Calcium excretion effect

JAHNEN A, HEYNCK H, GERTZ B, CLABEN A, HESSE A (1992) Dietary fiber the effectiveness of a high bran intake in reducing renal calcium excretion. Urol Res, 20 3-6. 

Thiazide diuretics decrease urinary calcium excretion and may decrease bone turnover. However, their effects on bone mineral density and fracture rates have not been studied in controlled trials. Thiazide diuretics are not recommended solely for potential beneficial effects in osteoporosis. 

Multiple pharmacologic interventions are available for the treatment of hypercalcemia (Table 96-10). Furosemide 20 to 40 mg/day may be added to hydration once rehydration has been achieved to avoid fluid overload and enhance renal excretion of calcium. Although effective in relieving symptoms, hydration and diuretics are temporary measures that are useful until the onset of antiresorptive therapy thus hydration and antiresorptive therapy should be initiated simultaneously. 

Massey, L. K., Opryszek, M. S., No effects of adaptation to dietary caffeine on calcium excretion in young women, Nutrition Research, 10, 741, 1990. 

In a study with 40 healthy men and women, average age 63.7 years, who were randomized to either an alkali diet (meat plus fruits and vegetables) or an acid diet (meat plus cereal grains) (Jajoo and others 2006), altering the renal net acid excretion over a period of 60 days affected several biochemical markers of bone turnover and calcium excretion. The acidity of the diet had a significant effect on increasing NTX, a urinary marker of bone breakdown, and increasing the amount of calcium excreted in the urine. 

Many other dietary factors have been reported to affect calcium bioavailability. Phytate, fiber, cellulose, uronic acids, sodium alginate, oxalate, fat (only in the presence of steatorrhea), and alcohol have been reported to decrease calcium bioavailability (15). Lactose and medium chain triglyceride increase it (15). FTuoride also affects calcium retention primarily by stimulating bone formation thereby decreasing calcium excretion (33-38). The effects of fluoride on calcium utilization have been variable (34,38,39). 

The results of experiments conducted by MacKenzie and McCollum (15) indicate that the effect of dietary oxalic acid on the rat depends on the composition of the diet. There was no effect on rate of growth or calcium excretion of 50 g rats fed for 10 weeks a diet containing 0.6% calcium, 0.7% phosphorus, and optimum vitamin D, when levels of potassium oxalate up to 2.5% were fed. The percent bone ash on the 2.5% oxalate diet was somewhat lower than on the control diet. On a 0.35% calcium, 0.35% phosphorus, and vitamin D-free diet, 1.7% potassium oxalate resulted in restricted growth and bone formation of weanling rats. 

In the studies on humans there appeared to be decreased calcium balances when 200 g or more of spinach per day was included in the diet. In two of the studies in which women were fed spinach, calcium intakes were below the Recommended Dietary Allowance of 800 mg/day (37). Some studies were conducted for short period of a week or less, which may not be sufficient time to adjust to a change in diet. From measurement of calcium excretion in urine after a test meal, it was shown that the calcium in oxalate-containing vegetables was less well-absorbed than that of milk or of vegetables not containing oxalic acid. However, this would not necessarily affect calcium balance, since the total amount of calcium in the diet would have to be considered. The effect of a combination of oxalic acid and fiber on calcium bioavailability should be further investigated. 

Since the early 1970 s, research has been directed at identifying the mechanism by which the calciuria is induced. Attention was given first to the question of whether the elevated urinary calcium excretion was caused by an increase in the intestinal absorption of calcium. Results of calcium balance studies in human subjects showed that protein ingestion either had no effect on calcium absorption (4) or that the effect was insufficient to account for the calciuria (5j. Consequently, negative calcium balance is a frequent observation in human studies when high protein diets are fed, and this situation is not improved by high calcium intakes (4 ). 

