Hypercalciuria

What is Hypercalciuria?

Hypercalciuria, or high levels of calcium in your urine, is often the most common factor discovered in people who regularly form calcium kidney stones. This condition can also contribute to weakened bones in conditions known as osteopenia and osteoporosis. Its significance mainly relates to these two health problems: kidney stones and bone breakdown. The majority of all kidney stones, up to 85%, are calcium-based (calcium oxalate and calcium phosphate). Hypercalciuria is the main cause of unexplained calcium kidney stones. Those with this condition, on average, have less dense bones compared to individuals who neither form stones nor have hypercalciuria. Kids with kidney stones who also have hypercalciuria typically show bone density levels 5% to 15% lower than their peers. The long-term effects are currently unknown.

Defining hypercalciuria can be confusing. It is traditionally identified if daily urinary calcium excretion surpasses 275 mg in men, or 250 mg in women. But this definition does not consider concentration, age, kidney function, weight, or gender-based standards. Another definition describes it as a daily urinary outflow of more than 4 mg calcium/kg of body weight. This definition works better for children older than two years. In adults, it may result in allowable higher urinary calcium in heavier individuals compared to lighter ones. A potential solution could be using the 24-hour urinary calcium concentration, with less than 200 mg calcium/liter of urine as “normal”, and less than 125 mg calcium/liter of urine as “optimal”.

A particularly useful definition, especially for children, 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. The benefit of this method is that it doesn’t require a full 24-hour urine collection before each doctor’s visit to monitor hypercalciuria.

The definition you choose to use depends on your situation and the availability of reliable 24-hour urine collection data. For best results, one approach is to review all definitions and focus treatment on improving the most serious of them. This “optimization” approach focuses less on the “normal” level and more on the best level for a patient prone to forming calcium kidney stones. This kind of optimization can also apply to other urinary chemical risk factors beyond hypercalciuria.

Young children and babies tend to have higher urinary calcium levels and lower urinary creatinine levels, so the recommended normal limits for calcium/creatinine ratios vary by age as follows:

Up to six months of age: less than 0.8
Six to twelve months of age: less than 0.6
24 months and older: less than 0.2

What Causes Hypercalciuria?

Most of the calcium in our blood (>60%) gets filtered by the kidneys and put back into the blood in an area called the proximal tubule. Here, special proteins called claudins help this process. The rest of the calcium is reabsorbed in the different part of the kidney, the loop of Henle, using different types of claudins. Vitamin D can slow down the work of Claudins. When there’s less magnesium in our blood, Claudins can work more to balance it.

The calcium that is left after this is either expelled or reabsorbed in the distal convoluted tubule and collecting ducts, which have their own chemical processes. Usually, if someone has too much calcium in their urine (hypercalciuria), it’s because one of these calcium reabsorption processes is not working correctly because of some genetic change.

Traditionally, doctors have broken down hypercalciuria into four categories:

1. Absorptive – too much calcium getting absorbed from our intestines.
2. Renal calcium leak – the kidney has a problem that causes it to leak calcium.
3. Resorptive – occurs in a disease called hyperparathyroidism.
4. Renal phosphate leak hypercalciuria – another problem with the kidneys.

However, not everyone fits perfectly into these categories because there can be combinations of these problems.

Many health problems can also increase the amount of calcium in urine, like Addison disease, certain genetic conditions, excess steroids, overactive thyroid, too much vitamin D, bone cancers, too much calcium in diet, Multiple myeloma, Paget disease, and other diseases related to the kidneys, bones, and immune system.

Research done on animals shows they are extra sensitive to vitamin D, which might be why they have too much calcium in their urine. However, we don’t know for sure if this is the same for humans.

It’s also possible that a diet high in salt could cause hypercalciuria. That’s because more salt in the body leads to more salt being expelled in urine, decreasing how much calcium can be absorbed back into the blood in the kidneys, and therefore causing more calcium to be in urine. But this is rarely the sole reason for someone having too much calcium in their urine.

Similarly, a diet high in animal protein could cause too much calcium in urine. This is due to the high quantity of acid that is produced, which triggers the bone to release calcium and lows the amount of calcium that the kidneys can reabsorb.

