Urinary calcium

The overall effect in most animals is to stimulate intestinal absorption of calcium with a concomitant increase in semm calcium and a reduction in parathyroid hormone (PTH). Modest hypercalcemia allows the glomerular filtration rate to remain stable and hypercalciuria to occur because of increased filtered load of calcium and reduction of tubular resorption of calcium with reduced PTH. However, with further increases in semm calcium, the glomerular filtration rate decreases, resulting in an even more rapid increase in semm calcium and the subsequent fall in urinary calcium. 

When these drugs are given to the female patient with inoperable breast carcinoma, tire nurse evaluates the patient s current status (physical, emotional, and nutritional) carefully and records tire finding in tire patient s chart. Problem areas, such as pain, any limitation of motion, and the ability to participate in tire activities of daily living, are carefully evaluated and recorded in tiie patient s record. The nurse takes and records vital signs and weight. Baseline laboratory tests may include a complete blood count, hepatic function tests, serum electrolytes, and serum and urinary calcium levels. The nurse reviews these tests and notes any abnormalities. 

Knapen, M.H.J., Kon-Siong, G.J., and Hamulyak, K. et al. (1993). Vitamin K-induced changes in markers for osteoblast activity in urinary calcium loss. Calcified Tissue International 53, 81-85. 

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. 

Thiazide diuretics increase urinary calcium reabsorption two controlled trials demonstrated small increases in bone mass over placebo. 

Prescribing thiazide diuretics solely for osteoporosis is not recommended but is a reasonable choice for patients with osteoporosis who require a diuretic and for patients on glucocorticoids with a 24-hour urinary calcium excretion >300 mg. 

In attempting to reconcile these findings, it should be pointed out that rats may not be appropriate models for the study of calcium metabolism in humans. Unlike humans, the rat does not undergo epiphyseal plate closure and does not have a significant haversian remodeling sequence (21) Furthermore, rats excrete only l-270 of their calcium intake in their urine whereas humans excrete approximately 20-30% or more. This fact is especially significant, since most of the known effects of phosphates on calcium retention in humans are effected by alterations in urinary calcium. 

Increasing the level of phosphorus intake has long been known to exert a hypocalciuretic effect (22,23). Bell et al. (24) suggested that this effect may be secondary to an increase in PTH secretion, but phosphorus supplementation has been reported to decrease urinary calcium even in parathyroidectomized rats (14). Goldsmith and coworkers (25) found phosphate supplements to cause an increase in PTH... 

We have conducted two human metabolic studies (5,6) to compare the effects of increasing phosphorus intake on calcium utilization in healthy young adults maintained at low (ca. 400 mg/day) and high (ca. 1200 mg/day) levels of calcium intake. Increasing dietary phosphorus, as orthophosphate, caused a slight reduction in fecal calcium and a substantial reduction in urinary calcium losses (Table III). 

Figure 5. The areas above the measured calcium and measured phosphate retention curves represent the percent of the intravenously administered calcium and phosphate that was lost in the urine. The combined percent losses (Ca + P) are minimized at the intercept of the curves. The dotted line represents an assumed endogenous fecal loss of 20% of the infused calcium added to the measured urinary calcium losses. The Ca/P ratio that minimizes the percent calcium and phosphate losses is then approximately 3.0. (Reproduced with permission from Ref. 4. Copyright 1983 American Society for Parenteral and Enteral Nutrition.)...

Numerous studies of dietary protein-induced urinary calcium loss have appeared, in which the quantitative effect of protein upon calcium has been investigated. Anand and Linkswiler (12) reported that feeding a high-protein (150 g/d) diet to college students nearly doubled their calcium output compared with their output when on a low-protein (42 g/d) diet. Most of the calcium was lost in the urine with only very small increases in fecal losses. 

The bone becomes depleted of calcium salts when the urine is acidic over a relatively long period. This was shown by Goto (17) who fed rabbits large doses of hydrochloric acid. He then showed that urinary calcium loss occurred in concert with a marked reduction in mass of the skeletal system, and also that the total non-fat dry weight of bone decreased,implying a loss of bone matrix. A dose-dependent, dietary acid induced loss of labelled calcium from rat bone has been reported by Thorn and his coworkers (18). They demonstrated that in response to graded doses of ascorbic acid, cells in tissue culture, and bones in whole animals fed such doses were depleted of the labelled calcium. 

