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calcium in urine

Calcium in urine

Calcium is the most abundant and one of the most important minerals in your body. An average human body contains 1 kg of the calcium. Calcium is essential for cell signaling and the proper functioning of muscles, nerves, and the heart. Calcium is needed for blood clotting and is crucial for the formation, density, and maintenance of bones and teeth. The body normally keeps serum and intracellular calcium levels under tight control through bone resorption and urinary excretion.

About 99% of calcium is found complexed in the bones, while the remaining 1% circulates in the blood. Calcium levels are tightly controlled; if there is too little absorbed or ingested, or if there is excess loss through the kidney or gut, calcium is taken from bone to maintain blood concentrations. Roughly half of the calcium in your blood is “free” and is metabolically active (see Figure 1). The remaining half is “bound” to proteins, primarily albumin and to a lesser extend globulins, with a smaller amount complexed to anions, such as phosphate, and these bound and complexed forms are metabolically inactive. There are two tests to measure blood calcium. The total calcium test measures both the free and bound forms. The ionized calcium test measures only the free, metabolically active form.

Blood calcium level is maintained by the parathyroid hormone (PTH). Parathyroid hormone (PTH) indirectly increases the absorption of calcium from the gastrointestinal tract by the production of the vitamin D. Parathyroid hormone (PTH) increases the serum calcium level by increasing bone resorption and mobilizing calcium. Urine calcium is high in 30% to 80% of cases of primary hyperparathyroidism, but it does not diagnostic.

Some calcium is lost from the body every day, filtered from the blood by the kidneys and excreted into the urine and sweat. Measurement of the amount of calcium in the urine is used to determine how much calcium the kidneys are eliminating. Urinary calcium excretion is dependant upon the dietary intake of calcium.

Calcium excretion:

  • Mostly calcium is lost in the stool.
  • The very small amount is excreted in urine.
  • In hypercalcemia, there is increased secretion of calcium in the urine.
  • In hypocalcemia, there is decreased secretion of calcium in the urine.

Increased calcium in urine takes place due to:

  • Increased intestinal calcium absorption.
  • The defect in the renal tubular reabsorption.
  • Loss or reabsorption from the bone.
  • Or a combination of the above possibilities.

A total calcium level is often measured as part of a routine health screening. It is included in the comprehensive metabolic panel (CMP) and the basic metabolic panel (BMP), groups of tests that are performed together to diagnose or monitor a variety of conditions.

When an abnormal total calcium result is obtained, it is viewed as an indicator of an underlying problem. To help diagnose the underlying problem, additional tests are often performed to measure ionized calcium, urine calcium, phosphorus, magnesium, vitamin D, parathyroid hormone (PTH) and PTH-related peptide (PTHrP). Parathyroid hormone (PTH) and vitamin D are responsible for maintaining calcium concentrations in the blood within a narrow range of values.

If the blood calcium is abnormal, measuring calcium and PTH together can help determine whether the parathyroid glands are functioning normally. Measuring urine calcium can help determine whether the kidneys are excreting the proper amount of calcium, and testing for vitamin D, phosphorus, and/or magnesium can help determine whether other deficiencies or excesses exist. Frequently, the balance among these different substances (and the changes in them) is just as important as the concentrations.

Calcium can be used as a diagnostic test if a person has symptoms that suggest:

  • Kidney stones
  • Bone disease
  • Neurologic disorders

Total calcium is the blood test most frequently ordered to evaluate calcium status. In most cases, it is a good reflection of the amount of free calcium present in the blood since the balance between free and bound is usually stable and predictable. However, in some people, the balance between free and bound calcium is disturbed and total calcium is not a good reflection of calcium status. In these circumstances, the measurement of ionized calcium may be necessary. Some conditions where ionized calcium should be the test of choice include: critically ill patients, those who are receiving blood transfusions or intravenous fluids, patients undergoing major surgery, and people with blood protein abnormalities like low albumin.

Large fluctuations in ionized calcium can cause the heart to slow down or to beat too rapidly, can cause muscles to go into spasm (tetany), and can cause confusion or even coma. In those who are critically ill, it can be extremely important to monitor the ionized calcium level in order to be able to treat and prevent serious complications.

Figure 1. Calcium exists in three forms in the blood

calcium in blood

Figure 2. Calcium metabolism and control

Calcium metabolism and control

Normal urine calcium levels

The reference ranges of urinary calcium are dependent on the diet and the ability of its intestinal absorption.

  • Males: 25-300 mg/24-hour specimen*
  • Females: 20-275 mg/24-hour specimen*
  • Hypercalciuria (high calcium in urine): >350 mg/24-hour specimen

*These levels are reflective of individuals with average, unrestricted calcium intake, which is 600-800 mg/day.

