Hypercalciuria, or excessive urinary calcium excretion, is the most common identifiable cause of calcium kidney stone disease. Idiopathic hypercalciuria is diagnosed when clinical, laboratory, and radiographic investigations fail to delineate an underlying cause of the condition. Secondary hypercalciuria occurs when a known process produces excessive urinary calcium.
The following are the most common types of clinically significant hypercalciuria:
Renal phosphate leak hypercalciuria (also known as absorptive hypercalciuria type III)
Renal leak hypercalciuria
Resorptive hypercalciuria - This is almost always caused by hyperparathyroidism
Signs and symptoms
The morbidity of hypercalciuria is related to 2 separate factors; ie, kidney stone disease and bone demineralization leading to osteopenia and osteoporosis.
Kidney stones are extremely painful because of the stretching, dilating, and spasm of the ureter and kidney caused by the acute obstruction.
Hypercalciuric stone formers have been demonstrated to have a lower average bone mineral density than non–stone formers matched for age and sex. Moreover, compared with normocalciuric stone formers, hypercalciuric patients have an average bone density that is 5-15% lower. 
In children, hypercalciuria is often associated with some degree of hematuria and back or abdominal pain and is also sometimes associated with voiding symptoms.
Microcrystallization of calcium with urinary anions has been suggested to lead to injury of the uroepithelium in children with hypercalciuria. Consequently, when taking the history of the illness, attempt to identify symptoms relating to the urinary tract, paying special attention to the following signs and symptoms:
Change of urinary appearance
Isolated or recurrent urinary tract infections 
Vesicourethral reflux 
See Clinical Presentation for more detail.
Initial blood tests, such as serum calcium, creatinine, and phosphate studies, should be performed to identify patients at risk for hyperparathyroidism, renal failure, and renal phosphate leak. Once hyperparathyroidism has been excluded, diagnosis can be made using either a traditional or simplified workup. 
In addition, imaging studies may be helpful in identifying underlying renal abnormalities or nephrolithiasis.
In the traditional workup, an effort is made to formally study the exact cause of the hypercalciuria. Using this approach, a calcium-loading test is performed; results include the following:
Absorptive hypercalciuria - After calcium loading, periodically obtained urine samples tend to show a great increase in the patient’s urinary calcium excretion
Renal leak hypercalciuria - After calcium loading, patients do not demonstrate as large an increase in urinary calcium as do those with absorptive hypercalciuria
Complete a medical history
Carry out initial blood and 24-hour urine testing
Identify hypercalciuric patients
Check hypercalcemic patients for hyperparathyroidism with parathyroid hormone (PTH) levels; consider a thiazide challenge test if the PTH level alone is inconclusive
Check hypophosphatemic patients for hyperphosphaturia and possible renal phosphate leak hypercalciuria; verify the diagnosis by determining of the vitamin D-3 level or with a clinical trial of orthophosphate therapy
Start a therapeutic trial of dietary modification treatment
Repeat the blood and 24-hour urine tests
See Workup for more detail.
The following are recommendations in the dietary treatment of hypercalciuria:
Limit dietary oxalate, especially when calcium intake is reduced; high oxalate levels are found in strong teas; nuts; chocolate; coffee; colas; green, leafy vegetables (eg, spinach); and other plant and vegetable products
Avoid excessive purines and animal protein (< 1.7 g/kg of body weight)
Reduce sodium (salt) and refined sugar to the minimum possible
Increase dietary fiber (12-24 g/day)
Limit alcohol and caffeine intake
Increase fluid intake, especially water (sufficient to produce at least 2 L of urine per day)
Medical therapy is used to treat hypercalciuria whenever dietary treatment alone is inadequate, ineffective, unsustainable, or intolerable for the patient.  Medications used in the treatment of hypercalciuria include the following
Diuretics - Thiazides, indapamide, and amiloride
Orthophosphates - Neutral phosphate
Bisphosphonates - Alendronate
Calcium-binding agents - Sodium cellulose phosphate; rarely used
Hypercalciuria, or excessive urinary calcium excretion, occurs in about 5-10% of the population  and is the most common identifiable cause of calcium kidney stone disease. Indeed, about 80% of all kidney stones contain calcium, and at least one third of all calcium stone formers are found to have hypercalciuria when tested. Hypercalciuria also contributes to osteoporosis. (Other significant causes of kidney stones include hyperoxaluria, hyperuricosuria, low urinary volume, and hypocitraturia.)
