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Hypercalciuria Treatment & Management

  • Author: Stephen W Leslie, MD, FACS; Chief Editor: Vecihi Batuman, MD, FACP, FASN  more...
Updated: Nov 26, 2015

Approach Considerations

Although optimal levels of urinary calcium have not been determined, less than 125 mg of calcium per liter of urine has been suggested as a reasonable optimal goal for most calcium-stone formers.

Dietary modifications have long been the mainstay of initial therapy for hypercalciuria. All hypercalciuric patients are advised to follow reasonable dietary changes to help limit their urinary calcium loss, reduce stone recurrences, and improve the effectiveness of medical therapy. Although dietary changes alone may not always be a successful or adequate treatment, dietary excesses possibly can undermine or defeat even optimal medical therapies.

On the other hand, patients who normalize their urinary calcium excretion with dietary changes alone may still benefit from thiazides or other therapies to avoid or treat bone demineralization and osteoporosis or osteopenia.[31]

Reducing intestinal calcium inadvertently may increase oxalate absorption and contribute to hyperoxaluria, resulting in a net increase in stone formation risk rather than a reduction. This is why dietary oxalate is limited whenever calcium intake is reduced.

Vitamin-D levels

As previously mentioned, many cases of absorptive hypercalciuria involve elevated vitamin-D levels.[8] Vitamin D increases small-bowel absorption of calcium and phosphate, enhances renal filtration, decreases parathyroid hormone (PTH) levels, and reduces renal tubular calcium absorption, which ultimately leads to hypercalciuria.

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.

Oral neutral phosphate therapy, limitation of vitamin-D and calcium intake, and reduction of sunlight exposure can also be useful in treating excess vitamin-D levels and hypervitaminosis D (usually caused by chronic ingestion of excessive amounts of vitamin D). Dipyridamole (Persantine) reduces renal phosphate excretion and may also be useful in controlling excessive vitamin-D levels and reducing vitamin D–dependent hypercalciuria.

Vitamin D is stored in fat, which means that in some cases vitamin-D intoxication may persist for weeks after vitamin-D ingestion has ceased. In these cases, glucocorticoids (roughly 100 mg of hydrocortisone per day or the equivalent) usually return calcium levels to normal within a few days.



Absorptive hypercalciuria type I

Treatment of absorptive hypercalciuria type I can be very difficult due to the severity of the intestinal calcium hyperabsorption. Therapy primarily consists of moderate dietary calcium restriction, thiazides, and orthophosphates.


Thiazides, such as trichlormethiazide (Naqua) or indapamide (Lozol), substantially reduce urinary calcium excretion, but they do not correct the primary defect, which is increased, uncontrolled intestinal calcium absorption. Thiazides may lose their hypocalciuric effect over time and cause hypokalemia, hypocitraturia, and increased uric acid levels.


Orthophosphates, such as K-Phos Neutral, Neutra-Phos K, and Uro-KP-Neutral, lower serum vitamin D-3 levels and reduce urinary calcium excretion. These agents are roughly equal to thiazides in their ability to reduce urinary calcium and prevent recurrent calcium stone formation. Because of the need for frequent dosing and various gastrointestinal adverse effects, orthophosphates are not the preferred agents when thiazides alone are sufficient and well tolerated. The combination of thiazides and orthophosphates used together may be necessary in difficult or resistant cases of absorptive hypercalciuria type I.

Sodium cellulose phosphate

Sodium cellulose phosphate is an extremely potent intestinal calcium-binding agent that was previously recommended as a primary therapy for absorptive hypercalciuria type I. Concerns about creating a negative calcium balance, bone demineralization, and other adverse effects currently limit its usefulness. These risks have shifted therapy away from this agent in favor of thiazides and orthophosphates.

When sodium cellulose phosphate therapy is used, supplemental magnesium is recommended. This is because the cellulose phosphate binds intestinal magnesium as well as calcium. Supplemental magnesium, therefore, must be administered to patients on cellulose phosphate to avoid magnesium depletion.


Dietary oxalate restriction is also recommended, due to the lack of free intestinal calcium that is created with cellulose phosphate therapy. This removes the primary intestinal oxalate-binding agent (calcium) from the digestive tract and leads directly to increased free intestinal oxalate absorption with subsequent hyperoxaluria.

Additional treatments

Other therapies include the use of increased dietary fiber, such as rice, oat, and wheat bran supplements, as relatively mild intestinal calcium binders. Bisphosphonates, such as alendronate (Fosamax), increase bone deposition of calcium, thus removing it from the circulation before it can be excreted. This improves bone calcium density and helps to reduce urinary calcium levels.

Optimization of all other urinary stone risk factors is highly recommended. This would include increasing urinary volume, reducing dietary oxalate, and using potassium citrate as needed. Purine intake should be restricted if uric acid levels are elevated.

Pentosan polysulphate (Elmiron) may potentially have use in difficult calcium oxalate stone cases. Although it has no effect specifically on calcium excretion, pentosan polysulphate appears to reduce calcium oxalate crystallization and crystal aggregation, which reduces new kidney stone formation rates.[32, 33, 34]

Absorptive hypercalciuria type II

Treatment is generally with dietary modifications, whenever possible, including restriction to a moderate calcium intake. Overly strict dietary calcium reductions are discouraged, however, because of the possibility of creating a negative calcium balance and osteoporosis. Moreover, dietary calcium reduction causes a lack of oxalate-binding sites in the intestinal tract, increasing urinary oxalate levels and potentially negating the benefit of urinary calcium reductions.

If patients decide that they cannot follow the recommended calcium diet or if the dietary changes are ineffective, orthophosphate and/or thiazide therapy is recommended. Some concern exists that when thiazides are used in these cases on a long-term basis, the hypocalciuric effect may become attenuated as the calcium stores in the bones become filled. If this problem occurs, it generally arises at least 2 years after treatment initiation. A period of alternate therapy, such as treatment with sodium cellulose phosphate or orthophosphates, can be used temporarily for approximately 6 months, and then the thiazides can be restarted.

No such problem exists with orthophosphate therapy, but current formulations need to be taken frequently and often have gastrointestinal adverse effects, such as diarrhea, bloating, and indigestion.

Absorptive hypercalciuria type III

Because the specific renal defect cannot be corrected in this condition, which is also known as renal phosphate leak hypercalcemia, the most effective treatment is oral orthophosphate therapy. This corrects the hypophosphatemia and limits the amount of vitamin D-3 activation that occurs.

The optimal orthophosphate supplement may be a slow-release neutral potassium phosphate (UroPhos-K), which has not yet been approved by the FDA. Dipyridamole (Persantine) also has been shown to increase the renal phosphate excretion threshold, which raises serum phosphate, normalizes high vitamin-D levels, and reduces hypercalciuria.[35]


Dietary Treatment

The following are recommendations in the dietary treatment of hypercalciuria:

  • Limit daily calcium intake to 600-800 mg/day unless otherwise instructed
  • 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)

Dietary modifications involving reasonable restrictions of dietary calcium, oxalate, meat (purines) and sodium, have been useful in reducing the urinary supersaturation of calcium oxalate. This effect is more pronounced in calcium oxalate ̶ stone formers with hypercalciuria than in calcium nephrolithiasis patients who are normocalciuric.

Some have suggested that the following 3 criteria need to be fulfilled for any dietary factor to be implicated in kidney stone disease:

  • Intake of the dietary constituent should be increased in patients with stones compared with controls
  • Restriction of the dietary factor should decrease stone formation rates
  • The reason the dietary factor causes stones needs to be understood

The main dietary contributions of calcium, sodium, potassium, animal protein, fiber, alcohol, caffeine, water, oxalate, and carbohydrates are reviewed individually below. No relationship between dietary fat and hypercalciuria has been found.

Calcium intake

Avoidance of an excessively high-calcium diet is an obvious recommendation for calcium-stone formers. (See the image below for a list of calcium-rich foods.) Stone formers as a group are much more sensitive to dietary calcium than non–stone formers. For any given change in dietary calcium, urinary calcium has been shown to increase an average of only 6% in healthy controls, but it can increase 20% in calcium-stone formers. Ingestion of more than 2000 mg of calcium per day generally results in hypercalciuria and/or hypercalcemia in calcium-stone formers.