For persons with an average daily calcium intake of 600-800 mg, daily calcium excretion is normally as follows:

  • Males: 25-300 mg /24-hour specimen
  • Females: 20-275 mg /24-hour specimen

Furthermore, accurate interpretation of urine calcium concentration should be done in relation to glomerular filtrate, considering the following equation:

  • Calcium in urine (mg/100 ml glomerular filtrate) = [calcium in urine (mg/dl) X serum creatinine (mg/dl)] / urine creatinine (mg/dl)

Young children and infants tend to have higher urinary calcium excretion and lower urinary creatinine levels, so the suggested normal limits for calcium/creatinine ratios differ by age as follows 1:

  • Up to six months of age: less than 0.8 calcium/creatinine ratio
  • Six to twelve months of age: less than 0.6 calcium/creatinine ratio
  • 24 months and older: less than 0.2 calcium/creatinine ratio

High calcium in urine

In clinical practice, a 24-hour urinary calcium level of 250 mg is a useful initial threshold for determining high calcium in urine also known as hypercalciuria. In children, a ratio of more than 4 mg calcium/kg body weight, a random calcium/creatinine ratio of more than 0.18, or a 24-hour urinary calcium concentration of more than 200 mg/liter may be more useful. High calcium in urine or 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.

Definitions of hypercalciuria:

  • Regular diet (unrestricted)
    • Women: Urinary excretion >250 mg calcium (6.2 mmol/24 hour)
    • Men: Urinary excretion >275-300 mg calcium (7.5 mmol/24 h)
    • OR
      • 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

In practice, it often is used to identify whichever method gives the most abnormal reading and try to “optimize” it 2. Spot urinary chemistry has shown poor sensitivity and specificity for hypercalciuria which is why the 24 hour urine test is so critical in making the diagnosis 3.

High levels of calcium in urine (hypercalciuria) is generally considered to be the most common identifiable metabolic risk factor for calcium kidney stone disease (nephrolithiasis). 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.  High levels of calcium in urine also contributes to osteopenia and osteoporosis. Post menopausal women with osteoporosis and no history of kidney stones have a 20% chance of having high calcium in urine. High levels of calcium in urine significance is primarily due to these two clinical entities: kidney stone formation (nephrolithiasis) and bone resorption. High calcium in urine occurs in 5% to 10% of the adult population and is found in about one-third of all calcium stone formers. Close relatives of hypercalciuric patients tend to have an increased rate of high calcium in urine themselves. Up to 40% of the first and second-degree relatives of hypercalciuric recurrent stone formers will also have high calcium in urine 4. There are more than 30 million kidney stone patients and 1.2 million new kidney stone cases every year in the United States with one-third of them demonstrating hypercalciuria when tested.

On average, high calcium in urine stone formers have decreased bone mineral density than matched controls which are neither stone formers nor hypercalciuric 5. Even among kidney stone patients, those with high levels of calcium in urine (hypercalciuria) will have average bone calcium density measurements 5% to 15% lower than their normocalciuric peers 2.

The definition of high calcium in urine can be a bit confusing. Traditionally, it has been defined as daily urinary calcium excretion of greater than 275 mg in men and greater than 250 mg in women. This definition ignores concentration, age, renal function, and weight considerations as well as the obvious question of whether a different normal excretion amount is reasonable based solely on gender 2.

High calcium in urine also can be defined as a daily urinary excretion of more than 4 mg calcium/kg body weight. This definition is somewhat more useful in the pediatric age group if the child is over two years old; but in adults, it tends to allow higher urinary calcium excretions in heavier and obese individuals compared to lighter patients. One solution is to use 24-hour urinary calcium concentration (less than 200 mg calcium/liter urine is normal” but less than 125 mg calcium/liter is optimal) 3.

Another clinically useful definition, especially in pediatrics, is the random or spot urinary calcium/creatinine ratio (less than 0.2 mg calcium/creatinine mg is normal while less than 0.18 mg calcium/creatinine mg is optimal). Its benefit is that it does not necessarily need a 24-hour urine collection with every visit just to track high calcium in urine. 6.

Which definition to use depends on the clinical situation and the availability of reliable 24-hour urine collection data. For optimal results, one approach is to look at all of the definitions and concentrate treatment on optimizing the worst of them. This “optimization” approach focuses less on what is normal and more on what an optimal level would be for a calcium stone forming patient. This type of optimization also can be used for other urinary chemical risk factors besides high calcium in urine 2.