The importance of insulin as a mediator of the hypercalciuric effect of arginine infusion was also evident from studies conducted in chronically diabetic rats, where diabetes was induced by strepto-zotocin (23). Animals were injected with streptozotocin prior to arginine infusion 100 mg/kg i.p. was given on the seventh day before, followed by 25 mg/kg six days before the arginine infusion and renal clearance studies. In contrast to non-diabetic controls, diabetic animals did not increase their urinary calcium excreted (per ml glomerular filtrate) in response to the arginine infusion, nor did the arginine stimulate insulin secretion. 

As anticipated, arginine infusion caused a large (221 percent) increase in calcium excretion in sham-operated animals. Parathyroidectomy had no effect on the calciuric response to arginine uri-ary calcium increases in PTX control and arginine-infused animals were 299 and 302 percent respectively. These results persisted when data were corrected for differences in GFR. The data illustrate that neither PTH activity nor secretion is involved in insulin impairment of renal calcium transport. 

While our data using this technique are still preliminary, we have observed that 25 yU/ml insulin inhibits the rate of calcium efflux from renal slices (28). This effect of insulin was gradually reduced at the higher concentrations of insulin. The effects of insulin on calcium exchange appear to be localized in the mitochondrial compartment. Further work is needed to determine whether insulin affects specific enzyme systems which are known to play a role in renal calcium transport, and which cellular or subcellular compartments are involved. This would substantially increase our understanding of the regulation of urinary calcium excretion, and of ways in which excessive loss of calcium by this route might be avoided. 

The effects of varying either the calcium or phosphorus level in conjunction with a high beef meal on the urinary calcium excretion of men are shown in Table IV. Urinary calcium excretion (total and ionized) was significantly elevated (P < 0.005) when the high protein beef meal contained 466 mg rather than 166 mg calcium. Increasing the phosphorus level from 308 mg to 700 mg in the high beef meal reduced both total and ionized calcium excretion in the urine, but the response was not statistically significant. Serum levels of calcium (ionized and total) and phosphorus were within normal limits and were unaffected by any of the dietary treatments. 

Table III. Postprandial Effects of Protein Level and Source on Urinary Calcium Excretion of Men...

Increasing the dietary calcium level in the high beef meal resulted in hypercalciuria. This effect was obtained in the absence of an altered insulin response which suggests that factors other than or in addition to serum insulin were involved in the control of urinary calcium excretion. 

The effect of zinc toxicity on the calcium balance of young rats is presented in Table V. Marked increases in the fecal excretion of calcium was noted in the zinc-fed rats, and the overall effect of zinc toxicity was a substantial decrease in the apparent retention of calcium. The effects of zinc on calcium retention were noted as early as one week of the experimental period. 

Prentice, A., Jaqou, L. M., Cole, T. J., Stirling, D. M., Dibba, B., and Fairweather-Tait, S. (1995). Calcium requirements of lactating Gambian mothers Effects of a calcium supplement on breast-milk calcium concentration, maternal bone mineral content, and urinary calcium excretion. Am. J. Clin. Nutr. 62, 58-67. 

Certain foreign compounds may cause the retention or excretion of water. Some compounds, such as the drug furosemide, are used therapeutically as diuretics. Other compounds causing diuresis are ethanol, caffeine, and certain mercury compounds such as mersalyl. Diuresis can be the result of a direct effect on the kidney, as with mercury compounds, which inhibit the reabsorption of chloride, whereas other diuretics such as ethanol influence the production of antidiuretic hormone by the pituitary. Changes in electrolyte balance may occur as a result of excessive excretion of an anion or cation. For example, salicylate-induced alkalosis leads to excretion of Na+, and ethylene glycol causes the depletion of calcium, excreted as calcium oxalate. 

Parathyroid hormone (PTH) is an 84-amino acid peptide secreted by the parathyroid glands, and is the principal regulator of extracellular calcium levels [44, 45]. The effects of PTH on extracellular calcium are mediated directly or indirectly through effects on bone, kidney, and intestine. A decrease in extracellular calcium causes an increase in PTH secretion. As a consequence, the rise in PTH levels causes increased bone resorption and the release of calcium from bone, decreased calcium excretion by the kidney, and increased intestinal calcium absorption. The therapeutic application of PTH has centered on the bone effects as an anabolic treatment for osteoporosis. PTH increases the activity of both osteoblasts (which form bone) and osteoclasts (which mediate bone resorption). The desirable anabolic effects of PTH on osteoblasts appear to be highly dependent on dose schedule and the duration of daily exposure. 

