Urine Calcium

Calcium is one of the most abundant minerals in the human body. It has roles as the primary component of the transmembrane electrical gradient, in bone mineralization, and as an enzyme cofactor in the coagulation cascade. The body normally keeps serum and intracellular calcium levels under tight control through bone resorption and urinary excretion. 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: >350 mg/24-hour specimen

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

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

                   UCa(mg/100 ml GF) = [UCa (mg/dl) X Serum Creatinine (mg/dl)] / Urine Creatinine (mg/dl)

A value exceeding 0.16 mg/100 ml GF suggests an intense osteoclastic activity and bone resorption, and it is useful is evaluating renal stone disease and high turnover osteoporosis. ^[1]

 

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

• Males: 25-300 mg

• Females: 20-275 mg

The following conditions increase daily calcium excretion:

• Hyperparathyroidism

• Osteolytic bone metastases

• Myeloma

• Osteoporosis ^[2]

• Vitamin D and A intoxication ^[3]

• Distal renal tubular acidosis

• Idiopathic hypercalciuria

• Thyrotoxicosis

• Paget disease

• Fanconi syndrome

• Hepatolenticular degeneration

• Schistosomiasis

• Sarcoidosis

• Malignancy (breast, bladder)

• Osteitis deformans

• Immobilization

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

• Calcium salts

• Acetazolamide

• Cholestyramine

• Corticosteroids

• Dihydrotachysterol

• Initial diuretic use - Eg, furosemide

• Excessive litium (via inducing hyperparathyroidism) ^[3]

• Excesive administration of PTH

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). ^[4]

The following conditions decrease daily calcium excretion:

• Pseudohypoparathyroidism

• Hypoparathyroidism

• Rickets

• Osteomalacia

• Nephrotic syndrome ^[5]

• Acute glomerulonephritis

• Osteoblastic bone metastases

• Hypothyroidism

• Celiac disease

• Steatorrhea

• Hypocalciuric hypercalcemia (Familial hypocalciuric hypercalcemia) ^[6]

• Gitelman syndrome

• Bartter syndrome

Daily calcium 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

For further reading, please see the Medscape Reference topic Hypercalciuria.

Collection details are as follows:

• Container/tube: Plastic 10-mL urine tube (Supply T068) or a clean, plastic aliquot container with no metal cap or glued insert

• Specimen volume: 10 mL; mark the total 24-hour volume on the requisition and on the specimen container

• Specimen stability: Refrigerated (preferred), frozen, and ambient 7 days

Collection instructions are as follows:

• 24-hour collection, 24-hour volume required

• No preservative

• Refrigerate specimen within 4 hours of completion of 24-hour collection

• For multiple collections, the addition of preservative or application of temperature controls must occur within 4 hours of completion of the collection

It is recommended that urine specimens should be collected in containers containing low concentration of acids (most communly HCl) to avoid precipitation of calcium salts (eg, calcium oxalate). When such containers/acids are used, patients and laboratories should be carefull regarding their safety when handling and/or mixing the specimen. Also, the measured concentration should be corrected to acount for volume dilution by the acid solution. ^[1]

When specimens are collected without acid solutions, they must be acidified for 1 hour before testing and carefully mixed. ^[1]

Description

Calcium is one of the most abundant minerals in the human body. It has roles as the primary component of transmembrane electrical gradient, in bone mineralization, and as an enzyme cofactor in the coagulation cascade. The body normally keeps serum and intracellular calcium levels under tight control through bone resorption, removal from the kidneys, and excretion from the feces.

Indications/Applications

Evaluation of urine calcium excretion levels can aid in the differential diagnosis of recurrent renal calculi, as well as in the differentiation of familial hypocalciuric hypercalcemia from asymptomatic primary hyperparathyroidism.

Preferable specimens for urine calcium evaluation are 24-hour urine collections (rather than spot urine) using containers with an acid preservative. Creatinine should be determined on every specimen in order to be certain that the collection was adequate. Volume depletion may hinder urine calcium measurement.

In patients with hypoparathyroidism who are undergoing treatment with vitamin D and calcium supplementation, urine calcium concentration should be followed as an important variable. In this condition, a marked elevation in urine calcium concentration may be seen, as there would be no parathyroid hormone–associated increase in calcium reabsorption. Titrate the patient's dose of vitamin D so that urine calcium does not increase to greater than 350 mg/day. This usually involves a below-normal serum calcium level that is nonetheless high enough to prevent symptoms.

Knowing the patient's calcium intake is important in the differential diagnosis of idiopathic hypercalciuria; a great deal of variation in normal calcium excretion occurs in association with the dietary calcium level.

Attempting to use an absolute criterion in the diagnosis of hypercalciuria is problematic, because this criterion will be arbitrary, will probably result in the inclusion of some normal individuals in the diagnosis, and may cause some patients with abnormal calcium homeostasis or abnormal renal tubular calcium handling to be overlooked. Nonetheless, urine calcium excretion in most healthy men and women who consume an average of 600-1000 mg of elemental calcium daily is, respectively, less than 300 mg/day and less than 250 mg/day. The excretion values are higher in cases of idiopathic hypercalciuria.

Urine calcium excretion in most normal men and women with restricted calcium intake (400 mg/day) is, respectively, less than 250 mg/day and less than 200 mg/day. Urine calcium excretion is typically below 100 mg/day in patients with familial hypocalciuric hypercalcemia, despite the presence of hypercalcemia. ^{[7, 8]}

Considerations

Urine calcium excretion is normal in about one third of patients with hyperparathyroidism.

The ratio of urine calcium to urine creatinine (UCa/UCr ratio) can be used to demonstrate the extent of calcium excretion. As such, hypercalciuria is defined as a UCa/UCr ratio of more than 0.20 and more than 0.57 in men and women, respectively.

This test is not usually required to diagnose hyperparathyroidism (which can be diagnosed using serum calcium and parathyroid hormone values), but it can aid in the evaluation of renal stones. The test may also help in excluding the presence of familial hypocalciuric hypercalcemia in hypercalcemic patients.

For the diagnosis of hypercalciuria, good correlation exists between UCa/UCr ratios (in random, single-voided urine specimens) and 24-hour calcium excretion values.

With regard to familial hypocalciuric hypercalcemia, a study by McAllister et al indicated that evaluation of the urine UCa/UCr clearance ratio is more effective than a 24-hour urine calcium test in excluding the presence of this condition in patients prior to surgery for primary hyperparathyroidism. The investigators reported that at a cutoff value of 0.020 or below, the UCa/UCr ratio had positive and negative predictive values of 2.33% and 100%, respectively. The negative predictive value for familial hypocalciuric hypercalcemia associated with a low 24-hour urine calcium rate (< 2.5 mmol/L/24h) was 95.2%. ^[9]