High calcium in urine causes

High calcium in urine or hypercalciuria can be classified as idiopathic hypercalciuria or secondary hypercalciuria. 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 traditional way of looking at high calcium in urine includes absorptive hypercalciuria which has increased intestinal calcium absorption, renal calcium leak which is an inherent kidney problem, resorptive as in hyperparathyroidism, and renal phosphate leak high calcium in urine. Not every patient will fall nicely into one of these categories, and a simpler classification requiring much less testing is now available based on clinical response 5.

Other causes of high calcium in urine include milk-alkali syndrome (excessive oral calcium ingestion), sarcoidosis, glucocorticoid excess, Paget disease, paraneoplastic syndrome, multiple myeloma, metastatic tumors involving bone, Addison disease, and Hypervitaminosis D. high calcium in urine without any obvious cause, which is the majority of cases, is called idiopathic 7.

Animal studies have suggested that in some subjects, there appears to be an increased sensitivity to Vitamin D. This may be due to an increased number of 1,25 Vitamin D receptors in those individuals. These changes have not been reliably identified in humans; just in animal studies 8.

High salt (sodium) intake has also been suggested as a possible cause of high calcium in urine. An increased sodium load leads to higher urinary excretion of sodium which decreases tubular calcium reabsorption resulting in high calcium in urine. While high salt intake may be a contributing factor, it is rarely the sole cause of significant high calcium in urine 3.

A high animal protein diet will produce an acid load that causes a release of calcium from the bone and inhibition of renal tubular calcium reabsorption resulting in high calcium in urine. Again, this does not appear to be the sole causes of significant high calcium in urine 9.

The following are the most common types of clinically significant high calcium in urine:

  • Absorptive hypercalciuria
  • Renal phosphate leak hypercalciuria (also known as absorptive hypercalciuria type III)
  • Renal leak hypercalciuria
  • Resorptive hypercalciuria – This is almost always caused by hyperparathyroidism

The following conditions increase daily calcium in urine excretion:

  • Hyperparathyroidism
  • Osteolytic bone metastases
  • Breast cancer
  • Multiple myeloma
  • Osteoporosis 10
  • Vitamin D and A intoxication 11
  • Distal renal tubular acidosis
  • Idiopathic hypercalciuria
  • Thyrotoxicosis
  • Paget disease
  • Fanconi syndrome
  • Hepatolenticular degeneration
  • Prolonged immobilization
  • Renal diseases.
  • Schistosomiasis
  • Sarcoidosis
  • Urinary bladder cancers
  • Osteitis deformans

The following drugs are also sources of increased daily calcium in urine excretion:

  • Calcium salts
  • Acetazolamide
  • Cholestyramine
  • Corticosteroids
  • Dihydrotachysterol
  • Initial diuretic use – Eg, furosemide
  • Excessive litium (via inducing hyperparathyroidism) 11
  • Excesive administration of parathyroid hormone (PTH)

Absorptive hypercalciuria is the most common type of excessive urinary calcium excretion 5. Absorptive hypercalciuria (increased calcium absorption by the gut leading to high excretion of calcium in the urine) may be reduced with dietary restriction. This distinguishes these patients from those whose hypercalciuria has resulted from hyperthyroidism, hyperparathyroidism, or Paget disease, as well as from persons with “renal leak” calciuria (which occurs in renal tubular acidosis) 12. Absorptive hypercalciuria is found in about 50% of all calcium stone forming patients. Increased gastrointestinal calcium absorption increases serum calcium levels while lowering serum Vitamin D and parathyroid hormone levels. Only about 20% of ingested calcium is absorbed, normally taking place in the duodenum. A Vitamin D dependent version of absorptive high calcium in urine can be identified by high serum Vitamin D levels 2.

Renal phosphate leak hypercalciuria also known as absorptive hypercalciuria type 3, is perhaps the most interesting from a pathophysiological point of view. A renal defect causes excessive urinary phosphate excretion which leads to hypophosphatemia. This induces higher Vitamin D activation in the kidney which increases intestinal phosphate absorption to correct the low serum phosphate. Unfortunately, the extra Vitamin D also increases intestinal calcium absorption. The extra calcium absorbed is eventually excreted in the urine resulting in high calcium in urine. This type of high calcium in urine is vitamin D dependent and is relatively unresponsive to thiazides. The diagnosis is made by the findings of low or low-normal serum phosphate, high calcium in urine, high urinary phosphate, and high serum Vitamin D3 levels with normal serum calcium and parathyroid hormone (PTH) levels 2. Vitamin D levels can help detect renal phosphate leak hypercalciuria (where Vitamin D is elevated along with high urinary but low serum phosphate levels). High Vitamin D levels and possible renal phosphate leak hypercalciuria should be suspected in patients who do not respond to adequate thiazide therapy 13.