Hypercalciuria can be classified as idiopathic or secondary. Idiopathic hypercalciuria can be diagnosed when clinical, laboratory, and radiographic investigations fail to delineate an underlying cause. Secondary hypercalciuria occurs when a known process produces excessive urinary calcium. (See Pathophysiology, Etiology, and Workup.)
Elevated urinary calcium occurs by 1 of 3 primary mechanisms, as follows:
The filtered load of calcium is abnormally increased without an adequate compensatory increase in tubular calcium reabsorption
The filtered calcium load is normal but tubular calcium reabsorption is reduced
The filtered load is increased and the reabsorbed load is reduced
A good screening test for hypercalciuria compares the ratio of urinary calcium to creatinine. To validate the screening test, an accurately timed urinalysis should be used to confirm any positive screens. (See Workup.)
Hypercalciuria is defined as urinary excretion of more than 250 mg of calcium per day in women or more than 275-300 mg of calcium per day in men while on a regular unrestricted diet. It can also be defined as the excretion of urinary calcium in excess of 4 mg/kg of body weight per day or as a urinary concentration of more than 200 mg of calcium per liter.
An alternate definition of hypercalciuria is daily urinary excretion of more than 3 mg of calcium per kilogram of body weight or more than 200 mg of calcium per day, while on a restricted diet (400 mg calcium and 100 milliequivalent [mEq] sodium). Table 1, below, outlines the various definitions of hypercalciuria based on a regular or restricted diet.
Table 1. Definitions of Hypercalciuria (Open Table in a new window)
|Regular diet (unrestricted)||
Women: Urinary excretion >250 mg calcium (6.2 mmol/24 h)
Men: Urinary excretion >275-300 mg calcium (7.5 mmol/24 h)
Urinary excretion >4 mg calcium (0.1 mmol) per kilogram of body weight per day
Urinary concentration >200 mg calcium per liter
|Restricted diet (400 mg calcium, 100 mEq sodium)||Urinary excretion >200 mg calcium per day|
|Urinary excretion >3 mg calcium per kilogram of body weight per day|
Limitations of hypercalciuria definitions
Optimal levels of urinary calcium have not been determined. Several experts, including the author of this article and Dr. Gary Curhan of Harvard University, have suggested that the current definitions of hypercalciuria and several other 24-hour urinary chemistries are inadequate and may not be reliable when applied to nephrolithiasis. Available definitions are limited by the occasional inclusion in research investigations of recurrent stone formers in the healthy group of study subjects and by poorly defined controls.  In addition, the parameters and ranges are not optimized from the point of view of kidney stone disease or production.
The data from several large databases (including the Nurses' Health Study and the Health Professional Follow-up Study) indicate that, with the current definition of hypercalciuria, a substantial proportion of controls would be defined as abnormal. The relative risk of stone production appears to be continuous, along a sliding scale, rather than dichotomous with a single arbitrary level that differentiates healthy people from those who form stones.
Therefore, although the gross total 24-hour urinary calcium excretion remains useful, the urinary calcium concentration is probably a more reliable dynamic indicator of stone formation risk.  Further study is needed to confirm these conclusions and to possibly establish better 24-hour urine reference ranges for calcium and other metabolic stone–risk chemistries. (See Workup.)
Clinically significant hypercalciuria
The following are the most common types of clinically significant hypercalciuria, although evidence suggests that this classic differentiation is insufficient to explain all of the cellular and genetic variations that have been noted in the condition  :
Renal phosphate leak hypercalciuria (also known as absorptive hypercalciuria type III)
Renal leak hypercalciuria
It is uncertain whether these different types of hypercalciuria are truly separate and distinct entities or are instead just the extremes of a single, unified process. Although the answer to this question is not currently known, the evidence and the consensus opinion lean toward the unified theory. In reality, other than for research purposes, this question has little impact clinically, because ultimately whatever therapy works is required. Table 2, below, provides simple test guidelines for specific diagnoses of hypercalciuria. (See Treatment and Medication.)