Calcium-rich foods. Calcium-rich foods.

The recommended dietary calcium intake for most calcium-stone formers is about 600-800 mg/day. Avoiding a diet that is too severely limited in calcium is important, however, because otherwise a negative calcium balance may occur, with subsequent osteopenia or actual osteoporosis.

Moreover, when calcium is removed from the diet without also restricting oxalate intake, the lack of intestinal oxalate-binding sites may too much intestinal oxalate unbound and available for easy absorption. When this occurs, urinary oxalate levels rise. Proportionately, oxalate is 15 times stronger than calcium in promoting nephrolithiasis, so the net stone formation rate may actually increase if dietary oxalate intake and hyperoxaluria are not controlled. In 2 large population studies involving men and women, patients with the highest daily calcium intake were demonstrated to have significantly fewer stones (within reasonable limits) than did patients with the lowest dietary calcium levels.

Calcium citrate is recommended if calcium supplements are needed. This combination has been shown to be the most effective in limiting the new stone formation rate for those who require calcium supplements.

Any patient with kidney stones who is placed on a long-term, reduced calcium diet for any reason should have his/her bone density measured periodically, preferably in the spine. Urinary oxalate levels should also be checked regularly.

Pediatric patients

Children with hypercalciuria should be referred to a dietitian to accurately assess daily calcium, animal protein, and sodium intake. A trial low-calcium diet can be administered transiently to determine if exogenous calcium intake is contributing to the high urinary calcium. However, great caution should be used when trying to restrict calcium intake for long periods.

Because of concerns regarding poor bone matrix calcification and subsequent osteoporosis, no child should receive less than the daily recommended intake (DRI) of calcium for long periods without careful monitoring. If the dietary calcium is restricted to less than the DRI, bone density measurements and growth parameters should be taken at regular intervals to monitor the development of osteoporosis and growth retardation.

Reducing sodium and animal protein to the DRI may facilitate lowering of urinary calcium. However, the authors recommend that great caution be used when placing any child on a diet with less than the DRI of calcium and that a dietitian be consulted for assistance. If dietary changes do not provide the desired results of symptom relief, prevention of nephrolithiasis, and normalization of calcium excretion (< 4 mg/kg/day), pharmacotherapy should be initiated.

Sodium intake

A high sodium intake promotes various effects that enhance urinary calcium excretion and increase overall kidney stone formation rates. These effects include a rise in urinary pH, as well as in urinary calcium and cystine levels, and a decrease in urinary citrate excretion. Sodium and calcium share common sites for reabsorption in the renal tubules.

Urinary calcium levels

In healthy adults, high sodium intake has been associated with increased fractional intestinal calcium absorption and a rise in PTH and vitamin D-3 levels. Each 100-mEq increase in daily dietary sodium raises the urinary calcium level by about 50 mg.

Enhanced renal calcium excretion from high dietary sodium consumption is thought result from an increase in extracellular fluid volume, which ultimately results in inhibition of renal tubular calcium reabsorption.

Sodium intake among stone formers has been found to be equal to or higher than the intake in control groups of non–stone formers. Moreover, patients with recurrent nephrolithiasis and hypercalciuria have been found to be particularly sensitive to the hypercalciuric actions of a high-sodium diet.

Urinary pH levels

The rise in urinary pH is caused by an increase in serum and urinary bicarbonate levels. High serum bicarbonate lowers urinary citrate excretion by a direct effect on citrate metabolism in proximal renal tubular cells.

Dietary sodium reduction

Dietary sodium reduction has been shown to decrease urinary calcium excretion in stone formers with hypercalciuria, whereas high dietary sodium is associated with increased urinary calcium excretion and low bone density. (In postmenopausal women, high sodium intake has been directly associated with low bone density in calcium-stone formers.)

Patients should be aware that most restaurant meals and fast food items, such as pizza, contain a considerable amount of sodium. In addition, ketchup, mustard, teriyaki sauce, Worcestershire sauce, soy sauce, canned soups, cold cuts, prepared vegetables, and TV dinners have large amounts of sodium. However, many prepared foods have low-sodium varieties available.

Daily dietary salt intake should be restricted to levels sufficient to keep the urinary sodium excretion below 150-200 mEq/day. Most experts recommend limiting dietary sodium (salt) in calcium-stone formers to about 100 mEq/day, but this is difficult because many people find that salt enhances the taste of food. In children, a good target range for dietary sodium intake is 2-3 mEq/kg/day.

Recommendations to reduce sodium (salt) intake include the following:

  • Remove the saltshaker from the dining table; other spices, such as pepper, salt substitutes, or Mrs. Dash, can be used instead
  • Use little or no salt in food preparation or cooking
  • Avoid eating foods with high salt content whenever possible; most fast food is high in sodium.
  • Do not add any additional salt to foods that already contain it; this would apply to most prepared or canned foods, such as soups, gravies, TV dinners, and canned vegetables
  • Use fresh or frozen vegetables whenever possible; to reduce the salt content of canned vegetables, they should be drained and then rinsed with water before cooking
  • Use one half or less of the specified amount of salt when following cooking recipes
  • Everyone in the family should participate in the low-sodium diet so that the patient does not feel singled out

Dietary sodium needs to be controlled during any calcium testing, such as a calcium-loading test, to avoid affecting the results.

Potassium intake

Some evidence suggests that low potassium intake may be a risk factor for stones, but this has not been confirmed in all studies.[36, 37, 38] The potential influence of a low-potassium diet may be due to its relationship to sodium intake in stone formers, who generally have a higher sodium/potassium ratio than do non–stone formers.

Potassium decreases urinary calcium excretion by inducing transient sodium diuresis, which results in a temporary contraction of the extracellular fluid volume and an increase in renal tubular calcium reabsorption. Potassium also increases renal phosphate absorption, raising serum phosphate levels, which reduces serum vitamin D-3, resulting in decreased intestinal calcium absorption.

Animal protein intake

High protein intake has been judged second only to vitamin D ingestion in its ability to increase intestinal calcium absorption. Other effects of a high animal protein diet include an increase in urinary oxalate and uric acid, as well as a reduction in urinary citrate.

Urinary sulfate levels can be used as a general marker of oral animal protein intake. Generally, up to 40 mg of sulfate per day is considered normal, whereas in calcium-stone formers, optimal levels would be below 25-30 mg daily.

The possible link between high animal protein intake and kidney stones has been known since at least 1973. This link was found in epidemiologic studies first in India and then in England, Germany, Austria, Japan, Italy, and, finally, the United States.[39] Known stone formers appear to be more sensitive to the stone-enhancing effects of high–animal protein diets than do non–stone forming control populations.

Animal protein affects urinary calcium mainly through its acid-loading ability. Animal protein is high in purines, which are metabolized to uric acid, contributing to the acid load. Animal protein also increases the body's acid load directly. Methionine and cystine, which contain relatively high levels of sulfur, are more common in animal protein than plant protein. When the sulfur is oxidized to sulfate, additional acid is generated. (Sulfate also can form a soluble complex with calcium in the renal tubules, reducing calcium reabsorption and contributing to hypercalciuria.)

Excess acid needs to be neutralized. This often occurs in the bone, where the extra acid is buffered, releasing calcium from the bony stores. The released calcium eventually contributes to increased urinary calcium. Moreover, acid loading directly inhibits calcium reabsorption in the distal renal tubule, which further exacerbates any hypercalciuria. The extra acid also reduces urinary citrate excretion, by enhancing citrate reabsorption in the proximal renal tubule.

Dietary animal protein reduction

Each 75 g of additional dietary animal protein raises the urinary calcium level by 100 mg/day. In one study, increasing methionine ingestion by just 6 g/day was found to raise the daily urinary calcium excretion by 80 mg. Dietary animal protein intake should be less than 1.7 g/kg of body weight per day.

An intriguing randomized study that compared the stone production rates in about 100 known calcium oxalate stone formers who differed in their dietary protein and fiber intakes found significantly fewer stones in the group with the high-fiber, low–animal protein diet.[40] Of course, the possibility exists that the fiber or just the combination of the high fiber and animal protein restriction was effective.