Renal leak hypercalciuria is found in about 5% to 10% of hypercalciuric stone formers. It is caused by a renal defect that causes an obligatory loss of calcium in the urine regardless of serum calcium levels or dietary calcium intake. This is usually accompanied by hypocalcemia and an increase in serum parathyroid hormone (PTH) levels. The calcium/creatinine ratio tends to be high in this condition (usually greater than 0.20), and there is an association with Medullary Sponge Kidney 2.

Resorptive hypercalciuria accounts for only about 3% to 5% of all hypercalciuric patients and is almost always due to hyperparathyroidism. Sustained, inappropriate, and excessive serum parathyroid hormone causes a release of calcium from the bone leading to osteopenia and hypercalcemia. Eventually, the hypercalcemia overcomes the normal parathyroid hormone effect of decreasing urinary calcium excretion, and the result is high calcium in urine (e.g., similar to spilling sugar in the urine in diabetics). This explains why high calcium in urine from hypercalcemia is less for any given elevated serum calcium level in patients with hyperparathyroidism than in other patients who are hypercalcemic 2.

Pregnancy increases high calcium in urine during all three trimesters, but this does not appear to increase the risk of new stone disease as there is also an increase in kidney stone inhibitors.

Hyperparathyroidism should be suspected in all adult with high calcium in urine and elevated or borderline elevated serum calcium levels. It can be diagnosed simply by checking a parathyroid hormone level in those individuals 14.

In children 2-12 years of age, the calcium/citrate ratio has been found to be useful clinically. A cutoff of 0.25 has been suggested meanting that those with a calcium/citrate ratio >0.25 are more likely to develop stones 1.

In children, there is an apparent connection between recurrent abdominal pain and high calcium in urine. A recent study has connected hypercalciuric pediatric kidney stone patients with an increase in their urinary excretion of lipid metabolism/transport-related proteins. This suggests that abnormalities in lipid metabolism may be responsible or connected in some way to pediatric high calcium in urine and nephrolithiasis 1.

Cortical bone is more affected by high calcium in urine than cortical bone. Interestingly, bone mineral density is inversely related with high calcium in urine in nephrolithiasis patients but not in patients without nephrolithiasis 15.

Dent disease

Dent disease is a rare, X-linked hereditary disorder that primarily affects the proximal renal tubules resulting in hypercalciuria and proteinuria starting in childhood. It may progress from there, leading to osteomalacia, short stature, nephrocalcinosis, nephrolithiasis, hypophosphatemia and eventually renal failure. Up to 80% of affected males will develop end-stage renal failure by age 50. Vitamin D levels (1,25 (OH)2 Vit. D) are elevated or in the high normal range while parathyroid hormone levels are low. There are only about 250 families known to carry this disorder, so the incidence is quite low 16.

Treatment is based on controlling hypercalciuria and preserving renal function. While this can be done with thiazide diuretics, the hypercalciuria almost always responds to dietary therapy. ACE inhibitors and citrate supplements are used in children with the disorder to help preserve renal function, but their effectiveness is unclear 16.

High calcium in urine symptoms

There is no specific clinical finding of high calcium in urine itself, but it should be suspected in cases of calcium kidney stone disease (nephrolithiasis), nephrocalcinosis, hypercalcemia, hyperparathyroidism, osteopenia and osteoporosis. High calcium in urine also can cause hematuria even without any detectable stone formation, particularly in children. The cause is thought to be from focal and microscopic tissue damage from tiny calcium crystals and focal stones that are too small to be diagnosed with standard techniques. Urinary testing makes the definitive diagnosis.

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 17.

Pediatric patients

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:

  • Dysuria (pain or discomfort when urinating)
  • Abdominal pain
  • Irritability (infants)
  • Urinary frequency
  • Urinary urgency
  • Change of urinary appearance
  • Colic
  • Daytime incontinence
  • Isolated or recurrent urinary tract infections 18
  • Vesicourethral reflux 19

High calcium in urine diagnosis

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. [4]

In addition, imaging studies may be helpful in identifying underlying renal abnormalities or nephrolithiasis.

