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The excessive urinary calcium excretion, is the most common identifiable cause of calcium kidney stone disease.

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.

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.

More than 30 million Americans experience kidney stone disease, with 1.2 million new cases each year.

Idiopathic hypercalciuria is the most common metabolic abnormality in patients with calcium kidney stones.

Idiopathic hypercalciuria is diagnosed when clinical, laboratory, and radiographic investigations fail to delineate an underlying cause of the condition.

It is a polygenic trait and is significantly influenced by diet.

Secondary hypercalciuria occurs when a known process produces excessive urinary calcium.

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.

Hypercalciuria 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

The following are the most common types of clinically significant hypercalciuria:

Absorptive hypercalciuria

Renal phosphate leak hypercalciuria

Renal leak hypercalciuria

Resorptive hypercalciuria. 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.

Hypercalciuric stone formers have been demonstrated to have a lower average bone mineral density than non–stone formers matched for age and sex.

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.

Serum calcium, creatinine, and phosphate studies, should be performed to identify patients at risk for hyperparathyroidism, renal failure, and renal phosphate leak.

Associated with insulin resistance associated with obesity and increased intestinal absorption and urinary excretion of calcium.

Efforts are made to formally study the exact cause of the hypercalciuria: 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.

Initial blood and 24-hour urine testing identifies hypercalciuric patients.

Check hypercalcemic patients for hyperparathyroidism with parathyroid hormone (PTH) levels.

A thiazide challenge test if the PTH level alone is inconclusive, may be helpful.

Dietary components associated with increased urinary calcium excretion included high salt, high animal proteins, and sucrose intake.

Recommendations in the dietary treatment of hypercalciuria:

Limit daily calcium intake to 600-800 mg/day.

Limit dietary oxalate, especially when calcium intake is reduced.

High oxalate levels are found in strong teas; nuts; chocolate; coffee; colas; green, leafy vegetables and other plant and vegetable products.

Avoid excessive purines and animal protein.

Reduce sodium 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.

Medications used in the treatment : include Diuretics – Thiazides, indapamide, and amiloride Orthophosphates – Neutral phosphate Bisphosphonates – Alendronate Calcium-binding agents – Sodium cellulose phosphate.

It contributes to osteoporosis.

Hypercalciuria can be classified as idiopathic or secondary.

Idiopathic hypercalciuria is diagnosed when clinical, laboratory, and radiographic studies fail to delineate an underlying cause.

Secondary hypercalciuria is a process produced by excessive urinary calcium.

Elevated urinary calcium occurs by 3 primary mechanisms:

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.

Optimal levels of urinary calcium have not been determined, and may not be reliable when applied to nephrolithiasis.

The Nurses’ Health Study and the Health Professional Follow-up Study indicate that the relative risk of stone production appears to be continuous, rather than with a single arbitrary level that differentiates healthy people from those who form stones.

The urinary calcium concentration is a reliable indicator of stone formation risk.

The most common types of clinically significant hypercalciuria:

Absorptive hypercalciuria

Renal phosphate leak hypercalciuria

Renal leak hypercalciuria

Resorptive hypercalciuria

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.

Calcium absorption occurs mainly in the duodenum.

Calcium absorption represents only about 20% of the ingested dietary calcium.

With increased intestinal calcium absorption there is an increase in serum calcium levels.

Parathyroid hormone (PTH) level is low or in the low-normal range in absorptive hypercalciuria, because the serum calcium level is generally high.

Mild-moderate absorptive hypercalciuria is usually controlled with dietary restriction of calcium.

Absorptive hypercalciuria type I is a relatively rare condition, generally characterized by elevated urinary calcium and calcium/creatinine levels except while fasting.

Ketoconazole is a potent P450 3A4 cytochrome inhibitor that reduces circulating vitamin D-3 levels by 30-40%.

A serum phosphate level of less than 2.9 mg/dL can cause renal phosphate leak hypercalciuria.

Loss of phosphate in the urine due to a renal defect,produces hypophosphatemia, which stimulates the renal conversion of 25-hydroxyvitamin D to the much more active 1,25-dihydroxyvitamin D-3.

Vitamin D-3 increases intestinal phosphate absorption to correct the low serum phosphate levels, and simultaneously increases intestinal calcium absorption.

Renal leak hypercalciuria occurs in about 5-10% of calcium-stone formers.

Renal leak hypercalciuria is characterized by fasting hypercalciuria with secondary hyperparathyroidism but without hypercalcemia.

In renal leak hypercalciuria there is a defect in calcium reabsorption from the renal tubule that causes excessive urinary calcium loss, resulting in hypocalcemia, which causes an elevation in the serum PTH.

This secondary hyperparathyroidism raises vitamin-D levels and increases intestinal calcium absorption.

A 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.

Resorptive hypercalciuria is almost always due to hyperparathyroidism, and accounts for 3-5% of all cases of hypercalciuria.

Resorptive hypercalciuria increases PTH levels cause a release of calcium from bone stores, and 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, in resorptive hypercalciuria, hypercalcemia overcomes this renal calcium–conserving quality and results in an increased net loss of calcium through the urine, hypercalciuria.

Association between obesity and kidney stones is well documented.

Hyperparathyroidism does not always result in calcium-stone disease.

Any level of serum calcium, patients with hyperparathyroidism have lower urinary calcium excretion than do patients with hypercalcemia who have normal PTH levels, due to the calcium-conserving effect of PTH on the kidneys.

Hyperparathyroidism should be suspected in calcium stone–forming patients with significant hypercalciuria.

Patients with hyperparathyroidism who undergo parathyroid surgery and subsequently demonstrate normal urinary calcium levels are still at risk for developing stones.

Urinary excretion of calcium is the result of the interplay of the gastrointestinal tract, the kidney, and bone and is regulated by multiple hormones.