The first group in the study was instructed just to increase fluid intake, whereas the second group was told to increase fluid intake and consume a high-fiber, low–animal protein diet; both groups were observed for 4.5 years.[40] Additional studies are needed to determine exactly which dietary modifications are most efficacious and to eliminate variables, such as uncontrolled sodium and calcium intake, that might influence the outcome.

Oxalate excretion

An association may also exist between high animal protein ingestion and increased oxalate excretion. For example, the production of glycolate, an oxalate precursor, is strongly linked to animal protein intake. However, although some investigators have found a link between high animal protein intake and increased urinary oxalate, others have not. Further studies are needed to determine the presence and significance of any such correlation.

Fiber intake

Calcium-stone formers as a group have a lower intake of dietary fiber than do healthy control populations. Dietary fiber, including oat, wheat, and rice bran, can reduce hypercalciuria and lower intestinal calcium absorption by 20-33%. As much as 24 g of dietary fiber per day may be necessary. Wheat bran, for example, is rich in oxalate, which accounts in part for its ability to bind and absorb free intestinal calcium.

However, although no significant adverse effects from increased dietary fiber have been reported, some potential risks exist. For example, dietary fiber may reduce intestinal magnesium, resulting in a deficit. Patients on a very high-fiber diet should be checked periodically for magnesium deficiency. A magnesium supplement, such as magnesium oxide, can be added if necessary.

Another potential problem is reactive enteric hyperoxaluria. Whenever intestinal calcium is reduced, fewer intestinal oxalate-binding sites are available. This leads to more free intestinal oxalate, which is absorbed more easily than oxalate bound to calcium or other agents. The increased free intestinal oxalate is absorbed and is eventually excreted in the urine, increasing urinary oxalate levels.

Because oxalate is proportionately about 15 times stronger than calcium with regard to stone promotion, limiting oxalate absorption in known stone formers makes sense. The easiest way to accomplish this is to limit dietary oxalate any time that intestinal oxalate-binding sites are reduced (such as when dietary calcium intake is reduced). Dietary oxalate can be lowered by limiting such foods as iced tea, coffee, colas, collard greens, spinach, chocolate, nuts, rhubarb, and green, leafy vegetables. Another approach is to use an alternate oxalate-binding agent, such as an iron supplement.

Alcohol intake

Acute alcohol ingestion causes hypoparathyroidism with hypercalciuria and hypocalcemia. PTH levels can drop by 70% after acute alcohol intoxication. Prolonged, moderate alcohol intake, however, eventually raises PTH levels. People with chronic alcoholism develop low serum vitamin D levels, which cause impaired intestinal calcium absorption and hypocalciuria.

A direct inhibitory effect on osteoblast activity by alcohol ingestion also appears to exist. This effect is enhanced in smokers. Urinary calcium excretion during periods of alcohol consumption can increase by more than 200% over control subjects. Osteopenia has also been linked to alcohol consumption.

Caffeine intake

Caffeine has been shown to increase urinary calcium excretion, but the clinical importance is relatively small unless very large amounts of caffeine are ingested. Ingestion of 34 ounces of caffeine is necessary to cause the loss of 1.6 mmol of total calcium. This caffeine-induced hypercalciuria seems to parallel changes in urinary prostaglandin F2-alpha (PGF2-alpha), which suggests that prostaglandins may play a role in hypercalciuria.

Fluid intake

Several studies have shown that on average, stone formers have a lower overall fluid intake than do non–stone formers. Not surprisingly, the highest incidence of kidney stone formation was in the group with the lowest overall fluid intake.

The need for a high fluid intake to increase urinary fluid volume seems obvious, because extra water decreases urinary concentration and reduces the likelihood of stones, even if the total calcium excretion is unchanged. The amount of extra water to be consumed is variable. In general, the author suggests an amount of water that produces a 24-hour urinary volume of 2000 mL or more. This amount may need to be increased in selected cases.

Citrus intake

Potassium-rich citrus fruits and juices, such as oranges, grapefruit, and cranberries, are recommended. Orange juice, for example, has natural potassium citrate. Lemon juice also has a very high citrate content, so lemonade made from real lemon juice is recommended. In contrast, lime juice contains mostly citric acid and does not increase urinary citrate substantially.

Oxalate intake

Oxalate is an organic acid found primarily in the leaves, bark, and fruit of plants. Its only known function in plants is to bind tightly with calcium. This is useful because it allows the plant to extract unwanted calcium from the internal circulation. The leaves containing the calcium-oxalate complex then can be discarded or shed by the plant. Humans absorb oxalate when oxalate-containing leaves and other vegetable products are eaten. Oxalate has no known useful function in human nutrition.

A relatively mild restriction of foods that contain high amounts of oxalate enables the body to avoid a reactive hyperoxaluria when intestinal oxalate-binding sites are reduced from a drop in oral calcium intake. Common foods with relatively high oxalate content include nuts, chocolate, colas, vegetables, rhubarb, spinach, collard greens, tea, and green, leafy vegetables.

Refined carbohydrate intake

Several large population studies have investigated the issue of the potential contribution of a high-carbohydrate diet to stone production. For example, Curhan found that carbohydrates were not a significant risk factor for stone formation in men but that they were associated with increased stone production in women. Some investigators found that stone formers tend to have a higher carbohydrate intake than non ̶ stone formers, but other researchers have failed to confirm this association.

Good evidence indicates that a high-carbohydrate diet causes an increase in urinary calcium excretion because of decreased distal renal tubular calcium reabsorption and an increase in intestinal calcium absorption. There is also evidence to indicate that excessive carbohydrate loading can increase endogenous oxalate production. This seems reasonable, because glucose is involved in oxalate metabolism through a series of chemical interactions with glyoxylate. (Glyoxylate is involved not only in the metabolism of endogenous oxalate but also in the gluconeogenesis pathway and urea metabolism.)

Ketogenic diet

The ketogenic diet is sometimes used to treat intractable seizure disorders in children. It involves an initial period of fluid restriction and starvation until ketone bodies appear in the urine. This is followed by a low-protein, low-carbohydrate, fluid-restricted diet, which tends to cause chronic metabolic acidosis with hypocitraturia and relatively low urinary volumes, which, in turn, induce kidney stone formation. Elevated uric acid levels have also been reported.

The average time from initiation of the diet until stone presentation is about 18 months, so patients who are started on this diet should be checked for stone formation at about 12 months after diet application. Fluid liberalization and citrate supplements can be used to prevent kidney stone formation in these patients.


Pharmacologic Therapy

Medical therapy is used to treat hypercalciuria whenever dietary treatment alone is inadequate, ineffective, unsustainable, or intolerable for the patient.[5] Generally, medical therapy should be used together with dietary treatment for optimal results and health.

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

Combination therapy with multiple medicines is possible and recommended in unusual or difficult cases.[41] Occasionally, ketoconazole and dipyridamole are useful in lowering vitamin-D levels in selected patients.

Pharmacological therapy in children

Dietary modification alone may not be enough to improve bone mineral density in children with idiopathic hypercalciuria.[15] Children with idiopathic hypercalciuria may have improvement in the bone mineral density z-score after treatment with potassium citrate and thiazides.[16] Thus, the indication for starting medications is evidence of bone demineralization or history of previous renal stone formation. Hydrochlorothiazide (HCTZ) and other thiazide-type diuretics are the agents most frequently used to treat hypercalciuria.


Thiazides are currently the mainstay of medical therapy for hypercalciuria. These agents do not directly affect intestinal calcium absorption but instead stimulate calcium reabsorption in the distal renal tubule. In addition, thiazides decrease extracellular fluid volume and increase proximal renal tubular calcium reabsorption. They generally lower urinary calcium levels by about one third, but reductions of as much as 50% or 400 mg/day have been reported. (Their hypocalciuric effect is reduced, however, if sodium intake is not limited.)[42]

Even when used in a nonselective fashion, thiazides can reduce stone recurrences from 50% (untreated) to 20% (treated) over 5 years. Thiazides are particularly well suited for hypercalciuric patients with hypertension, especially when dietary control measures alone fail to adequately normalize urinary calcium excretion.