Table 2. Hypercalciuria Simplified Test Guideline (Open Table in a new window)
Urinary Calcium on 400-mg Calcium Diet
(Normal = < 200 mg/24 h)
Fasting Calcium/Creatinine Ratio
(Normal = < 0.11)
Post–Calcium Load Calcium/Creatinine Ratio
(Normal = < 0.20)
|Absorptive type I||High||Normal||High|
|Absorptive type II||Normal||Normal||High|
|Absorptive type III (renal phosphate leak)||High||High||High|
Absorptive hypercalciuria is by far the most common cause of excessive urinary calcium. About 50% of all calcium stone formers have some form of absorptive hypercalciuria, which is caused by an increase in the normal gastrointestinal absorption of calcium, overly aggressive vitamin-D supplementation, or excessive ingestion of calcium-containing foods (milk-alkali syndrome). Calcium absorption occurs mainly in the duodenum and normally represents only about 20% of the ingested dietary calcium load. 
Increased intestinal calcium absorption produces a corresponding increase in serum calcium levels. Typically, serum parathyroid hormone (PTH) is low or in the low-normal range in absorptive hypercalciuria, because the serum calcium level is generally high.
Mild or moderate absorptive hypercalciuria can usually be controlled solely with dietary measures, but medical therapy is required in severe and resistant cases.
Absorptive hypercalciuria type I is a relatively rare condition, generally characterized by elevated urinary calcium and calcium/creatinine levels except while fasting.
A variant of absorptive hypercalciuria type I exists in which fasting hypercalciuria can occur due to excess serum vitamin D-3. This vitamin D–dependent variant can be diagnosed with the finding of increased serum vitamin-D levels and with correction of the fasting hypercalciuria with a trial of ketoconazole therapy. (Ketoconazole is a potent P450 3A4 cytochrome inhibitor that reduces circulating vitamin D-3 levels by 30-40%.)
As many as 50% of all patients with absorptive hypercalciuria type I may have increased levels of vitamin D-3. Other causes of fasting hypercalciuria can be identified by elevated PTH levels (renal leak and resorptive hypercalciuria) or by increased urinary phosphate levels with hypophosphaturia (renal phosphate leak calciuria, also called absorptive hypercalciuria type III).
Absorptive hypercalciuria type I represents an extremely efficient intestinal calcium absorption mechanism. Bone density is usually normal, because abundant calcium is available for bone deposition, and PTH levels are normal or low. In some cases, however, the urinary calcium excretion is even greater than the amount absorbed, resulting in a net negative calcium balance and possible decrease in bone density, which is the opposite of what would be expected. Researchers think that this could be due to elevated serum vitamin-D levels or may be the result of an increased sensitivity to vitamin D and its metabolites.
This is a less severe form, and most common variety, of absorptive hypercalciuria. It usually responds to moderate dietary calcium restriction. Fasting hypercalciuria is not present in this disorder.
Absorptive hypercalciuria type III, also called renal phosphate leak hypercalciuria, is a vitamin D–dependent variant of absorptive hypercalciuria. This condition, a relatively uncommon cause of hypercalciuria, should be suspected in any patient with hypercalciuria who has a low serum phosphate level. A serum phosphate level of less than 2.9 mg/dL has been suggested as sufficient to raise the suspicion of renal phosphate leak hypercalciuria.