For kids aged 2 to 12, the amount of calcium compared to citrate (an acid found in citrus fruits) in their urine can be used to predict if they are likely to develop kidney stones. A calcium/citrate ratio bigger than 0.25 indicates a higher risk. Kids who have a condition called Vesicoureteral reflux, where urine flows backwards from the bladder towards the kidneys, also have a greater risk of having too much calcium in their urine.

Risk Factors and Frequency for Hypercalciuria

Hypercalciuria, or high levels of calcium in the urine, is found in roughly 5% to 10% of adults. Significantly, around one third of people who form calcium kidney stones have hypercalciuria. This condition also seems to run in families, with up to 40% of close relatives of people with hypercalciuria and recurrent kidney stones also having hypercalciuria.

In the United States, there are more than 30 million people with kidney stones, and 1.2 million new cases per year. Notably, one third of these cases reveal hypercalciuria when tested. The occurrence of hypercalciuria in patients with recurrent kidney stones could go up to 40% to 50%.

Hypercalciuria is found in 5% to 10% of adults.
About one third of all calcium stone formers have hypercalciuria.
Up to 40% of close relatives of patients with hypercalciuria and recurrent stones also have this condition.
There are more than 30 million kidney stone patients and 1.2 million new cases each year in the U.S.
One third of kidney stone cases show hypercalciuria when tested.
If a person has recurrent kidney stones, there is a 40% to 50% chance they have hypercalciuria.

Postmenopausal women with osteoporosis but without a history of kidney stones have a 20% likelihood of having hypercalciuria. Additionally, calcium phosphate stones are more common in women than in men. Remarkably, up to 40% of post-menopausal women who have had osteoporotic fractures but no history of kidney stones were found to have hypercalciuria.

Postmenopausal women with osteoporosis but no kidney stone history have a 20% risk of hypercalciuria.
Calcium phosphate stones are more common in women.
Up to 40% of post-menopausal women with osteoporotic fractures and no kidney stone history have hypercalciuria.

Lastly, in children, cases of urolithiasis (the process of forming stones in the kidney, bladder, and/or urinary tract) are on the rise, especially in the last 10-15 years. Hypercalciuria is the most common metabolic problem found in pediatric patients with nephrolithiasis (kidney stones). Interestingly, there is no obvious connection between kidney stones and obesity in children, unlike in adults. But there is a higher incidence of hypercalciuria in children with significant vesicoureteral reflux (a condition where urine flows backward from the bladder toward the kidneys) compared to control groups.

Urolithiasis cases in children have been increasing over the last 10-15 years.
Hypercalciuria is the most common metabolic issue found in children with kidney stones.
There is no clear link found between obesity and kidney stones in children, which differs from adults.
Hypercalciuria is more common in children with significant vesicoureteral reflux compared to others.

Signs and Symptoms of Hypercalciuria

Hypercalciuria is a medical condition where there is an excess amount of calcium in the urine. It is often hard to spot in adults as there are no specific signs. However, it may be suspected in people who have kidney stones made of calcium, nephrocalcinosis (a condition where there is too much calcium in the kidneys), hypercalcemia (high calcium levels in the blood), hyperparathyroidism (overactive parathyroid glands), urinary crystalluria (crystals in the urine), and weak or brittle bones.

Despite not having noticeable stone formation, hypercalciuria can still lead to blood in the urine. This is especially common in children and is thought to be caused by tiny calcium oxalate crystals and extremely small stones causing tissue damage that can’t be picked up with standard diagnostic methods.

Kids tend to show symptoms more often than adults. As such, pediatricians need to be highly vigilant for hypercalciuria. Symptoms in children may include:

Visible or microscopic blood in the urine
Urinary urgency (need to urinate immediately)
Painful urination
Bedwetting
Incontinence (loss of bladder control)
Pain in the pubic area and urethra
Abdominal or side pain even without kidney stones

Testing for Hypercalciuria

If you have symptoms suggesting hypercalciuria, which simply means too much calcium in your urine, your doctor will ask you to collect your urine over 24-hours to test its calcium content. This method is especially important for kids with kidney stones, adults with a high risk of developing kidney stones, patients with repeated kidney stone episodes, and anyone highly determined to prevent recurrent kidney stones. Testing a random urine sample isn’t as accurate, which is why the 24-hour collection is critical for diagnosing hypercalciuria.