Renal leak hypercalciuria

Thiazides are specifically indicated for renal leak hypercalciuria, in which case they not only reduce the inappropriate renal calcium loss but also lower PTH levels and correct other metabolic problems. When used appropriately in renal leak hypercalciuria, thiazides prevent secondary hyperparathyroidism and normalize vitamin D-3 synthesis, calcium absorption, and urinary calcium excretion. Stone formation rates drop more than 90% in patients with renal calcium leak who are placed on long-term thiazide therapy.

Absorptive hypercalciuria

When used for absorptive hypercalciuria, thiazides are still effective, but their long-term usefulness may diminish over time as the bone stores become filled, allowing the hypercalciuria to return. Until then, bone density on thiazide therapy has been shown to increase by about 1.5% or more per year. When thiazides lose their hypocalciuric effect, which has been reported to occur, on average, about 2 years after therapy initiation, the use of an alternate regimen for a period of approximately 6 months usually restores the efficacy of the thiazide medication for use in hypercalciuria.

Other thiazide effects

Thiazides have many other effects on the body. These drugs increase serum calcium and uric acid levels while decreasing urinary citrate levels. Hyperuricemia and acute gout rarely develop in individuals receiving thiazides.

However, adverse effects occur in about one third of patients, although they are usually mild. For example, a risk of hypokalemia, hyponatremia, hypocitraturia, and magnesium loss, as well as of cholesterol level increase, exists. Moreover, thiazides tend to increase urinary volume because of their diuretic effect, a useful feature in kidney stone formers but one that can also easily lead to dehydration if oral fluid intake is not maintained.

The most bothersome clinical adverse effect is lethargy, but muscle aches, depression, decreased libido, generalized weakness, and malaise also can occur. About 20% of patients stop thiazide therapy because of these adverse effects.

Chemically, thiazides are sulfonamides and generally should not be used or should be used cautiously in patients with a history of sulfa allergy. Drug interactions have been reported when thiazides are used together with alcohol, barbiturates, narcotics, antidiabetic drugs, steroids, pressor amines, muscle relaxants, lithium, and nonsteroidal anti-inflammatory agents (NSAIDs).

Most patients on thiazides do not need any potassium supplementation, but potassium and electrolyte levels need to be checked periodically. Because of the risk of hypokalemia and hypocitraturia, potassium citrate supplements are often prescribed along with thiazides in calcium-stone formers.

Thiazide dosing

Thiazide dosage depends on the specific medication used. Once-a-day drug preparations are usually preferred because of better patient compliance and tolerability. Trichlormethiazide (Naqua) is administered as a 2- or 4-mg daily tablet. Indapamide (Lozol) can be administered in either 1.25- or 2.5-mg doses once a day.

If a potassium-sparing combination is desired, those that contain triamterene, such as Dyazide, should be avoided, because triamterene can form its own stones. Moduretic, which uses amiloride as a potassium-sparing diuretic, would be recommended. Amiloride does not form stones and has a mild hypocalciuric effect of its own.


In 1962, Howard et al first suggested the use of orthophosphate therapy (K-Phos Neutral, Neutra-Phos K, Uro-KP-Neutral) as a preventive treatment for kidney stones.[43] Stone cessation rates of more than 90% have been reported with this agent.

Orthophosphate therapy has been shown to decrease urinary calcium excretion by lowering serum vitamin D-3 levels (which reduces intestinal calcium absorption) and by increasing renal tubular calcium reabsorption. Orthophosphates may also have some intestinal calcium-binding capability, but the limited studies conducted on this issue have not confirmed this effect.

Overall, orthophosphates lower 24-hour urinary calcium excretion by about 50% in patents with absorptive hypercalciuria and by about 25% in patients with other hypercalciuric states. No apparent effect on PTH levels exists in healthy individuals. Uncontrolled studies have shown kidney stone remission rates of 75-91% in recurrent stone formers on long-term orthophosphate therapy.

Orthophosphates also increase urinary stone inhibitors such as citrate and, particularly, pyrophosphate. Many patients (40% in one series) have even noted a loss of stone mass while on orthophosphate therapy. Orthophosphates are particularly useful in cases of absorptive hypercalciuria type III (renal phosphate leak) and when thiazides cannot be used or are ineffective.

The use of orthophosphates with thiazides is extremely effective in controlling urinary calcium excretion and reducing new kidney stone formation rates, particularly in hypercalciuric calcium oxalate stone formers.

About 60% of all dietary phosphate is absorbed in the duodenum and jejunum; 65% percent of the absorbed phosphate is excreted by the kidneys, and the rest is eliminated through the intestinal tract by secretion in the ileum and colon.

Adverse effects of orthophosphates

Side effects of orthophosphate therapy include diarrhea, bloating, and gastrointestinal upset. These usually are worst during the first 2 weeks of therapy, after which they tend to diminish. The medication must be taken 3-4 times per day, which reduces patient compliance.

Do not administer to patients with struvite (magnesium ammonium phosphate) stones or to patients with renal failure, because they can develop soft-tissue calcifications. Use cautiously in patients with a history of predominantly calcium phosphate stones or in whom the urinary pH is consistently alkaline (which promotes calcium phosphate precipitation and stone formation). In addition, patients with a previous history of gastrointestinal problems generally do not tolerate orthophosphate therapy well.

Currently available orthophosphate preparations tend to be rapidly dissolving, which increases the gastrointestinal upset and diarrhea. A slow-release form of potassium phosphate (UroPhos-K) is currently awaiting United States Food and Drug Administration (FDA) approval. This new preparation uses a wax matrix to slow the release of phosphate, reducing its adverse effects. It contains no sodium and is designed to modify urinary pH to 7.0, which discourages the formation of calcium phosphate crystals and calculi.

In a randomized, double-blind study, patients with absorptive hypercalciuria type I who were administered the slow-release phosphate preparation had an average daily urinary calcium level of only 171 mg; controls averaged levels of 288 mg/day.[44] Urinary inhibitor levels of citrate and pyrophosphate were increased in the group treated with orthophosphate, and no gastrointestinal adverse effects were reported.[44]

Orthophosphate dosing

To be effective, orthophosphates must be taken at regular intervals and in sufficient amounts. The neutral salt tends to have fewer adverse effects and is more effective than other preparations. Optimal levels of neutral orthophosphate are 1-2.5 g/day. Orthophosphate preparations for calcium-stone formers should be sodium free.


Bisphosphonates such as alendronate (Fosamax), risedronate (Actonel), and ibandronate (Boniva) have become useful in the treatment of hypercalciuria and hypercalcemia. These agents are particularly helpful in cases of hyperparathyroidism in which parathyroid surgery cannot be performed or medical therapy is desired.

Bisphosphonates are analogues of pyrophosphate with a high affinity for the hydroxyapatite of bone, especially in areas of rapid turnover and bone resorption. These drugs inhibit osteoclast activity, which causes a net increase in bone density, calcium deposition, and mineralization. Preferential binding to osteoclasts is roughly 10 times greater than osteoblastic binding.

Although bisphosphonates are clearly helpful in cases of overt hypercalcemia and hyperparathyroidism, their usefulness in the long-term treatment of hypercalciuria in recurrent stone formers is unproved. These agents may be most useful in hypercalciuric stone formers in whom a history of decreased bone density or other evidence of osteoporosis, such as elevated osteocalcin levels, is present. Combination therapy with thiazides would be expected to be particularly beneficial. Bisphosphonates can also be helpful in difficult cases of hypercalciuria when other measures are unsuccessful or poorly tolerated.

Bisphosphonate with thiazide

In a study of 70 patients with recurrent lithiasis, hypercalciuria, and bone-density loss, Arrabal-Polo et al found that after 2 years of treatment the patients receiving a combination of bisphosphonate and thiazide had a significantly greater decrease in calciuria and improvement in bone density than did patients treated with bisphosphonate alone. Half of the patients in the study were treated with 70 mg/wk of alendronate, while the other 35 patients were treated with a combination of 70 mg/wk of alendronate and 50 mg/day of hydrochlorothiazide.[31]

Sodium cellulose phosphate

Sodium cellulose phosphate (Calcibind) is an extremely effective intestinal calcium-binding agent. This agent removes about 85% of the available intestinal calcium from the digestive tract and prevents its absorption. Sodium cellulose phosphate is about 11% sodium and has a calcium-binding capacity of 1.8 mmol of calcium per gram of cellulose phosphate. In the digestive tract, the sodium ion is exchanged for calcium, which is then excreted bound to the cellulose in the stool.