The etiology is an obligatory and uncontrolled loss of phosphate in the urine due to a renal defect. This produces hypophosphatemia, which stimulates the renal conversion of 25-hydroxyvitamin D to the much more active 1,25-dihydroxyvitamin D-3 (calcitriol, vitamin D-3). Vitamin D-3 increases intestinal phosphate absorption to correct the low serum phosphate levels. However, it also simultaneously increases intestinal calcium absorption. This extra calcium eventually is excreted in the urine. The diagnosis is confirmed by the following findings:
Low serum phosphate
High urinary phosphate
High serum vitamin D-3
Normocalcemia and normal PTH levels
Renal leak hypercalciuria
The etiology is a defect in calcium reabsorption from the renal tubule that causes an obligatory, excessive urinary calcium loss. This results in hypocalcemia, which causes an elevation in the serum PTH. This secondary hyperparathyroidism raises vitamin-D levels and increases intestinal calcium absorption. Essentially, this means that, even in cases of undeniable renal leak hypercalciuria, an element of absorptive hypercalciuria can be present.
The diagnosis is relatively easy. Any patient who fails to control their excessive urinary calcium on dietary measures alone and who demonstrates relatively high serum PTH levels without hypercalcemia or hypophosphatemia probably has renal leak hypercalciuria.
The calcium/creatinine ratio tends to be high in renal leak hypercalciuria (>0.20), and the occurrence of medullary sponge kidney is more likely than in other types of hypercalciuria.
Renal leak hypercalciuria is generally not amenable to therapy with dietary calcium restrictions, because of the obligatory calcium loss, which can easily lead to bone demineralization, especially if oral calcium intake is restricted.
Resorptive hypercalciuria is almost always due to hyperparathyroidism. This generally accounts for 3-5% of all cases of hypercalciuria, although some reports have indicated an incidence as high as 8%. Increased PTH levels cause a release of calcium from bone stores.
In addition, resorptive hypercalciuria increases calcium absorption from the digestive tract by raising vitamin D-3 levels and decreases renal excretion of calcium by stimulating calcium reabsorption in the distal renal tubule. Eventually, the hypercalcemia overcomes this renal calcium–conserving quality and results in an increased net loss of calcium through the urine (hypercalciuria).
Hyperparathyroidism does not always result in calcium-stone disease. The reason for this is unclear but may reflect urinary volume and optimal levels of other urinary metabolites, such as oxalate, uric acid, sodium, phosphate, citrate, urinary volume, and serum vitamin D-3. In some cases, the vitamin D-3 level has been suggested to be responsible for determining which patients with hyperparathyroidism actually develop kidney stones. This apparently reasonable hypothesis remains unproved, however, and the current evidence suggests that vitamin-D levels cannot be the only reason that some patients with hyperparathyroidism do not develop stones.
Hyperparathyroidism produces a lower urinary calcium excretion for the patient’s serum calcium level than does hypercalcemia from other causes. In other words, for any level of serum calcium, patients with hyperparathyroidism have lower urinary calcium excretion than do patients with hypercalcemia who have normal PTH levels. This is due to the calcium-conserving effect of PTH on the kidneys.
Diagnosis and treatment
Hyperparathyroidism should be suspected in calcium stone–forming patients with significant hypercalciuria, even in those with only mild hypercalcemia. Failure to identify a curable cause of osteoporosis and calcium nephrolithiasis can be easily avoided just by checking the parathyroid hormone level routinely in hypercalciuric patients with relatively high serum calcium levels. 
Patients with hyperparathyroidism who have parathyroid surgery and subsequently demonstrate normal urinary calcium levels are still at risk for developing stones at about the same rate as other calcium-stone formers. Therefore, retesting with 24-hour urine determinations is recommended for calcium-stone formers even after successful parathyroid surgery has normalized their serum calcium levels. Urinary cyclic adenosine monophosphate (cAMP) can be used as a substitute for serum PTH level determinations to monitor patients who have already been diagnosed.
Urinary excretion of calcium is the result of the complex interplay of the gastrointestinal tract, the kidney, and bone and is regulated by multiple hormones. Hypercalciuria is believed to be a polygenic trait and is significantly influenced by diet.
Idiopathic hypercalciuria is the most common metabolic abnormality in patients with calcium kidney stones. Subjects with idiopathic hypercalciuria have a generalized increase in calcium turnover, which includes increased gut calcium absorption, decreased renal calcium reabsorption, and a tendency to lose calcium from bone. Despite the increase in intestinal calcium absorption, a negative calcium balance is commonly seen in balance studies, especially in patients on a low-calcium diet. The mediator of decreased renal calcium reabsorption is unclear; it is not associated with either an increase in filtered renal calcium or altered parathyroid hormone (PTH) levels.