In adults, a 24-hour urine test showing a calcium level of 250 mg or more could mean you have hypercalciuria. For children, the diagnosis can be based on a couple of different measurements – over 4 mg of calcium for each kg of body weight, a calcium level of more than 200 mg in a 24-hour urine sample, or a ratio of calcium to creatinine (another chemical the body excretes in urine) of more than 0.18. The doctor will usually choose the measurement that shows the most abnormal result and may adjust any treatment based on this.

If you’re an adult with hypercalciuria and your blood calcium levels are elevated or borderline, your doctor might suspect hyperparathyroidism. This condition can be confirmed by testing your blood for the presence of parathyroid hormone (PTH), which is produced by the parathyroid glands.

Lastly, your doctor could check your vitamin D levels to spot a condition known as renal phosphate leak. In this condition, both vitamin D and urine phosphate levels are high, but serum phosphate levels are low. If you have high vitamin D levels and don’t respond to the usual treatment with thiazide (a type of medication), this could mean you have renal phosphate leak hypercalciuria.

Treatment Options for Hypercalciuria

If your blood calcium levels are normal, which indicates that you don’t have an overactive parathyroid gland (a condition called hyperparathyroidism), your diet should not have too much or too little calcium. Too little calcium might make your body absorb more oxalate, a substance that can contribute to the formation of kidney stones. It’s important to follow a balanced diet that’s low in animal proteins and salt. If blood tests show high levels of calcium in your urine even after following this diet, medication may be needed.

One of the common medications for this condition is thiazides. These drugs help your kidneys keep more calcium in your body and reduce the amount of calcium in your urine by up to 50%. Thiazides work by promoting the absorption of calcium in your kidneys, while also helping your body get rid of excess sodium and water. However, you must also limit salt in your diet for these drugs to work. Too much salt in your diet can restrict the effects of thiazides.

Keep in mind that thiazides may lower the amount of potassium in your blood, increase uric acid levels, and reduce the amount of citrate in your urine. As a result, you may also need to take a potassium supplement, specifically potassium citrate, when taking thiazides.

If thiazides aren’t effective even after reducing dietary sodium and adjusting the dosage, the problem might be due to an overactive form of vitamin D. In this case, you may need different treatments such as orthophosphates, which can lower vitamin D levels, or a drug called ketoconazole, which can decrease your body’s vitamin D levels by about 30 to 40%.

Orthophosphates increase phosphate levels in your blood, helping to naturally reduce the activation of vitamin D and increase absorption of calcium in your kidneys. These medications can also reduce the amount of calcium in your urine. Though they can be paired with thiazides, orthophosphates are especially beneficial when thiazides haven’t worked or can’t be used.

In some instances, another type of medication called amiloride can be given along with thiazides. This drug can help your body absorb more calcium and keep your potassium levels stable. But you should be careful with taking potassium citrate and amiloride together as they can potentially increase the potassium levels in your blood to dangerously high levels.

Potassium citrate can increase the amount of citrate in your urine while decreasing the amount of calcium, which is beneficial in reducing conditions like hypercalciuria, where there’s too much calcium in your urine.

If you have hyperparathyroidism, the best treatment is generally surgery to remove the overactive parathyroid glands. However, drugs that mimic calcium (known as calcimimetics) can also be used when surgery isn’t possible.

In children, the main treatment for high calcium in urine is dietary changes. They should not have too little or too much calcium unless their intake exceeds the recommended daily amount. Vitamin D supplements should be avoided, and the amount of animal protein should be within the recommended daily limits. A three to six-month trial of these dietary changes is usually tried before considering thiazide medications.

Having too much calcium in your urine, or hypercalciuria, can be caused by a variety of things. Some of these factors are:

Sarcoidosis, a disease affecting the body’s organs with abnormal tissue growth
PTH-related peptide production, which is related to your parathyroid glands
Certain types of cancer
Kidney stones that aren’t made of calcium, such as ones composed of uric acid or cystine
Taking in an excessive amount of vitamin D

What to expect with Hypercalciuria

The health of your bones is largely determined during your childhood years – thus, having high levels of calcium in the urine, known as pediatric hypercalciuria, can lead to lower bone mass and potentially long-term health issues. A person usually reaches their maximum bone mass by the age of 20. However, it’s still unclear if having lower bone mass as a child could lead to bone loss (osteopenia) or severe bone loss disease (osteoporosis) in adulthood.

The outlook for your bone health depends on what specifically is causing the issue. Other health problems often related to this condition include kidney stones (nephrolithiasis) and bone fractures resulting from osteoporosis.