Patients with idiopathic hypercalciuria have an increase in calcium turnover, increased gut calcium absorption, decreased renal calcium reabsorption, and a tendency to lose calcium from bone.

There is an increased incidence of hypercalciuria is observed in first-degree relatives of individuals with idiopathic hypercalciuria.

In some increased tissue vitamin D response may be responsible for manifestations of idiopathic hypercalciuria.

A 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.

Dysregulation of the calcium-sensing receptor, Claudin-14 axis, likely contributes to the development of hypercalciuria.

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 plateaus at about 500 mg of calcium for most people.

Oral calcium dose is absorbed better if administered in small, divided portions rather than in a single large calcium bolus.

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.

Causes of hypercalciuria:


Renal tubular acidosis

Sarcoidosis and other granulomatous diseases

Vitamin D intoxication

Glucocorticoid excess

Paget disease

Albright tubular acidosis

Various paraneoplastic syndromes

Prolonged immobilization

Induced hypophosphatemic states

Multiple myeloma



Metastatic tumors, especially involving bone

Addison disease

Milk-alkali syndrome

It is present in 91.9% of subjects on deferasirox, an oral iron chelator.

Higher frequency of hypercalciuria and hyperuricosuria in children with vesicoureteral reflux.

The cause of idiopathic hypercalciuria is not known.

Some studies report increased absorption of calcium from the intestine, independent of vitamin D or a result of increased gut sensitivity to vitamin D.

In some patients with hypercalciuria, the proportion of calcium excreted into the urine is higher than normal, regardless of dietary intake of calcium.

Some patients have been found to have higher than normal urinary calcium despite lower than normal dietary intake, suggesting decreased renal tubular reabsorption.

Some patients have an imbalance of calcium deposition and reabsorption in bone that is independent of PTH or vitamin D.

A combination of the above factors may contribute to the high amounts of urinary calcium observed in patients with idiopathic hypercalciuria.

Pregnancy has been thought to increase the incidence of urinary stones and hypercalciuria.

Non–stone-producing pregnant women have been found to have hypercalciuria during all 3 trimesters.

Calcium supplementation, does not increase the risk of calcium urolithiasis significantly in healthy postmenopausal women, even if they have increased urinary calcium excretion.

Women administered calcium and calcitriol did have a significant increase in their urinary calcium levels, but did not result in any increase in overall stone risk.

Many cases of absorptive hypercalciuria involve elevated vitamin-D levels.

Vitamin D increases small-bowel absorption of calcium and phosphate, and enhances renal filtration, decreases PTH levels, and reduces renal tubular calcium absorption, which ultimately leads to hypercalciuria.

About 30-40%, of patients with absorptive hypercalciuria demonstrate abnormally elevated vitamin D3 levels.

In some patients with sarcoidosis, 1,25-dihydroxyvitamin D is synthesized in an uncontrolled fashion by macrophages in the sarcoid granulomas, producing a hypervitaminosis-D state with hypercalcemia and, frequently, hypercalciuria.

Management in sarcoidosis hypercalciuria includes limiting sunlight exposure and reducing vitamin D ingestion.

Glucocorticoid administration usually controls the hypercalcemia and hypercalciuria of sarcoidosis.

Hypercalciuria has been estimated to be at least 1 in 3 among people who form kidney stones.

It is the most common metabolic abnormality found with calcium nephrolithiasis.

The stone belt is primarily the southeast portion of the United States, yet no clear biochemical difference was found when risk factors were compared among various regions of the country.

The overall risk of forming stones differs in various regions: 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.

Bladder stones are predominant in developing countries and are related to poor socioeconomic conditions.

Caucasians tend to have stones more often than do black individuals, yet racial groups tested (white, black, Asian, Hispanic) demonstrated remarkable similarity in the incidence of underlying metabolic abnormalities.

The urinary calcium excretion for men generally is 275 mg or less per day, whereas in women the usual daily limit is only 250 mg.

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.

Hypercalciuria is more common in postmenopausal women than men.

Obesity is a risk factor for kidney stone disease in women but not in men.

Body size is a positive risk factor for kidney stone disease in women, but the correlation was much less significant in men.

High-dose vitamin B-6 appears to be beneficial in women with calcium oxalate stone disease but probably not in men.

Women who take large amounts of vitamin B-6 had a significantly lower incidence of new calcium oxalate stone formation, but a similar benefit was not noted in men.

Carbohydrate intake was found to be a kidney stone dietary risk factor for women but not for men.

Studies found no benefit to dietary vitamin-C modifications in either men or women.

The peak age range for calcium kidney stone production is generally 35-45 years.

Another peak incidence of hypercalciuria occurs in postmenopausal women, as many women are taking supplemental calcium for osteoporosis prophylaxis or therapy.

Postmenopausal women are at an increased risk of hyperparathyroidism, which can cause hypercalciuria.

Geriatric stone disease is relatively uncommon, as the risk for newly formed stones in patients older than 65 years is quite low.

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.

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.

It can occur at any age, including in newborns.

The peak incidence of idiopathic hypercalciuria in children occurs at age 4-8 years.

Hypercalciuria morbidity is related to kidney stone disease and bone demineralization leading to osteopenia and osteoporosis.

Painful kidney stones occur because of the stretching, dilating, and spasm of the ureter and kidney caused by the acute obstruction.

Kidney stone pain is unrelated to the size of the stone or its composition and is related only to the rapidity and degree of the obstruction.

Hypercalciuric stone formers have a 5-15% lower average bone mineral density than non–stone formers matched for age and sex.

Female hypercalciuric stone formers who become menopausal are at significantly greater risk of osteoporosis than their healthy female counterparts, and the higher the urinary calcium excretion is, the greater the risk.

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.

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