An increased incidence of hypercalciuria is observed in first-degree relatives of individuals with idiopathic hypercalciuria, but it appears to be a complex polygenic trait with a large contribution from diet to expression of increased calcium excretion.
Increased tissue vitamin D response may be responsible for manifestations of idiopathic hypercalciuria in at least some patients. [10, 11] Moreover, deficiency in the enzyme that inactivates 1,25(OH)2D, 1,25(OH)2D-24 hydroxylase causes elevated vitamin D, hypercalciuria, nephrocalcinosis, and kidney stones.  Furthermore, dysregulation of the calcium-sensing receptor ̶ Claudin-14 axis likely contributes to the development of hypercalciuria. [13, 14, 15]
Intestinal adaptation occurs with long-term, consistent calcium intake. This means that patients with persistently low dietary calcium increase their intestinal calcium absorption, and those with a high calcium intake show a corresponding decrease in intestinal absorption.
Fractional calcium absorption decreases with larger calcium loads, probably due to saturation of active absorption pathways. It plateaus at about 500 mg of calcium for most people. This means that an oral calcium dose is absorbed better if administered in small, divided portions rather than in a single large calcium bolus. In general, each additional 100 mg of daily dietary calcium ingestion increases urinary calcium levels by 8 mg/day in a healthy population but raises urinary calcium levels by 20 mg/day in hypercalciuric patients.
When properly evaluated, 97% of hypercalciuric patients can be classified according to etiology. Causes of hypercalciuria that need to be considered include the following:
Renal tubular acidosis
Sarcoidosis and other granulomatous diseases
Vitamin D intoxication
Albright tubular acidosis
Various paraneoplastic syndromes
Induced hypophosphatemic states
Metastatic tumors (especially to bone)
As the name implies, the cause of idiopathic hypercalciuria is not known. Several theories have been published, and some data supports certain aspects of these theories; however, these theories cannot yet be uniformly applied to a large patient population. Studies that examined metabolic balance have reported increased absorption of calcium from the intestine. In some instances, this process has been shown to be independent of vitamin D or a result of increased gut sensitivity to vitamin D.
In other patients with hypercalciuria, the proportion of calcium excreted into the urine is higher than normal, regardless of dietary intake of calcium. In fact, some patients have been found to have higher than normal urinary calcium despite lower than normal dietary intake, suggesting decreased renal tubular reabsorption. This renal tubular leak is possibly a result of a mutational defect in 1 or more ion channels.
Another proposed mechanism involves an imbalance of calcium deposition and reabsorption in bone that is independent of PTH or vitamin D. In addition, a combination of these factors may contribute to the high amounts of urinary calcium observed in patients with idiopathic hypercalciuria.
Molecular genetics and other research have indicated potential lines of future investigation into the nature of hypercalciuria. For example, dysregulation of the calcium-sensing receptor ̶ Claudin-14 axis, as well as polymorphism in the regulatory region controlling expression of the calcium sensing ̶ receptor gene, may contribute to increased calcium excretion. [13, 14] More than 60 activating mutations in the calcium-sensing receptor have been identified to cause autosomal dominant hypocalcemic hypercalciuria. 
An interesting study in specially prepared transgenic mice suggests the possible importance of the gene CLCN5, which encodes ClC5 (a renal chloride channel located exclusively in the kidney), to the development of hypercalciuria. The transgenic mice were produced using an antisense ribozyme targeted against ClC5 so that these mice lacked ClC5 activity.  This mouse model is similar to Dent disease in humans, which is a rare, heritable X-linked disorder with reduced ClC5 activity that is characterized by absorptive hypercalciuria, nephrocalcinosis, nephrolithiasis, low ̶ molecular weight proteinuria, Fanconi syndrome, and renal failure. In Dent disease, the nephrolithiasis, hypercalciuria, and nephrocalcinosis are eliminated with a renal transplant from a healthy individual, confirming the renal cause of these problems. 