Frequently asked questions

Hypercalciuria is a condition characterized by high levels of calcium in the urine. It is often found in people who regularly form calcium kidney stones and can also contribute to weakened bones.

Hypercalciuria is found in 5% to 10% of adults.

The signs and symptoms of Hypercalciuria can vary depending on the age of the individual. In adults, it is often difficult to spot as there are no specific signs. However, there are certain conditions that may be suspected in adults with Hypercalciuria, including kidney stones made of calcium, nephrocalcinosis (excess calcium in the kidneys), hypercalcemia (high calcium levels in the blood), hyperparathyroidism (overactive parathyroid glands), urinary crystalluria (crystals in the urine), and weak or brittle bones. In children, Hypercalciuria tends to present with more noticeable symptoms. Pediatricians need to be highly vigilant for Hypercalciuria in children. The signs and symptoms of Hypercalciuria in children may include: - Visible or microscopic blood in the urine - Urinary urgency (need to urinate immediately) - Painful urination - Bedwetting - Incontinence (loss of bladder control) - Pain in the pubic area and urethra - Abdominal or side pain even without kidney stones It is important to note that even without noticeable stone formation, Hypercalciuria can still lead to blood in the urine, especially in children. This is thought to be caused by tiny calcium oxalate crystals and extremely small stones causing tissue damage that cannot be detected with standard diagnostic methods.

Hypercalciuria can be caused by various factors, including genetic changes affecting calcium reabsorption processes in the kidneys, certain health conditions (such as hyperparathyroidism, Addison disease, bone cancers, and overactive thyroid), excessive intake of vitamin D or calcium in the diet, certain genetic conditions, excess steroid use, and diseases related to the kidneys, bones, and immune system. Additionally, a diet high in salt or animal protein may contribute to hypercalciuria.

The conditions that a doctor needs to rule out when diagnosing Hypercalciuria are: - Sarcoidosis - PTH-related peptide production - Certain types of cancer - Kidney stones that aren't made of calcium - Taking in an excessive amount of vitamin D

The types of tests that a doctor would order to properly diagnose hypercalciuria include: - 24-hour urine test to measure calcium levels - Blood test to check for elevated or borderline blood calcium levels - Blood test to check for the presence of parathyroid hormone (PTH) to confirm hyperparathyroidism - Vitamin D level test to detect renal phosphate leak - Measurement of calcium to creatinine ratio in urine for children - Measurement of calcium level in a 24-hour urine sample for children These tests are important for accurately diagnosing hypercalciuria and determining the appropriate treatment plan.

Hypercalciuria can be treated through various methods. One approach is to follow a balanced diet that is low in animal proteins and salt. This can help reduce the amount of calcium in the urine. If dietary changes are not effective, medications such as thiazides can be prescribed. Thiazides help the kidneys retain more calcium and reduce the amount of calcium in the urine. Another option is to use orthophosphates, which increase phosphate levels in the blood and naturally reduce the activation of vitamin D, leading to increased calcium absorption in the kidneys. In some cases, amiloride may be given along with thiazides to help the body absorb more calcium and maintain stable potassium levels. Surgery to remove overactive parathyroid glands is also a treatment option for hypercalciuria.

When treating Hypercalciuria, there are several potential side effects to consider. These include: - Thiazides, which are commonly used medications, may lower the amount of potassium in the blood, increase uric acid levels, and reduce the amount of citrate in the urine. As a result, a potassium supplement, specifically potassium citrate, may be needed when taking thiazides. - Orthophosphates, another type of medication, can increase phosphate levels in the blood, which helps reduce the activation of vitamin D and increase calcium absorption in the kidneys. However, orthophosphates can also reduce the amount of calcium in the urine. - Amiloride, when given along with thiazides, can help the body absorb more calcium and keep potassium levels stable. However, caution should be taken when combining amiloride with potassium citrate, as it can potentially increase potassium levels in the blood to dangerously high levels.

The prognosis for Hypercalciuria depends on the specific cause of the condition. It is unclear if having lower bone mass as a child could lead to bone loss (osteopenia) or severe bone loss disease (osteoporosis) in adulthood. Other health problems often related to Hypercalciuria include kidney stones (nephrolithiasis) and bone fractures resulting from osteoporosis.

You should see a urologist or a nephrologist for Hypercalciuria.