When sodium cellulose phosphate is used as a therapy, supplemental magnesium and dietary oxalate restriction are recommended, because the cellulose phosphate binds magnesium as well as calcium and results in a magnesium deficiency if supplemental magnesium is not supplied.

The need for the dietary oxalate restriction (primarily of tea, cola, coffee, chocolate, nuts, and green, leafy vegetables) is due to the lack of available intestinal calcium that the cellulose therapy creates. With so much intestinal calcium bound to the cellulose, intestinal oxalate-binding sites are severely lacking. This leaves an excess of free, unbound intestinal oxalate available for absorption, which then increases oxaluria.

Unfortunately, sodium cellulose phosphate causes a reduction in absorbed calcium, which makes it useful against hypercalciuria but may cause a negative calcium balance and subsequent reduction in bone density.

The drug may nonetheless have a role in the diagnosis of hypercalciuria if used in a brief therapeutic trial and it may be useful in selected cases of absorptive hypercalciuria type I when other therapies are ineffective. The benefits of its use must be judged sufficient to justify the risks. Other treatments, such as thiazides and bisphosphonates, can be used to prevent unnecessary bone demineralization and limit the dosage of cellulose required, minimizing the adverse effects and complications associated with sodium cellulose phosphate.


Dipyridamole (Persantine) is a platelet adhesion inhibitor and vasodilator. It is usually used to lengthen platelet survival time and reduce the incidence of thromboembolic phenomenon after heart valve replacement surgery. Researchers have found that dipyridamole reduces renal phosphate excretion, which increases the serum phosphate level, resulting in decreased activation of vitamin D-3 and then in reduced hypercalciuria. This is useful in patients with vitamin D–dependent hypercalciuria, such as the renal phosphate leak (absorptive hypercalciuria type III) form, especially when orthophosphates are not tolerated or cannot be used.

No direct effect on urinary calcium excretion is present. Adverse effects are minimal, but the medication must be taken frequently. Dipyridamole has been shown to reduce urinary calcium excretion in patients with vitamin D–dependent renal phosphate leak on a long-term basis.[35, 45]

Parathyroid hormone

PTH or its amino-terminal fragment has been shown stimulate bone formation and resorption without causing hypercalcemia. Once-daily injections of PTH tend to maximize the osteoblastic activity while minimizing bone resorption for a net gain in bone mass. This treatment was tested in a large, multicenter trial of 9347 postmenopausal women with osteoporosis. All of the patients received vitamin D and calcium supplementation.[46]

The group that received the PTH injections had reductions in fracture rates of 65-86%.[46] Urinary calcium excretion was increased only slightly (roughly by 30 mg of calcium per day in the treated group), but the overall incidence of hypercalciuria was no different between the PTH-treated group and the patients who received placebo. This most likely was due to the single daily dosing of the PTH, which minimized the hypercalcemic and hypercalciuric responses.[46]

In short, this is a promising avenue of research for osteoporosis and osteopenia that appears to have no significant effect on hypercalciuria or calcium stone formation. Further research on this and other osteoblast-enhancing therapies holds promise in treating osteoporosis and, possibly, select cases of hypercalciuria.


Renal Leak Hypercalciuria Therapy

Treatment of renal leak hypercalciuria is primarily with thiazides. These medications specifically return calcium from the renal tubule to the serum, generally reduce urinary calcium levels by 30-40%, and eliminate secondary hyperparathyroidism. This hypocalciuric effect of thiazides is diminished or eliminated if dietary sodium is not restricted.

Adverse effects of thiazides include an increase in uric acid and a decrease in urinary citrate; they also can cause hypokalemia. To correct these potential problems, potassium citrate often is administered to patients on long-term thiazide therapy. When used appropriately in renal leak hypercalciuria, thiazides work extremely well and do not appear to attenuate their hypocalciuric effect over time. Chemically, thiazides are sulfonamides and should be used cautiously, if at all, in patients with a known sulfa allergy.

Preferred forms of thiazide therapy include trichlormethiazide (Naqua) 2-4 mg/day and indapamide (Lozol) 1.25-2.5 mg/day. These 2 medications can be administered just once a day and tend to carry fewer adverse effects than do shorter-acting thiazides. Potassium citrate is often added to the thiazide therapy to prevent hypokalemia and to increase urinary citrate levels. The dosage of potassium citrate should be adjusted based on serum potassium and 24-hour urinary citrate levels.


Resorptive Hypercalciuria and Hyperparathyroidism Therapy

The recommended treatment for patients with hyperparathyroidism who produce calcium stones is parathyroid surgery. For individuals who are unable or unwilling to undergo the surgery, medical treatment is available. Bisphosphonates are the medical agents of choice, because they correct the hypercalcemia, reduce bone resorption, and lower urinary calcium excretion. Orthophosphates and calcitonin can be used for these patients as well.

Thiazides should not be used in patients with hyperparathyroidism, even when hypercalciuria is present, because of the risk of increasing the hypercalcemia. (The only exception would be a short course for testing purposes in carefully selected patients, inducing a mild, controlled increase in serum calcium while monitoring the PTH level to see if it drops appropriately or is autonomous.)

Estrogens should be used in postmenopausal women with hypercalciuria whenever possible. Their action is similar to that of the bisphosphonates.

PTH actually stimulates osteoblastic and osteoclastic cells. High, sustained levels of PTH result in a net loss of calcium and bone mass, but research indicates that intermittent injections of PTH in animals and humans produce a net increase in osteoblastic activity and bone mass. This intermittent therapy, which appears promising as a potential treatment for osteoporosis, does not seem to significantly affect hypercalciuria or serum calcium levels.

Calcimimetic drugs

Calcimimetic agents, such as cinacalcet (Sensipar), are a new and exciting modality being studied for the medical treatment of hyperparathyroidism.[47, 48, 49, 50, 51] Activation of specific calcium receptors on parathyroid cells by these calcimimetic agents inhibits PTH secretion. Essentially, the drug increases the sensitivity of calcium-sensing receptors.

Therapy with calcimimetic agents has already been used successfully in hyperparathyroid patients, particularly in those with chronic renal failure who were on dialysis and had secondary hyperparathyroidism. A 50-60% decrease in circulating PTH and a mild decrease in serum calcium levels have been reported, but the hypercalciuria is not significantly affected. The agents may be also useful in resistant hypercalcemias and parathyroid cancers, as well as in the medical treatment of hyperparathyroidism.

Vitamin D

Paricalcitol is a vitamin-D analogue that was developed to help prevent and treat secondary hyperparathyroidism in patients with chronic renal failure. Actual vitamin D also suppresses parathyroid hormone levels but tends to cause hypercalcemia and hyperphosphatemia. Vitamin-D analogues such as paricalcitol are able to significantly reduce PTH levels without significantly changing serum levels or urinary excretion of either calcium or phosphorus.


Bone-Density Management

The issue of hypercalciuria treatment can be complicated by the presence of osteoporosis or osteopenia. A serum calcium determination is the first step in identifying patients with possible hyperparathyroidism. The identification of elevated serum calcium levels should be followed up with a simultaneous PTH level to diagnose hyperparathyroidism.

Even without a history of calcium kidney stones, a 24-hour urine test to check urinary calcium excretion can be useful in the management of osteoporosis. If the patient has hypercalciuria (and hyperparathyroidism has been eliminated by serum testing), the patient will benefit from thiazide therapy, which increases serum calcium and reduces excessive urinary calcium excretion.

Estrogen should be used, if appropriate, in postmenopausal women. Bisphosphonates, such as alendronate (Fosamax), risedronate (Actonel), or ibandronate (Boniva), should be used in men and in women when estrogen cannot be used.

Calcium supplementation can be helpful in osteoporosis, but urinary calcium levels need to be monitored carefully in calcium stone–forming patients, especially if they demonstrate overt hypercalciuria.