Other promising lines of research involve overexpression of vitamin D receptors and deficiencies in various renal tubular enzymes.
Pregnancy has long been thought to increase the incidence of urinary stones and hypercalciuria. Healthy, non–stone-producing pregnant women have been found to have hypercalciuria during all 3 trimesters. In addition, urinary oxalate, magnesium, and citrate levels have been found to increase during pregnancy. This suggests that the overall risk of nephrolithiasis during pregnancy may not be increased substantially, as levels of urinary stone promotors and inhibitors have both been found to rise.
A study suggests that calcium supplementation, with or without calcitriol, does not increase the risk of calcium urolithiasis significantly in healthy (non–stone-forming) postmenopausal women even if they have increased urinary calcium excretion.  The study, which involved healthy postmenopausal women (not calcium-stone formers), showed that those women who were administered calcium supplements alone did not demonstrate any significant increase in their urinary calcium excretion.
Those who were administered calcium and calcitriol did have a significant increase in their urinary calcium levels. However, this did not result in any increase in overall stone risk or calcium oxalate activity product, due in part to a simultaneous decrease of about 20% in urinary oxalate levels. Theoretically, a thiazide diuretic would reduce the urinary excretion of calcium and could be of some therapeutic benefit for this group at risk for osteoporosis.
Many cases of absorptive hypercalciuria involve elevated vitamin-D levels.  Vitamin D increases small-bowel absorption of calcium and phosphate, enhances renal filtration, decreases PTH levels, and reduces renal tubular calcium absorption, which ultimately leads to hypercalciuria. An elevated vitamin-D level accounts for the finding of fasting hypercalciuria in some cases of absorptive hypercalciuria type I. About 30-40%, and possibly as many as 50%, of patients with absorptive hypercalciuria demonstrate abnormally elevated vitamin D-3 levels.
It has been suggested that some patients have an exaggerated response to, affinity for, or sensitivity to normal levels of vitamin D and its metabolites. Activation of vitamin D-3 takes place in the proximal renal convoluted tubule. This activation can be reduced by ketoconazole therapy.
Serum vitamin-D determinations can be helpful in determining the etiology of hypercalciuria in difficult or resistant cases, but these tests are probably are unnecessary in most hypercalciuric patients except as part of a research study or other standardized protocol.
Sarcoidosis and hypervitaminosis D
Sarcoidosis is a chronic disease that causes granulomas in various parts of the body but most often in the lungs. Although the exact cause is unknown, this condition is thought to arise from an exaggerated cellular immune response. The prevalence in the United States is about 1-4 cases per 10,000 population.
In some patients with sarcoidosis, 1,25-dihydroxyvitamin D is synthesized in an uncontrolled fashion by macrophages in the sarcoid granulomas. This produces a hypervitaminosis-D state with hypercalcemia and, frequently, hypercalciuria. Rarely, hypercalciuria is found without the hypercalcemia. This vitamin-D overproduction is not controlled by increased serum calcium, PTH, or phosphate administration.
Limiting sunlight exposure and reducing vitamin D ingestion are recommended. Glucocorticoid administration usually controls the hypercalcemia and hypercalciuria. Primary hyperparathyroidism has been reported in some patients with sarcoidosis. 
More than 30 million Americans experience kidney stone disease, with 1.2 million new cases each year. The percentage of people with hypercalciuria has been estimated to be at least 1 in 3 among people who form kidney stones, although some investigators have suggested that hypercalciuria can be found in as many as 60% of all calcium-stone formers. It is the most common metabolic abnormality found with calcium nephrolithiasis.
Despite a higher incidence of stone disease in the "stone belt," which is primarily the southeast portion of the United States, no clear biochemical difference was found when risk factors were compared among various regions of the country. Although nutritional and environmental influences would be expected to produce some variability, stone formers in all of the regions tested showed a striking similarity in urinary chemical risk factor profiles, with no significant biochemical differences noted that could be attributable to geographic factors.