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. 

In a feeding study with one male subject, a calciuretic effect prevailed when an acidic, rice-enriched diet was fed compared with a potatoe diet, in studies with women, Bogert and Kilpatrick (24) showed that feeding subjects an acidic diet resulted in elevated urinary calcium, whereas an alkaline diet induced a decline in urinary calcium. 

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. 

Figure 1. Effect of soy bean and meat diets on average urinary total titratable acidity (TTA) and calcium. Upper two curves represent TTA lower two curves, urinary calcium. Bars indicate...

When subjects ate the meat diet, mean calcium losses in the urine increased significantly in all subjects (P<0.02). In the soy period, the daily urinary calcium loss averaged from 1 to 7.5 mEq with an average of 4.23, but in the meat period, the daily loss ranged from 2 to 10.5 mEq with an average of 5.07. 

In six subjects, urinary calcium excretion during the soy period peaked by day 5, and began to decrease, but in three subjects, it began to decline by day 2. Two subjects did not show any rise in urinary calcium. In one subject the value on day 5 was lower than that on day 2 thereafter, it resumed its upward trend. For all subjects, the kinetics of the rise and fall to near initial values suggested that an equilibrium may have been established. 

Mean values of urinary calcium during meat eating exceeded the soy values at comparable time points for all subjects except one. 

The meat diet resulted in markedly greater titratable acid and calcium excretion compared with the soy diet (P<0.02). This occurred despite the fact that each diet contained the same amounts of protein, calcium, phosphorus, and sulfur. Increased urinary calcium excretion in subjects accompanied this increased output of TTA (P<0.02) ... 

Acidosis resulting from endogenous acid production also induces urinary calcium loss. The kidney responds to such acid production, as in the case of dietary acid, by excreting more calcium. 

Feeding human subjects meat-rich diets has been clearly and repeatedly associated with elevated urinary acid and calcium loss. Anand, et al. (12) fed college men low, medium, and high-protein diets. Fecal calcium changed less than 15%, whereas urinary calcium losses accounted for the major loss of calcium. Calcium loss and meat protein intake correlated directly. Johnson, et al. (34) reported that women showed a similar response when fed such diets. 

In yet another study, Hegsted, et al. (37) found that feeding a high protein level occasioned an increase in urinary calcium. 

Bricker et al. (30) reported that there were no statistically significant differences between the calcium balances of eight women on cocoa and non-cocoa diets. The women were studied for three to seven 4-day periods. Calcium intake was 670 mg/day with the addition of milk and 679 and 755 mg/day with the addition of milk and cocoa. Five levels of cocoa, supplying from 5.6-52.6 g/day, were tested. These amounts would likely contain from 25-280 mg of oxalic acid, which was not nearly as much as was added when spinach was fed. With the inclusion of cocoa in the diet, the urinary calcium fell and fecal calcium rose. There were also increases in the fecal excretion of dry matter and nitrogen. 

Figure 8. Urinary calcium of male adults consuming a basal diet (1), milk diet (2), amaranthus diet (3), and a milk + amaranthus diet (4). Adapted from Ref. 33.

This paper summarizes our evidence that the mechanism involves protein stimulation of insulin secretion, followed rapidly by insulin inhibition of renal calcium reabsorption. In humans, urinary calcium was proportional to peak postprandial insulin levels in several experiments, after either protein or sucrose was fed. 

From preliminary in vitro experiments using rat renal slices, it appears that the hormone directly affects renal calcium transport. If insulin is the mediator of the hypercalciuria, it might be possible to reduce urinary calcium loss by lowering the intake of in-sulinogenic foods. This would be especially important in those individuals with a marked calciuric response to such foods. 

For more than forty years, it has been known that increasing the protein content of the diet causes an increase in urinary calcium excretion (1, 2). There is, in fact, a direct correlation between urine calcium output and dietary protein level, so that excretion is 800 percent higher if dietary protein is increased from 6 g per day to 560 g per day (3 ). This relationship between urinary calcium and protein ingestion is not affected by the level of dietary calcium, and is evident even when severely calcium-deficient diets are consumed (3). 

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 ). 

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