Calcium-sparing diuretics. Diuretics that result in a relatively low rate of excretion of calcium. The sparing effect on calcium can be beneficial in hypocalcaemia. The thiazides and potassium-sparing diuretics are considered to be calcium-sparing diuretics. The thiazides cause a net decrease in calcium lost in urine the potassium-sparing diuretics cause a net increase in calcium lost in urine, but the increase is much smaller than that associated with other diuretic classes. By contrast, loop diuretics promote a significant increase in calcium excretion. This can increase risk of reduced bone density. 

Calcitonin (see below). When the hypercalcaemia is at least partly due to mobilisation from bone, calcitonin can be used to inhibit bone resorption, and it may enhance urinary excretion of calcium. The effect develops in a few hours, and responsiveness may be lost over a few days (but may sometimes be restored by an adrenal steroid). 

Four children with the nephrotic syndrome developed transient hypercalciuria and intraluminal calcification in renal histopathological specimens without radiological evidence of renal calcification. These children were resistant to corticosteroids and were receiving furosemide plus albumin for the management of edema (10). This result stresses the pervasive effect of furosemide, and probably all loop diuretics, in increasing urinary calcium excretion, with resultant nephrocalcinosis. Whenever possible, steps should be taken to limit the hypercalciuric effect of loop diuretics. Such maneuvers could include limiting the sodium content of the diet and/or combining the loop diuretic with a thiazide diuretic. 

After persistent hypercalciuria, osteopenia can develop, causing metabolic bone disease, pathological fractures, and immobilization. Hypercalciuria can also lead to nephrolithiasis and nephrocalcinosis, factors that can impair renal function. Intravenous chlorothiazide has been successfully used for its hypocalciuric effect, with remarkable effect over a period of 6 months in a 13-year-old child who had received parenteral nutrition for 6 years. Calcium excretion and tubular reabsorption of phosphate returned to normal (48). What is not clear from this study is whether the drug actually has a positive long-term beneficial effect on metabolic bone disease. 

Diuretics have been shown to have variable effects in relationship to urinary calcium excretion and supersaturation, most notably including loop diuretic induced hypercalciuria and attenuation of urinary calcium excretion by thiazide diuretics. The factors contributing to nephrotoxicity are most commonly associated with multiple factors that favor calcium salt or uric acid deposition at the tubulo-interstitial level. Management of renal stone formation and nephrocalcinosis therefore presents a unique clinical challenge, balancing factors that increase risk for abnormal calcium salt deposition or crystallization, and factors that reduce this risk. 

A striking and unexpected outcome of the Cadmibel study was the clear-cut interference of fhe low-level Cd exposure with calcium metabolism. For example, when urinary Cd excretion increased twofold, serum alkaline phosphatase activity and urinary calcium excretion rose by 3-4% and 0.25 mmol/24h respectively [142]. The dose (CdU)-response rate of increased calciuria (>9.8 mmol/24h) suggested a 10% prevalence of hy-percalciuria when CdU exceeded 1.9 pg Cd/24h [38]. Hypercalciuria should be considered an early adverse tubulotoxic effect, because it may exacerbate the development of osteoporosis, especially in the elderly. A prospective study from 1992-1995 (median follow-up of 6.6 years) in the above-mentioned Cadmibel subcohort from the rural area showed for a two-fold increase in urinary Cd a significant (p<0.02) decrease of 0.01 g/ cm in forearm bone density in post-menopausal women. In addition, the relative risks associated with doubled urinary Cd were 1.73 (95% Cl 1.16-2.57 p=0.007) for fractures in women and 1.60 (0.94-2.72 p=0.08) for height loss in men. Cadmium excretion in the four... 

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