Hypercalciuria with calcium supplementation

The suppression of PTH secretion from the parathyroid gland that accompanies the constitutive activation of the CASR makes the disorder difficult to recognize and treat. In some cases, it has been reported that seizures can be intractable. The abnormal set point of calcium regulation complicates treatment with calcitriol and dietary calcium supplementation because the CASR expressed in the kidney controls calcium excretion. The constitutively activated CASR mutant induces hypercalciuria, which may compound the hypocalcemia (42). 

Stone formation may occur in those with elevated levels of urinary calcium, Mormally adults excrctc less than 200 mg of calcium in the urine per day, even with relatively high intakes of calcium, A fraction of the population absorbs more calcium than normal and excretes more calcium in the urine, resulting in hyper-calciuria. Hypercalciuria is defined as urinary excretion of calcium of more than 300 mg/day. About half of patients with calcium stones have hypercalciuria and may be calcium hyper absorbers. Persons with hypercalciuria are advised to limit their calcium intake to one serving of milk or cheese per day. They are also advised to limit their protein intake to the RDA. Their protein intake should be limited to minimize the caiciuric effect of protein. They are also advised to fnerense their water intake to produce 2 liters of urine per day and to avoid oxalate-containing foods. Persons with hypercalciuria and with a familial history of stones should not lake calcium supplements to raise their intake above the RDA. 

The rat has been used rather widely to study the relation between dietary protein, or acid salt feeding, and calcium loss. Barzel and Jowsey (19) showed that the rat fed a control diet supplemented with ammonium chloride excreted excessive urinary calcium, and experienced a concomitant loss of fat-free bone tissue. Draper, et al. (20) extending this work, reported an inverse relation between dietary phosphate and loss of bone calcium and dry, fat-free tissue. In subsequent studies (21), they reported that this process was accompanied by reduced serum calcium levels the high phosphorus, low calcium diet increased urinary calcium loss. Whereas, increasing the phosphorus content of the diet stopped the excessive urinary calcium loss. To test possible zinc loss that might result from this sort of acid salt feeding, Jacob and her coworkers (22) fed rats a supplement of ammonium chloride and then measured urinary zinc and calcium. The hypercalciuria occurred exclusive of an effect upon urinary zinc loss. 

Acidosis induced by salt feeding to humans influenced urinary calcium loss as effectively as feeding whole foods. Martin and Jones (25), for example, fed adult subjects a diet supplemented with ammonium chloride which resulted in marked hypercalciuria and an acidified urine. In a follow-up trial, feeding alkali as sodium bicarbonate, they also demonstrated that human hypercalciuria could be prevented by adding an alkaline supplement to the diet. 

Since unresolved nephrocaldnosis may lead to residual abnormalities in the kidney induding microscopic hematuria, hypercalciuria, and impaired tubular function [109, 113, 114], renal ultrasonography within a few months of initiating loop diuretics may be warranted [109,113]. If long-term diuretic therapy is needed, a thiazide diuretic alone or in combination with furosemide may reduce the risk of renal calcifications by decreasing urinary calcium and oxalate excretion [109, 111, 113,117,118]. However, two studies of premature infants failed to show a reduction in either urinary oxalate or calcium excretion when thiazides were added to furosemide therapy [116,119]. The lack of beneficial response may have been due to replacement of the infants sodium losses with large amounts of supplemental sodium. 

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