Calcium Urine
The average adult has between 1 and 2 kg of total body calcium. Most of this calcium resides in bone. Only 1% of calcium is present in extracellular fluid. Most circulating calcium is bound to albumin. Calcium enters the extracellular fluid through absorption from the gut and resorption from bone. Calcium is cleared by secretion into the gastrointestinal and urinary tracts as well as by sweating and bone deposition.
Urine calcium levels vary with dietary intake. A 24 hour urine sample collected from an average healthy adult contains between 100 and 250 mg of calcium (15–20 mmol). Individuals adhering to a low calcium diet excrete between 50 and 150 mg per day, while individuals following a strict calcium free diet can have urine concentrations as low as 5 to 40 mg per day.
Measurement of urine calcium is useful in the differential diagnosis of patients with abnormal plasma calcium levels. Any disease that increases plasma calcium concentration can result in elevated urine calcium, which is defined as a concentration greater than 350 mg per 24 hours. The most common causes are hyperparathyroidism, familial hypocalciuric hypercalcemia, multiple myeloma, osteolytic neoplasms, osteoporosis, vitamin D overdose, renal tubular acidosis, hyperthyroidism, Paget's disease, and sarcoidosis. Although not predictive of stone formation, urine calcium is frequently elevated in patients with nephrolithiasis.
Familial hypocalciuric hypercalcemia (FHH) is typically a benign disease that does not require treatment. It is important to distinguish it from primary hyperparathyroidism which requires surgical intervention to prevent the long term complications of hypercalcemia. Guidelines suggest that a calcium creatinine clearance ratio (CCCR) of less than 0.010 is consistent with FHH, whereas a CCCR greater than 0.020 is highly suspicious of hyperparathyroidism. One study revealed that a CCCR cutoff of 0.020 captured 98% of patients with FHH but also included 35% of patients with primary hyperparathyroidism (Clin Endocrinol 2008;69:713–720). CCCR might be useful as an initial screening test for FHH, followed by CASR gene analysis for patients with a CCCR of less than 0.020.
Drugs containing calcium, such as some antacids, and calcium supplements can directly elevate urine calcium. Spironolactone increases urine calcium because it is given as a calcium salt and decreases tubular reabsorption of calcium. Androgens, growth hormone, acetazolamide and corticosteroids also increase calcium excretion. Low-sodium diets tend to decrease calcium excretion and vice versa.
Decreased urine calcium is seen in hypoparathyroidism, pseudohypoparathyroidism, rickets, hypothyroidism, steatorrhea, and nephrosis. Another cause of low urine calcium is familial hypocalciuric hypercalcemia. Some drugs can decrease urine calcium concentration including thiazide diuretics, benzothiadiazide diuretics, and estrogen. Apparent hypocalciuria is often due to incomplete collection of a 24-hour specimen.
Urine calcium concentration can be measured in a 24 hour urine collection or a random urine sample. Random urine calcium concentration is best expressed as the calcium to creatinine ratio. Some nephrologists prefer to calculate the calcium/creatinine clearance ratio (CCCR), which is also known as the fractional excretion of calcium. A fasting urine sample may also be useful in diagnosing calcium overdose from antacids or supplements. If a 2-hour urine collection is obtained after a 14-hour fast, the urine calcium:creatinine ratio should be less than 0.15.
The reference range for calcium in a 24 hour urine collection is less than 350 mg per day. A normal reference interval for the urine calcium (mg/dL) to urine creatinine (mg/dL) ratio is <0.14. Values exceeding 0.20 are found in patients with hypercalciuria. In children, the calcium/creatinine ratio decreases steadily until approximately age 6. If adult reference ranges are used for younger children their results will be falsely flagged as hypercalciuric.
