control periods of approximately 20 minutes each were obtained 30 minutes after the injection of the priming dose of inulin. Blood was drawn for the determination of serum inulin and phosphorus at the midpoint of each clearance period. During the fourth 20-minute period 500 units of parathyroid hormone 2 (Lilly) was given by slow intravenous injection. Three additional 20-minute clearance periods were obtained following the administration of the hormone. A satis...

supporting

confidence: 76%

Phosphorus Excretion in Renal Failure1

Goldman¹,

Bassett²

1954

172

“…Those reports which are available regarding alterations in renal phosphate (and calcium) reabsorption secondary to an action of the vitamin are difficult to interpret for one or more of the following reasons. First, in intact animals, there is the distinct possibility that the changes noted could have resulted from variations in circulating levels of parathyroid hormone (PTH)' and/or thyrocalcitonin (7,11,12). Secondly, the absolute level of the serum calcium concentration and the degree of vitamin D depletion appear to be important in and of themselves in establishing the level of excretion of phosphate by the kidney (13)(14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Evidence for a Direct Action of Cholecalciferol and 25-Hydroxycholecalciferol on the Renal Transport of Phosphate, Sodium, and Calcium

Puschett¹,

Moranz²,

Kurnick³

1972

197

“…

…”

mentioning

confidence: 99%

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

Thompson¹,

Hiatt²

1957

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...