eMedicine Specialties > Pediatrics: General Medicine > Nephrology
Hypercalciuria
Updated: Jul 25, 2008
Introduction
Background
Hypercalciuria is defined by a 24-hour urinary calcium excretion more than 150 mg in an adult female, more than 200 mg in an adult male, or more than 4 mg/kg/d in a child who weighs less than 60 kg. In infants younger than 3 months, 5 mg/kg/d is considered the upper limit of normal for calcium excretion.
Hypercalciuria can be classified as idiopathic or secondary. Idiopathic hypercalciuria can be diagnosed when clinical, laboratory, and radiographic investigations fail to delineate an underlying cause. Secondary hypercalciuria occurs when a known process produces excessive urinary calcium. Elevated urinary calcium occurs by 3 primary mechanisms, as follows: (1) the filtered load of calcium is abnormally increased without an adequate compensatory increase in tubular calcium reabsorption, (2) the filtered calcium load is normal but tubular calcium reabsorption is reduced, or (3) the filtered load is increased and the reabsorbed load is reduced. A good screening test for hypercalciuria compares the ratio of urinary calcium to creatinine. To validate the screening test, an accurately timed urinalysis should be used to confirm any positive screens.
Pathophysiology
Urinary excretion of calcium is the result of the complex interplay of the GI tract, bone, and the kidney, which is regulated by multiple hormones. Hypercalciuria is believed to be a polygenic trait and is significantly influenced by diet.
Idiopathic hypercalciuria is the most common metabolic abnormality in patients with calcium kidney stones. Subjects with idiopathic hypercalciuria have a generalized increase in calcium turnover, which includes increased gut calcium absorption, decreased renal calcium reabsorption, and a tendency to lose calcium from bone. Despite the increase in intestinal calcium absorption, a negative calcium balance is commonly seen in balance studies, especially in patients on a low-calcium diet. The mediator of decreased renal calcium reabsorption is unclear; it is not associated with either an increase in filtered renal calcium or altered parathyroid hormone (PTH) levels.
An increased incidence of hypercalciuria is observed in first-degree relatives of individuals with idiopathic hypercalciuria, but it appears to be a complex polygenic trait with a large contribution from diet to expression of increased calcium excretion. Increased tissue vitamin D response may be responsible for manifestations of idiopathic hypercalciuria in at least some patients.1,2
Frequency
United States
Hypercalciuria occurs in as many as 10% of children.
International
Incidence varies, with rates of 3-7% in Eastern Europe. Incidence and prevalence data from nonindustrialized countries are lacking; however, calcium-containing urinary stones occur in children from all parts of the world.
Race
Idiopathic hypercalciuria has no ethnic, racial, or gender predominance among children in the United States. Secondary hypercalciuria occurs in a distribution consistent with the underlying etiology.
Sex
Idiopathic hypercalciuria occurs with equal frequency in boys and girls.
Age
Hypercalciuria can occur at any age, including newborns. The peak incidence of idiopathic hypercalciuria is in children aged 4-8 years. The age distribution of children with secondary hypercalciuria reflects that observed in the underlying etiology.
Clinical
History
In children with hypercalciuria, microcrystallization of calcium with urinary anions has been suggested to lead to injury of the uroepithelium. Consequently, when taking the history of the illness, attempt to identify symptoms relating to the urinary tract. Pay particular attention to the following items:
- Dysuria abdominal pain
- Irritability (infants)
- Urinary frequency
- Urinary urgency
- Change of urine appearance
- Colic
- Daytime incontinence
- Isolated or recurrent urinary tract infections (UTIs)
Some clinical manifestations are age dependent. For instance, irritability may be the only manifestation in infants, but a teenager may experience renal colic and hematuria.
Other important aspects of the history include the following:
- Past medical history
- Skeletal diseases (eg, osteoporosis, Paget disease) may produce hypercalciuria.
- Immobilization for various reasons (eg, postoperative, orthopedic injury, burns, intensive care, spinal cord injury, bone marrow transplants) can cause rapid bone remodeling and, hence, elevated calcium excretion. Fortunately, this is less common now after the introduction of early mobilization strategies and physical therapy.
- Nephrolithiasis is commonly associated with hypercalciuria. According to some studies, 30-50% of adults with kidney stones have idiopathic hypercalcuria.
- Hypercalciuria is not a rare finding among children with recurrent urinary tract infections.
- Malignancy is a common cause of hypercalcemia and hypercalciuria in hospitalized patients. It usually results from bone destruction, bone reabsorption, or humoral factors such as PTH-related protein.
- Human immunodeficiency virus (HIV) infection or its treatment may be associated with a higher risk of hypercalciuria in children.
- Medications: Certain medications, such as vitamin-D supplements and furosemide, may contribute to hypercalciuria. All loop diuretics decrease the tubular reabsorption of calcium.
- Diet and fluid intake
- Many dietary factors can alter urinary calcium excretion, including intake of sodium chloride, protein, glucose, sucrose, magnesium, and phosphate. An inverse relationship between phosphate intake and urinary calcium excretion is observed; thus, phosphate-restricted diets result in an increase in urinary calcium excretion. With all other dietary items mentioned above, a direct relationship between dietary intake and urinary calcium excretion is observed.
- The definition of hypercalciuria depends on a rate of excretion of calcium and, therefore, does not depend on the amount of water that is excreted with it. However, many children have more symptoms and are more likely to develop urinary stones with highly concentrated urine.
- Family history: Idiopathic hypercalciuria can run in families, as can other diseases that are associated with hypercalciuria. Approximately one half of persons with kidney stones and hypercalciuria have a first-degree relative who also has hypercalciuria.
Physical
Perform a thorough physical examination in all children with suspected or proven hypercalciuria. Quite often, no abnormalities are detected during the physical examination, and the diagnosis is made by history and laboratory evaluation. However, some children may have signs of hypercalcemia, including hypertension, dehydration, weakness, vomiting, and abdominal pain. Moreover, many children with secondary hypercalciuria may have physical examination findings consistent with the underlying disease process, such as those observed in hyperparathyroidism, malignancy, sarcoidosis, and adrenal insufficiency.
Causes
As the name implies, the cause of idiopathic hypercalciuria is not known. Several theories have been published, and some data supports certain aspects of these theories; however, these theories cannot yet be uniformly applied to a large patient population. Studies that examined metabolic balance have reported increased absorption of calcium from the intestine. In some instances, this process has been shown to be independent of vitamin D or a result of increased gut sensitivity to vitamin D.
In other patients with hypercalciuria, the proportion of calcium excreted into the urine is higher than normal, regardless of dietary intake of calcium. In fact, some patients have been found to have higher than normal urinary calcium despite lower than normal dietary intake, suggesting decreased renal tubular reabsorption.
This renal tubular leak is possibly a result of a mutational defect in one or more ion channels. Another proposed mechanism involves an imbalance of calcium deposition and reabsorption in bone that is independent of PTH or vitamin D. In addition, a combination of these factors may contribute to the high amounts of urinary calcium observed in patients with idiopathic hypercalciuria.
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References
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Further Reading
Keywords
hypercalciuria, idiopathic hypercalciuria, secondary hypercalciuria, kidney stones, renal stones, colic, osteoporosis, Paget disease, bone marrow transplantation, nephrolithiasis, human immunodeficiency virus, HIV infection, hyperparathyroidism, malignancy, sarcoidosis, adrenal insufficiency