Studies have shown that, for most postmenopausal women with osteoporosis but with no previous history of calcium kidney stone disease, the overall risk of calcium nephrolithiasis does not increase significantly with the use of supplemental calcium or of combined calcium with calcitriol, despite an increase in urinary calcium excretion.[20]

Calcium citrate is recommended for calcium-stone formers in this situation, because its citrate component limits any increase in stone formation rate. Medical therapy, including thiazides, should be started first; calcium citrate can then be added until the urinary calcium level reaches the normal upper limit (250 mg of calcium per 24 hours or 4 mg of calcium per kilogram of body weight).

Other treatment for possible urinary stone risk factors, such as uric acid, citrate, volume, phosphate, sodium, magnesium, and oxalate, should be optimized.



The treatment of hypercalciuria is important not only in the reduction of future kidney stone formation and the diagnosis of possible underlying metabolic disease but also in the prevention of bone demineralization and osteoporosis.

Every physician who treats patients with hypercalciuria may not be able to become an expert on this condition or its therapy. Physicians who are uncomfortable treating such patients should not hesitate to refer them, especially if the patients are highly motivated and interested in treating their calcium problem. A difficult or high-risk case that is resistant to dietary and standard medical therapy in a motivated patient would be a good case to refer to a physician expert or tertiary care center with expertise in this area.

Patients with hyperparathyroidism should be referred to a physician skilled in dealing with this condition. Patients with overt renal failure need the assistance of a nephrologist.


Deterrence and Prevention

Every patient with at least 1 kidney stone should be offered the opportunity for stone prevention testing and prophylactic therapy. This is most critical in children and in patients with renal failure or a single functioning kidney. For most adult patients, this is optional, but testing and preventive treatment needs to be offered and the consequences of additional preventable stones reviewed.

Even if patients refuse preventive testing and prophylactic therapy, they should be advised of the potential risks of recurrent stones and be provided with general dietary advice regarding moderation of calcium, animal protein, sodium, purines, and oxalate ingestion. All patients with history of kidney stones need to increase their fluid intake. Patients with hypercalciuria must be cautioned about the risks of an overly severe reduction in oral calcium intake, which actually can increase their risk of new stone formation.

Osteocalcin monitoring

An intriguing suggestion has been made that osteocalcin levels be used before and after dietary calcium restriction.[52] Osteocalcin is released during periods of bone resorption, which would be expected with renal leak hypercalciuria, hyperparathyroidism, or any dietary calcium ̶ resistant hypercalciuria. Patients with elevated osteocalcin levels theoretically would benefit from thiazide and/or bisphosphonate therapy to prevent bone demineralization over time, even if their hypercalciuria is well controlled with dietary therapy alone. Estrogen can be added in women.


Long-Term Monitoring

Repeat 24-hour urine testing and appropriate blood determinations are needed until the patient’s hypercalciuria is controlled and stable. Once this occurs, repeat testing can be performed less often. Testing once per year is considered reasonable for patients whose stone production and level of hypercalciuria are controlled. If hypercalciuria is not well controlled, appropriate adjustments can be suggested and testing should be repeated more frequently.

As patients modify their diets, they may substitute new foods and beverages for the ones previously restricted. These new dietary items can have an unpredictable effect on the various stone risk factors. Therefore, follow-up 24-hour urine tests should include all of the major stone risk factors and not just calcium.

Routine radiographs, such as an abdominal flat plate (also called KUB [for kidneys, ureters, and bladder]) or plain renal tomograms, are useful for finding any newly formed stones. This is particularly important and helpful in patients whose hypercalciuria is poorly controlled.

Some patients pass additional stones and assume their treatment plan is not working when, actually, these stones had already formed before testing or treatment began. Establishing the number, size, and location of any existing calculi before testing or treatment begins is important. In this way, patients can be reassured that their treatment plan is successfully controlling their hypercalciuria.

Patients with hypercalciuria who have known osteopenia, osteoporosis, or bone demineralization and those with untreated or unresponsive hypercalciuria should have periodic bone density measurements, especially if they are aged 50 years or older.

Pediatric patients

Children with hypercalciuria should be followed at regular intervals by a pediatric nephrologist. Twenty-four–hour urine collections for calcium clearance should be monitored at 6-month intervals. Growth parameters should be followed in all children, and bone mineralization should be measured if less than the DRI of calcium is consumed. Serum electrolytes, uric acid, and lipid panels should be monitored in children on thiazide therapy.

Contributor Information and Disclosures

Stephen W Leslie, MD, FACS Founder and Medical Director, Lorain Kidney Stone Research Center; Associate Professor of Surgery, Creighton University School of Medicine, Chief of Urology, Creighton University Medical Center

Stephen W Leslie, MD, FACS is a member of the following medical societies: American College of Surgeons, American Urological Association, National Kidney Foundation, Ohio State Medical Association

Disclosure: Nothing to disclose.


Sahar Fathallah-Shaykh, MD Associate Professor of Pediatric Nephrology, University of Alabama at Birmingham School of Medicine; Consulting Staff, Division of Pediatric Nephrology, Medical Director of Pediatric Dialysis Unit, Children's of Alabama

Sahar Fathallah-Shaykh, MD is a member of the following medical societies: American Society of Nephrology, American Society of Pediatric Nephrology

Disclosure: Nothing to disclose.

Chief Editor

Vecihi Batuman, MD, FACP, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology

Disclosure: Nothing to disclose.


Sahar Fathallah-Shaykh, MD Assistant Professor in Pediatric Nephrology, University of Alabama at Birmingham School of Medicine; Consulting Staff, Division of Pediatric Nephrology, Medical Director of Pediatric Dialysis Unit, Children's of Alabama

Sahar Fathallah-Shaykh, MD is a member of the following medical societies: American Society of Nephrology and American Society of Pediatric Nephrology

Disclosure: Medscape Reference Honoraria Other

Frederick J Kaskel, MD, PhD Director of the Division and Training Program in Pediatric Nephrology, Vice Chair, Department of Pediatrics, Montefiore Medical Center and Albert Einstein School of Medicine

Frederick J Kaskel, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American Pediatric Society, American Physiological Society, American Society of Nephrology, American Society of Pediatric Nephrology, American Society of Transplantation, Eastern Society for Pediatric Research, Federation of American Societies for Experimental Biology, International Society of Nephrology, NationalKidneyFoundation, New York Academy of Sciences, Renal Physicians Association, Sigma Xi, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Craig B Langman, MD The Isaac A Abt, MD, Professor of Kidney Diseases, Northwestern University, The Feinberg School of Medicine; Division Head of Kidney Diseases, The Ann and Robert H Lurie Children's Hospital of Chicago

Craig B Langman, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Nephrology, and International Society of Nephrology

Disclosure: NIH Grant/research funds None; Raptor Pharmaceuticals, Inc Grant/research funds None; Alexion Pharmaceuticals, Inc. Grant/research funds None

Richard Neiberger, MD, PhD Director of Pediatric Renal Stone Disease Clinic, Associate Professor, Department of Pediatrics, Division of Nephrology, University of Florida College of Medicine and Shands Hospital

Richard Neiberger, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Federation for Medical Research, American Medical Association, American Society of Nephrology, American Society of Pediatric Nephrology, Christian Medical & Dental Society, Florida Medical Association, International Society for Peritoneal Dialysis, International Society of Nephrology, National Kidney Foundation, New York Academy of Sciences, Shock Society, Sigma Xi, Southern Medical Association, Southern Society for Pediatric Research, and Southwest Pediatric Nephrology Study Group

Disclosure: Nothing to disclose.

Deogracias Pena, MD Medical Director of Dialysis, Department of Pediatrics, Cook Children's Medical Center; Clinical Associate Professor, Texas Tech University Health Sciences Center

Deogracias Pena, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, and American Society of Pediatric Nephrology

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Martha K Terris, MD, FACS Professor, Department of Surgery, Section of Urology, Director, Urology Residency Training Program, Medical College of Georgia; Professor, Department of Physician Assistants, Medical College of Georgia School of Allied Health; Chief, Section of Urology, Augusta Veterans Affairs Medical Center

Martha K Terris, MD, FACS is a member of the following medical societies: American Cancer Society, American College of Surgeons, American Institute of Ultrasound in Medicine, American Society of Clinical Oncology, American Urological Association, Association of Women Surgeons, New York Academy of Sciences, Society of Government Service Urologists, Society of University Urologists, Society of Urology Chairpersons and Program Directors, and Society of Women in Urology

Disclosure: Nothing to disclose.