Globally, the overall risk of forming stones differs in various regions. The probability is 1-5% in Asia, 5-9% in Europe, 13% in North America, and 20% in Saudi Arabia. Upper-tract stone disease is associated with an affluent lifestyle in developed countries where diets are high in animal protein, whereas bladder stones are predominant in developing countries and are related to poor socioeconomic conditions.
White persons tend to have stones more often than do black individuals. Whether this is due to genetic differences or is secondary to dietary and socioeconomic factors is unclear, although the latter explanation is suggested by the increasing incidence of nephrolithiasis in the nonwhite population.
A study by Whalley and associates from Johannesburg, South Africa, found that black male stone formers had similar chemistry profiles to those of the white male stone formers, although the risk factors were generally less severe.  The investigators compared lithogenic risk factors in healthy black male volunteers, black males who were recurrent stone formers, and white male recurrent stone formers. The subjects were observed over a 10-year period and were assessed with a thorough history, dietary analysis, and serum and urinary chemistry evaluation. No significant family history of stone disease was present in the black population studied, which suggests that genetic factors may be of more importance in the etiology of stone formation among whites. 
Similar findings were reported by Maloney and associates, who found that all racial groups tested (white, black, Asian, Hispanic) demonstrated remarkable similarity in the incidence of underlying metabolic abnormalities. 
A study by Rodgers and Lewandowski found that a low-calcium diet caused a statistically significant increase in urinary oxalate in black subjects but not in white subjects.  The results of a high-oxalate diet also differed between the black and white groups. 
The reference range of urinary calcium excretion for men generally is 275 mg or less per day, whereas in women the usual daily limit is only 250 mg. These reference values were created using large numbers of people (not calcium kidney-stone formers) to establish a reference range. The most likely reason for the discrepancy is that men are generally larger physically than women and have a correspondingly larger amount of material, such as calcium and uric acid, to excrete.
Clearly, stone development occurs when the chemical conditions are favorable, regardless of what any arbitrary reference range might be. For most practical purposes, the 250-mg/day limit for 24-hour urinary calcium excretion or a concentration of no more than 200 mg of calcium/liter of urine is used regardless of sex when the relative severity of hypercalciuria and overall risk of calcium kidney stone production are considered (see Table 1).
Postmenopausal women are more likely than men to demonstrate hypercalciuria. Hyperparathyroidism, which produces hypercalciuria, is more common in older women, and, because of concerns about their risk for osteoporosis, calcium supplementation is more popular with women.
In a study, women who developed calcium kidney stones had an average calcium intake that was 250 mg/day less than that of non–stone-forming women. This finding agrees with other studies that suggest that calcium stone formers should not restrict their calcium intake too aggressively.
When urinary chemistry and stone formation rate data were analyzed with the demographic information from a large national database of kidney stone formers, investigators found that obesity is a risk factor for kidney stone disease in women but not in men.
This finding is similar to that found in 2 large studies involving 81,000 women in the Nurses' Health Study and 51,000 men in the Health Professionals Follow-up Study. Investigators at Harvard who conducted these studies found that body size was a positive risk factor for kidney stone disease in women, but the correlation was much less significant in men.  The reason for this finding is unclear, but it may be related to estrogen levels. Whether this increased risk in women disappears when the excess body weight is lost is also unclear.
High-dose vitamin B-6 appears to be beneficial in women with calcium oxalate stone disease but probably not in men. Using data from more than 85,000 women with no history of kidney stones whose cases were monitored for 14 years, investigators found that those who took large amounts of vitamin B-6 had a significantly lower incidence of new calcium oxalate stone formation. A similar benefit of reduced calcium stone production from increased vitamin B-6 intake was not evident in an equivalent male study group. Similarly, carbohydrate intake was found to be a kidney stone dietary risk factor for women but not for men. (Incidentally, these studies found no benefit to dietary vitamin-C modifications in either men or women.)
As previously mentioned, pregnancy has long been thought to increase the incidence of urinary stones and hypercalciuria. Healthy, non–stone-producing pregnant women have been found to have hypercalciuria during all 3 trimesters.