Traditional workup

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

Simplified workup

  • 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

High calcium in urine treatment

If serum calcium levels are normal, which rules out hyperparathyroidism, first try dietary modifications, such as avoiding excessive dietary calcium intake and lowering dietary animal protein (< 1.7 g/kg of body weight) and maintaining a low salt (sodium) diet is recommended 2. 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. Increase fluid intake, especially water (sufficient to produce at least 2 L of urine per day). Increase dietary fiber (12-24 g/day). Then, a repeat 24-hour urine test can be done to determine the response 14. If high calcium in urine persists, then medication such as thiazides likely will be needed. If thiazides fail, even after adjusting the dose and moderating sodium intake (which negates the hypocalciuric effect of the thiazides), then the patient could have renal phosphate leak high calcium in urine which does not typically respond to thiazide-type medications 3. Start orthophosphate therapy. Additional medications that can help control hypercalciuria include amiloride and potassium citrate 2.

Orthophosphate therapy not only increases serum phosphate levels, which naturally lower Vitamin D3 activation, but also increases renal calcium reabsorption and urinary stone inhibitors like pyrophosphate. They also may act as gastrointestinal calcium binders to help reduce absorption. Orthophosphates can reduce urinary calcium excretion by up to 50% and may be given together with thiazides when necessary. However, they are most useful in cases where thiazides have failed or cannot be used as well as for renal phosphate leak high calcium in urine 3.

Amiloride, a potassium-sparing diuretic, is not a thiazide but when added to thiazides may further increase calcium reabsorption as well as minimizing potassium loss. Amiloride is not usually recommended with potassium citrate due to the potential for hyperkalemia. Triamterene is not recommended in stone formers as it can form triamterene calculi 20.

Thiazides can induce a positive calcium balance and reduce urinary calcium by up to 50%. Hydrochlorothiazide and chlorthalidone are used most often, but indapamide also can be used. The advantage of chlorthalidone and indapamide is their longer half-life as hydrochlorothiazide would need to be given twice a day. Thiazides will not be effective unless dietary salt intake is limited. For every gram of daily dietary salt decrease, 24 hour urinary calcium would be expected to drop by 5.46 mg 3.

Thiazides will also tend to reduce serum potassium, increase uric acid levels, and lower urinary citrate excretion. For that reason, it often is useful to add potassium citrate to these patients when they start on thiazide therapy 2.

When thiazides fail even at adequate dosages in patients with reasonable sodium restriction, it could be due to a Vitamin D-dependent form of high calcium in urine such as Renal Phosphate Leak. This variant can be treated with orthophosphates, which generally lower serum Vitamin D, or with ketoconazole which blocks cytochrome P450 3A4 resulting in a 30% to 40% reduction in circulating Vitamin D3 levels 2.

Potassium citrate therapy will not only increase urinary citrate levels, but it may also increase renal calcium reabsorption reducing high calcium in urine 21.

In children, treatment of high calcium in urine is primarily dietary, at least initially. Calcium intake should not be restricted unless it exceeds the usual recommended amount. Vitamin D supplementation should be avoided, and dietary animal protein intake should be limited to within the usually recommended limits. A 3 to 6 month trial of dietary measures alone is reasonable before resorting to thiazide medications 1.

Low calcium in urine

The following conditions decrease daily calcium in urine excretion:

  • Pseudohypoparathyroidism
  • Hypoparathyroidism
  • Rickets
  • Osteomalacia
  • Nephrotic syndrome 22
  • Acute glomerulonephritis
  • Osteoblastic bone metastases (e.g., metastatic prostate cancer)
  • Hypothyroidism
  • Celiac disease
  • Preeclampsia
  • Acute renal failure, nephritis, and nephrosis
  • Steatorrhea
  • Sprue disease
  • Hypocalciuric hypercalcemia (Familial hypocalciuric hypercalcemia) 23
  • Gitelman syndrome
  • Bartter syndrome
  • Vitamin D deficiency

Daily calcium urine excretion can also be reduced by the following drugs:

  • Aspirin
  • Bicarbonate
  • Chronic diuretic use (eg, thiazides, chlorthalidone)
  • Estrogens
  • Indomethacin
  • Lithium (well-controlled doses)
  • Neomycin
  • Oral contraceptives
References
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  9. Prezioso D, Strazzullo P, Lotti T, Bianchi G, Borghi L, Caione P, Carini M, Caudarella R, Ferraro M, Gambaro G, Gelosa M, Guttilla A, Illiano E, Martino M, Meschi T, Messa P, Miano R, Napodano G, Nouvenne A, Rendina D, Rocco F, Rosa M, Sanseverino R, Salerno A, Spatafora S, Tasca A, Ticinesi A, Travaglini F, Trinchieri A, Vespasiani G, Zattoni F., CLU Working Group. Dietary treatment of urinary risk factors for renal stone formation. A review of CLU Working Group. Arch Ital Urol Androl. 2015 Jul 07;87(2):105-20.
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