Taylor S Troischt, MD Clinical Assistant Professor of Pediatrics, West Virginia University Hospitals; Medical Director, Cheat Lake Physicians

Taylor S Troischt, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, and Phi Beta Kappa

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

  1. Moreira Guimarães Penido MG, de Sousa Tavares M, Campos Linhares M, Silva Barbosa AC, Cunha M. Longitudinal study of bone mineral density in children with idiopathic hypercalciuria. Pediatr Nephrol. 2012 Jan. 27(1):123-30. [Medline].

  2. Nacaroglu HT, Demircin G, Bülbül M, Erdogan O, Akyüz SG, Caltik A. The association between urinary tract infection and idiopathic hypercalciuria in children. Ren Fail. 2013. 35(3):327-32. [Medline].

  3. Madani A, Kermani N, Ataei N, Esfahani ST, Hajizadeh N, Khazaeipour Z, et al. Urinary calcium and uric acid excretion in children with vesicoureteral reflux. Pediatr Nephrol. 2012 Jan. 27(1):95-9. [Medline].

  4. Silverberg SJ, Lewiecki EM, Mosekilde L, Peacock M, Rubin MR. Presentation of asymptomatic primary hyperparathyroidism: proceedings of the third international workshop. J Clin Endocrinol Metab. 2009 Feb. 94(2):351-65. [Medline].

  5. Schwaderer AL, Srivastava T, Schueller L, Cronin R, Mahan JD, Hains D. Dietary modifications alone do not improve bone mineral density in children with idiopathic hypercalciuria. Clin Nephrol. 2011 Nov. 76(5):341-7. [Medline].

  6. Vezzoli G, Soldati L, Gambaro G. Update on primary hypercalciuria from a genetic perspective. J Urol. 2008 May. 179(5):1676-82. [Medline].

  7. Curhan GC, Willett WC, Speizer FE, Stampfer MJ. Twenty-four-hour urine chemistries and the risk of kidney stones among women and men. Kidney Int. 2001 Jun. 59(6):2290-8. [Medline].

  8. Zwart SR, Parsons H, Kimlin M, Innis SM, Locke JP, Smith SM. A 250 µg/week dose of vitamin D was as effective as a 50 µg/d dose in healthy adults, but a regimen of four weekly followed by monthly doses of 1250 µg raised the risk of hypercalciuria. Br J Nutr. 2013 Apr 18. 1-7. [Medline].

  9. Parks JH, Coe FL, Evan AP, Worcester EM. Clinical and laboratory characteristics of calcium stone-formers with and without primary hyperparathyroidism. BJU Int. 2009 Mar. 103(5):670-8. [Medline].

  10. Srivastava T, Alon US. Pathophysiology of hypercalciuria in children. Pediatr Nephrol. 2007 Oct. 22(10):1659-73. [Medline].

  11. Worcester EM, Coe FL. New insights into the pathogenesis of idiopathic hypercalciuria. Semin Nephrol. 2008 Mar. 28(2):120-32. [Medline]. [Full Text].

  12. Nesterova G, Malicdan MC, Yasuda K, Sakaki T, Vilboux T, Ciccone C, et al. 1,25-(OH)2D-24 Hydroxylase (CYP24A1) Deficiency as a Cause of Nephrolithiasis. Clin J Am Soc Nephrol. 2013 Apr. 8(4):649-57. [Medline]. [Full Text].

  13. Dimke H, Desai P, Borovac J, Lau A, Pan W, Alexander RT. Activation of the Ca(2+)-sensing receptor increases renal claudin-14 expression and urinary Ca(2+) excretion. Am J Physiol Renal Physiol. 2013 Mar 15. 304(6):F761-9. [Medline].

  14. Vezzoli G, Terranegra A, Soldati L. Calcium-sensing receptor gene polymorphisms in patients with calcium nephrolithiasis. Curr Opin Nephrol Hypertens. 2012 Jul. 21(4):355-61. [Medline].

  15. Pipili C, Oreopoulos DG. Vitamin d status in patients with recurrent kidney stones. Nephron Clin Pract. 2012. 122(3-4):134-8. [Medline].

  16. Park SY, Mun HC, Eom YS, Baek HL, Jung TS, Kim CH, et al. Identification and characterization of D410E, a novel mutation in the loop 3 domain of CASR, in autosomal dominant hypocalcemia and a therapeutic approach using a novel calcilytic, AXT914. Clin Endocrinol (Oxf). 2013 May. 78(5):687-93. [Medline].

  17. Luyckx VA, Leclercq B, Dowland LK, Yu AS. Diet-dependent hypercalciuria in transgenic mice with reduced CLC5 chloride channel expression. Proc Natl Acad Sci U S A. 1999 Oct 12. 96(21):12174-9. [Medline]. [Full Text].

  18. Duffey BG, Pedro RN, Kriedberg C, Weiland D, Melquist J, Ikramuddin S, et al. Lithogenic risk factors in the morbidly obese population. J Urol. 2008 Apr. 179(4):1401-6. [Medline].

  19. Ayoob R, Wang W, Schwaderer A. Body fat composition and occurrence of kidney stones in hypercalciuric children. Pediatr Nephrol. 2011 Dec. 26(12):2173-8. [Medline].

  20. Domrongkitchaiporn S, Ongphiphadhanakul B, Stitchantrakul W, Piaseu N, Chansirikam S, Puavilai G, et al. Risk of calcium oxalate nephrolithiasis after calcium or combined calcium and calcitriol supplementation in postmenopausal women. Osteoporos Int. 2000. 11(6):486-92. [Medline].

  21. Rodman JS, Mahler RJ. Kidney stones as a manifestation of hypercalcemic disorders. Hyperparathyroidism and sarcoidosis. Urol Clin North Am. 2000 May. 27(2):275-85, viii. [Medline].

  22. Whalley NA, Martins MC, Van Dyk RC, Meyers AM. Lithogenic risk factors in normal black volunteers, and black and white recurrent stone formers. BJU Int. 1999 Aug. 84(3):243-8. [Medline].

  23. Maloney ME, Springhart WP, Ekeruo WO, et al. Ethnic background has minimal impact on the etiology of nephrolithiasis. J Urol. Jun 2005. 173(6):2001-4.

  24. Rodgers AL, Lewandowski S. Effects of 5 different diets on urinary risk factors for calcium oxalate kidney stone formation: evidence of different renal handling mechanisms in different race groups. J Urol. 2002 Sep. 168(3):931-6. [Medline].

  25. Zerwekh JE. Bone disease and hypercalciuria in children. Pediatr Nephrol. 2010 Mar. 25(3):395-401. [Medline].

  26. Leslie S. Calcium and stone disease. Savitz GR, Leslie SW, eds. The Kidney Stones Handbook. 2nd ed. Roseville, Calif: Four Geez Press; 2000. 73-94.

  27. Corbin Bush N, Twombley K, Ahn J, Oliveira C, Arnold S, Maalouf NM, et al. Prevalence and spot urine risk factors for renal stones in children taking topiramate. J Pediatr Urol. 2013 Jan 31. [Medline]. [Full Text].

  28. Vachvanichsanong P, Malagon M, Moore ES. Recurrent abdominal and flank pain in children with idiopathic hypercalciuria. Acta Paediatr. 2001 Jun. 90(6):643-8. [Medline].

  29. Alon US, Berenbom A. Idiopathic hypercalciuria of childhood: 4- to 11-year outcome. Pediatr Nephrol. 2000 Sep. 14(10-11):1011-5. [Medline].

  30. Escribano J, Balaguer A, Martin R, Feliu A, Espax R. Childhood idiopathic hypercalciuria--clinical significance of renal calyceal microlithiasis and risk of calcium nephrolithiasis. Scand J Urol Nephrol. 2004. 38(5):422-6. [Medline].

