Renal Tubular Handling Of Calcium Research Articles

Follow up of workers previously exposed to silver solder containing cadmium.

OBJECTIVES: To study longitudinal biological monitoring data on urinary and blood cadmium collected in a small cohort of nine workers who had been brazing for several years with solders containing...

Renal tubular reabsorption of calcium and sodium in primary hyperparathyroidism

Nine patients with primary hyperparathyroidism were studied to investigate the renal tubular reabsorption of calcium and sodium. Fasting serum and urine samples were analysed, and the glomerular filtration rate and the renal plasma clearance of lithium were determined simultaneously. Comparison was made with 9 age- and sex-matched normocalcemic controls. In the proximal tubule, there was a significantly higher absolute reabsorption of calcium in patients than in controls, whereas the fractional reabsorption rate of calcium did not differ between the two groups. In the distal tubule, the absolute calcium reabsorption rate was significantly higher in the patients, whereas the fractional reabsorption rate of calcium was significantly lower than in controls. In the patient group there was a significantly positive linear correlation between the increased tubular capacity for calcium reabsorption and the absolute proximal calcium reabsorption rate, but not between the increased capacity and the absolute distal calcium reabsorption rate. No significant differences were found in the renal tubular handling of sodium between patients and controls. Our results suggest that the increased capacity for tubular calcium reabsorption in primary hyperparathyroidism mainly is localized in the proximal tubule, and that the renal tubular handling of calcium and sodium in this disease differs from that in familial hypocalciuric hypercalcemia.

The Possible Role of Prostaglandin E2 in Urinary Stone Formation

To investigate the role of prostaglandin E2 in urinary stone formation, urinary prostaglandin E2 was measured by radioimmunoassay in 28 men with recurrent idiopathic urolithiasis (14 normocalciuric and 14 hypercalciuric patients) and 6 healthy male volunteers. Urinary prostaglandin E2 levels were significantly higher (p less than 0.01) in the hypercalciuric group than in the normocalciuric and healthy control groups, and they showed a positive correlation with urinary calcium excretion.Urinary prostaglandin E2 and calcium excretions in the hypercalciuric and normocalciuric groups were suppressed significantly by indomethacin. Creatinine clearance was not reduced by indomethacin. The results suggest that renal prostaglandin E2 may participate in calcium stone formation by regulating the renal tubular handling of calcium.

Renal handling of calcium and phosphate during mineralocorticoid administration in normal subjects.

The renal handling of calcium and phosphate in relationship to the renal handling of sodium was studied in 7 healthy male volunteers under steady state metabolic conditions during prolonged (10 days) mineralocorticoid treatment. Calcium excretion was reduced together with sodium excretion during the early phase of mineralocorticoid treatment, whereas it increased independent of sodium excretion following the escape. Phosphate excretion did not change throughout. These results suggest that when there is extracellular volume expansion without increase in sodium intake and/or excretion, there is a dissociation of calcium and sodium excretion, suggesting that extracellular volume can affect the renal tubular handling of calcium probably as a result of mechanism(s) operating in the distal nephron.

Effects of Phosphate and Calcium Infusion on Renal Phosphate Transport in the Dog

The effect of phosphate infusion on renal tubular handling of calcium and phosphate was examined in dogs which had been thyroparathyroidectomized (TPTX) immediately prior to the studies. Phosphate infusions in TPTX animals caused a small decrease in total and ultrafilterable plasma calcium, and decreased phosphate reabsorptive capacity in the proximal tubule and loop segment. Infusion of CaCl2 during phosphate loading to offset the fall in plasma calcium prevented the reduction in proximal phosphate reabsorptive capacity. However, between the proximal and distal sampling site, the reduction in phosphate reabsorptive capacity could not be prevented by CaCl2 administration. These data are consistent with the presence of two phosphate transport systems; one in the early proximal tubule, modulated by changes in plasma calcium level, and a second in the loop segment, which is independent of calcium. While the data suggest that the depression of proximal phosphate reabsorption during phosphate infusion may be secondary to the fall in plasma calcium concentration, they do not exclude a direct effect of infused phosphate on proximal phosphate reabsorption that may be antagonized by an opposing direct effect of the calcium infusion.

Diuretics and Calcium Metabolism

In this review the normal renal tubular handling of calcium is briefly described. A detailed examination follows of the sites and modes of action of furosemide and thiazide diuretics on renal calcium handling and overall calcium metabolism. The clinical applications of these effects are also considered. Finally, the use of diuretics with different tubular sites of action on calcium transport as probes to study disorders of calcium excretion is discussed.

Decreased calcium and magnesium urinary excretion during prostaglandin synthesis inhibition in the rat

The effect of endogenous renal prostaglandins on calcium and magnesium reabsorption was investigated. Renal tubular handling of calcium and magnesium was studied by clearance methods in anesthetized Sprague-Dawley and Brattleboro rats, either intact or thyroparathyroidectomized (ATPTX), before and during prostaglandin synthesis inhibition by meclofenamate, indomethacin, or piroxicam infusion. These three inhibitors had similar effects on calcium and magnesium excretion: A significant decrease in absolute and fractional excretions of both cations was observed in intact Sprague-Dawley rats, and in ATPTX rats of both strains, but not in intact Brattleboro rats. These results suggest an inhibitory effect of prostaglandins on vasopressin-, glucagon-, but not PTH-mediated calcium and magnesium reabsorption. This effect is likely to occur in the thick ascending limb of Henle, which is both a target site for these polypeptidic hormones, and a segment where the bulk of calcium and magnesium is reabsorbed.