The peak age range for calcium kidney stone production is generally 35-45 years. Another peak incidence of hypercalciuria occurs in postmenopausal women. In this older age group, many women are taking supplemental calcium for osteoporosis prophylaxis or therapy. The excess absorbed calcium eventually is released into the urine. In addition, postmenopausal women are at an increased risk of hyperparathyroidism, which can cause hypercalciuria.
Geriatric stone disease is relatively uncommon. The risk for newly formed stones in patients older than 65 years is quite low, although once a stone has formed the number and types of risk factors, as well as the risk of recurrent stones, are similar to those for younger stone formers. In particular, the incidence of hyperparathyroidism is higher in older persons and should be considered whenever an older patient presents with a first calcium kidney stone, particularly if the patient is female.
Hypercalciuria can occur at any age, including in newborns. The peak incidence of idiopathic hypercalciuria in children occurs at age 4-8 years.
The morbidity of hypercalciuria is related to 2 separate factors; ie, kidney stone disease and bone demineralization leading to osteopenia and osteoporosis.
Kidney stones are extremely painful because of the stretching, dilating, and spasm of the ureter and kidney caused by the acute obstruction. The pain is unrelated to the size of the stone or its composition and is related only to the rapidity and degree of the obstruction. Although normally functioning kidneys are quite resistant to damage from acute obstruction, aggressive surgical treatment is necessary in certain situations, such as a solitary kidney, renal transplantation, pyonephrosis (infection proximal to the obstruction), and intractable pain not relieved by parenteral analgesics.
Hypercalciuric stone formers have been demonstrated to have a lower average bone mineral density than non–stone formers matched for age and sex. Moreover, compared with normocalciuric stone formers, hypercalciuric patients have an average bone density that is 5-15% lower.  (In children with idiopathic hypercalciuria, bone mineral ̶ density measurements have consistently demonstrated Z-score reductions at the lumbar spine and, to a lesser extent, the femoral neck.  )
Bone loss is worsened if patients are placed on a calcium-restricted diet, as 99% of the body's calcium is stored in the bones. Fortunately, significant clinical bone loss is relatively rare. However, female hypercalciuric stone formers who become menopausal are at significantly greater risk of osteoporosis than their healthy female counterparts. The higher the urinary calcium excretion is, the greater the risk.
Untreated patients with an obligatory urinary calcium loss relatively unaffected by diet, as in renal leak hypercalciuria, renal phosphate leak, and resorptive hypercalciuria, develop a negative calcium balance that can result in osteopenia or osteoporosis.
Some patients may have a primary altered bone metabolism, as occurs in postmenopausal women with an estrogen deficiency. Thirty percent of hypercalciuric children already show evidence of bone loss, which suggests a metabolic disorder is responsible. Strong evidence exists suggesting that the underlying disorder causing the hypercalciuria is responsible for the bone demineralization, but other factors, such as an overly zealous dietary calcium restriction, undoubtedly play a role.
Patient education is extremely important in the treatment of hypercalciuria. Only a very motivated patient with an understanding of the need for continuing treatment can be expected to maintain any long-term preventive program, which typically lasts years.
Additionally, no immediate penalty exists for cheating, such as occurs in a patient with diabetes who forgets to take his/her morning insulin. In a hypercalciuric patient who fails to follow the treatment regimen, the penalty (the next kidney stone) may not become apparent for many months or even years. This means that only a truly motivated and informed patient can be expected to follow any therapeutic program for hypercalciuria on a long-term basis.
Two excellent sources of general patient information on kidney stones and hypercalciuria include PK Pietrow and ME Karellas’s " Medical Management of Common Urinary Calculi," available free online from American Family Physician, and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK).
For patients who desire more complete information, the National Institutes of Health (NIH) recommends The Kidney Stones Handbook, by GR Savtiz and SW Leslie, published by Four Geez Press.  This book includes a clearly written chapter on hypercalciuria, as well as many other aspects of kidney stone disease that would be of great interest to patients with nephrolithiasis and their families. It can be ordered by phone (1-800-2-KIDNEYS), online (http://www.kidneystonesbook.net/ ), or by writing directly to the publisher at the following address:
Four Geez Press
1911 Douglas Blvd
Roseville, CA 95661
What would you like to print?