  31. Arrabal-Polo MA, Arias-Santiago S, de Haro-Muñoz T, Lopez-Ruiz A, Orgaz-Molina J, Gonzalez-Torres S, et al. Effects of aminobisphosphonates and thiazides in patients with osteopenia/osteoporosis, hypercalciuria, and recurring renal calcium lithiasis. Urology. 2013 Apr. 81(4):731-7. [Medline].

  32. Fellström B, Backman U, Danielson B, Wikström B. Treatment of renal calcium stone disease with the synthetic glycosaminoglycan pentosan polysulphate. World J Urol. 1994. 12(1):52-4. [Medline].

  33. Norman RW, Scurr DS, Robertson WG, Peacock M. Inhibition of calcium oxalate crystallisation by pentosan polysulphate in control subjects and stone formers. Br J Urol. 1984 Dec. 56(6):594-8. [Medline].

  34. Senthil D, Subha K, Saravanan N, Varalakshmi P. Influence of sodium pentosan polysulphate and certain inhibitors on calcium oxalate crystal growth. Mol Cell Biochem. 1996 Mar 9. 156(1):31-5. [Medline].

  35. Prié D, Blanchet FB, Essig M, Jourdain JP, Friedlander G. Dipyridamole decreases renal phosphate leak and augments serum phosphorus in patients with low renal phosphate threshold. J Am Soc Nephrol. 1998 Jul. 9(7):1264-9. [Medline].

  36. Lemann J Jr, Pleuss JA, Gray RW, Hoffmann RG. Potassium administration reduces and potassium deprivation increases urinary calcium excretion in healthy adults [corrected]. Kidney Int. 1991 May. 39(5):973-83. [Medline].

  37. Martini LA, Cuppari L, Cunha MA, Schor N, Heilberg IP. Potassium and sodium intake and excretion in calcium stone forming patients. J Ren Nutr. 1998 Jul. 8(3):127-31. [Medline].

  38. Sebastian A, Hernandez RE, Portale AA, Colman J, Tatsuno J, Morris RC Jr. Dietary potassium influences kidney maintenance of serum phosphorus concentration. Kidney Int. 1990 May. 37(5):1341-9. [Medline].

  39. Curhan GC, Willett WC, Rimm EB, Stampfer MJ. A prospective study of dietary calcium and other nutrients and the risk of symptomatic kidney stones. N Engl J Med. 1993 Mar 25. 328(12):833-8. [Medline].

  40. Hiatt RA, Ettinger B, Caan B, Quesenberry CP Jr, Duncan D, Citron JT. Randomized controlled trial of a low animal protein, high fiber diet in the prevention of recurrent calcium oxalate kidney stones. Am J Epidemiol. 1996 Jul 1. 144(1):25-33. [Medline].

  41. Xu H, Zisman AL, Coe FL, Worcester EM. Kidney stones: an update on current pharmacological management and future directions. Expert Opin Pharmacother. 2013 Mar. 14(4):435-47. [Medline].

  42. Yendt ER, Gagne RJ, Cohanim M. The effects of thiazides in idiopathic hypercalciuria. Am J Med Sci. Apr 1966. 251(4):449-60.

  43. Howard JE, Thomas WC, Mukai T, et al. The calcification of cartilage by urine, and a suggestion for therapy in patients with certain kinds of calculi. Trans Assoc Am Physicians. 1962. 75:301-6.

  44. Breslau NA, Padalino P, Kok DJ, Kim YG, Pak CY. Physicochemical effects of a new slow-release potassium phosphate preparation (UroPhos-K) in absorptive hypercalciuria. J Bone Miner Res. 1995 Mar. 10(3):394-400. [Medline].

  45. Michaut P, Prié D, Amiel C, Friedlander G. Dipyridamole for renal phosphate leak?. N Engl J Med. 1994 Jul 7. 331(1):58-9. [Medline].

  46. Neer RM, Arnaud CD, Zanchetta JR, Prince R, Gaich GA, Reginster JY, et al. Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis. N Engl J Med. 2001 May 10. 344(19):1434-41. [Medline].

  47. Bushinsky DA, Laplante K, Asplin JR. Effect of cinacalcet on urine calcium excretion and supersaturation in genetic hypercalciuric stone-forming rats. Kidney Int. May 2006. 69(9):1586-92.

  48. Charytan C, Coburn JW, Chonchol M, et al. Cinacalcet hydrochloride is an effective treatment for secondary hyperparathyroidism in patients with CKD not receiving dialysis. Am J Kidney Dis. Jul 2005. 46(1):58-67.

  49. Dong BJ. Cinacalcet: An oral calcimimetic agent for the management of hyperparathyroidism. Clin Ther. Nov 2005. 27(11):1725-51.

  50. Lindberg JS, Culleton B, Wong G, et al. Cinacalcet HCl, an oral calcimimetic agent for the treatment of secondary hyperparathyroidism in hemodialysis and peritoneal dialysis: a randomized, double-blind, multicenter study. J Am Soc Nephrol. 16(3). Mar 2005:800-7.

  51. Cinacalcet: new drug. Secondary hyperparathyroidism: where are the clinical data?. Prescrire Int. 2006 Jun. 15(83):90-3. [Medline].

  52. Strohmaier WL, Schlee-Giehl K, Bichler KH. Osteocalcin response to calcium-restricted diet: a helpful tool for the workup of hypercalciuria. Eur Urol. 1996. 30(1):103-7. [Medline].

  53. Yousefichaijan P, Sharafkhah M, Cyrus A, Rafeie M. Therapeutic Efficacy of Hydrochlorothiazide in Primary Monosymptomatic Nocturnal Enuresis in Boys With Idiopathic Hypercalciuria. Nephrourol Mon. 2015 Sep. 7 (5):e29127. [Medline].

  54. Lee CT, Ng HY, Lee YT, Lai LW, Lien YH. The role of calbindin-D28k on renal calcium and magnesium handling during treatment with loop or thiazide diuretics. Am J Physiol Renal Physiol. 2015 Nov 18. ajprenal.00057.2015. [Medline].

  55. Pak CY, Odvina CV, Pearle MS, Sakhaee K, Peterson RD, Poindexter JR, et al. Effect of dietary modification on urinary stone risk factors. Kidney Int. 2005 Nov. 68(5):2264-73. [Medline].

Calcium-rich foods.
Table 1. Definitions of Hypercalciuria
Diet Definition
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
Table 2. Hypercalciuria Simplified Test Guideline
Hypercalciuria Diagnosis 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)

Normal Normal Normal Normal
Absorptive type I High Normal High
Absorptive type II Normal Normal High
Absorptive type III (renal phosphate leak) High High High
Renal leak High High High
Resorptive (hyperparathyroidism) High High High
Table 3. Calcium-Loading Test Interpretation Guide
Criteria Absorptive Type I

Vitamin D–Dependent (Classic Form)

Absorptive Type I

Vitamin D–Dependent (Variant Form)

Absorptive Type II

Dietary Calcium Responsive

Absorptive Type III

(Renal Phosphate Leak)

Renal Calcium Leak Resorptive
Urinary calcium on regular diet* High High High High High High
Urinary calcium on low-calcium diet High High NL High High High
Urinary calcium fasting NL High NL High High High
Urinary calcium after 1-g calcium load§ High High NL High High High
Serum PO4 (fasting) NL NL NL Low NL or high Low
Serum calcium (fasting) NL NL or high NL NL or high NL or low High
Serum PTH NL or low NL or low NL Low High High
Serum PTH after 1-g calcium load NL or low NL or low NL Low High High
Serum vitamin D-3 (calcitriol) NL High NL High High High
Fasting normocalciuria while on ketoconazole No Yes No Yes No No
Bone calcium density NL NL or low NL NL or low Low Low
NL = normal; PO4 = phosphate; PTH = parathyroid hormone.

* Regular diet is unrestricted calcium and sodium intake. Normal upper limit calciuria is < 4 mg/kg body weight per day.

Low-calcium diet is 400 mg calcium and 100 mEq of sodium per day. Normal upper limit calciuria is < 200 mg/day.

Fasting is a 12-hour fast. Normal upper limit is < 0.11 mg calcium/mg creatinine.

§ After 1-g calcium load, normal upper limit is < 0.20 mg calcium/mg creatinine.

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