Vitamin D deficiency and renal calcium transport in the rat.

To examine the role of vitamin D in the renal tubular handling of calcium, clearance studies were performed in three groups of rats: group A rats fed a standard vitamin D-deficient diet (Ca 0.45%, P 0.3%) for 6 wk, were hypocalcemic with secondary hyperparathyroidism; group B rats fed the same diet as in group A but with high calcium (Ca 1.4%) and 20% lactose, were normocalcemic and without secondary hyperparathyroidism; group C rats fed the same diet as in group A but supplemented with 25 U of vitamin D3 orally twice a week, were normocalcemic, vitamin D-replete, and euparathyroid. After thyroparathyroidectomy (TPTX), each rat was infused intravenously with an electrolyte solution that contained a fixed concentration of calcium (0-30 mM) with or without parathyroid hormone (PTH; 0.75 or 2.5 U/h) at a rate of 3 ml/h. Urinary calcium excretion and serum calcium concentrations were measured between 16 and 19 h of the infusion, and the apparent threshold of calcium excretion was determined. The threshold of calcium excretion was lower in vitamin D-deficient TPTX rats (groups A and B) than in vitamin D-replete TPTX rats (group C), and not different between group A and group B. Administration of PTH at a dose of 0.75 U/h increased the threshold of calcium excretion by approximately 0.6 mM in group C, but did not alter the threshold either in group A or group B. Administration of a higher dose of PTH (2.5 U/h) raised the threshold similarly in both group A and group B to the extent comparable with that in group C, when it was given 0.75 U/h of PTH. These results demonstrate that the renal threshold of calcium excretion is decreased in the vitamin D-deficient rats independent of the secondary hyperparathyroidism, and that the higher dose of PTH was necessary to raise the calcium threshold in vitamin D-deficient rats. Thus, present study indicates the presence of dual effects of vitamin D on renal tubular handling of calcium; the one is to facilitate renal calcium reabsorption and the other is to enhance the responsiveness of the tubule to PTH.

The Influence of Renal Prostaglandins on Urinary Calcium Excretion in Idiopathic Urolithiasis

Hypercalciuria is well recognized as an important factor in the cause of idiopathic calcium stone disease. Identification of the exact mechanism for the renal tubular handling of calcium has proved elusive, hence, treatment methods to alter the concentration of urine calcium in hypercalciuric stone formers have hitherto been non-specific. It is now well established that renal prostaglandins influence intrarenal hemodynamics and tubular electrolyte excretion. As the renal handling of sodium and calcium is intimately related, the possibility that the mechanism underlying hypercalciuria may be prostaglandin mediated was considered. Experiments were performed in conscious Sprague-Dawley rats (n = 10) to determine the changes in calcium excretion following prostaglandin synthetase inhibition with indomethacin. Calcium excretion was significantly reduced (p < 0.01), compared with control animals (n = 10). Further experiments were performed in anesthetized monkeys (Macaca fascicularis) to see if the inhibitory effect of indomethacin was reversible. Exogenous prostaglandin (PGE2) infusion resulted in a marked calciuretic response without producing changes in glomerular filtration rate or blood pressure. Forty-three hypercalciuric patients were treated with a prostaglandin inhibitor for periods ranging from 2 to 4 weeks, and all showed a significant fall in urinary calcium excretion to within the normal range. This clinical and experimental study suggests that prostaglandin (PGE2) is a hormone which determines the renal handling of calcium by influencing renal tubular function.

Effect of hypercalcemia on renal tubular handling of calcium and magnesium

Tubular calcium and magnesium transport was investigated in thyroparathyroidectomized rats following acute elevation of extracellular calcium concentration. Fractional urinary excretion of calcium increased from 0.2 to 8.3% and magnesium increased from 15 to 39%, while sodium increased modestly from 0.1 to 1.1%. Superficial proximal tubules, Henle's loop, and distal tubules were perfused in vivo to determine the segmental effects of hypercalcemia. Fractional calcium absorption within the loop of Henle was significantly less in the hypercalcemic rats (58%) compared with normal animals (86%). Magnesium transport was inhibited to a greater extent compared with calcium in the loop as the fractional reabsorption decreased from 78% in the normal rats to 35% in the hypercalcemic animals. Sodium absorption was inhibited by 8%. Absolute calcium and magnesium absorption within the superficial distal convoluted tubule increased about three- to four-fold with increased delivery to this segment. These data indicate that hypercalcemia inhibits calcium and magnesium transport relatively more than sodium absorption in the loop of Henle and that this action principally accounts for the increase in urinary excretion of these electrolytes.

Effect of Lithium on the Renal Tubular Handling of Calcium and Phosphate in Man

Effect of Lithium on the Renal Tubular Handling of Calcium and Phosphate in Man

Amiloride hydrochloride, a hypercalciuric diuretic.

SUMMARYAdministration of amiloride hydrochloride, a new potassium‐sparing diuretic, to six healthy volunteers for seven days produced significant hypercalciuria. No consistent interrelationship between the urinary excretion of calcium and magnesium, potassium or phosphorus was demonstrable. Three subjects with marked hypercalciuria showed no significant correlation between urinary calcium and sodium excretion, whereas one with marked hypercalciuria and two others with moderate or no hypercalciuria showed a significant correlation. A direct influence on the renal tubular handling of calcium, perhaps augmented by sodium diuresis, is suggested as a possible explanation for this hypercalciuric effect.