Urine Calcium: Laboratory Measurement and Clinical Utility

Kevin F. Foley, PhD, DABCC; Lorenzo Boccuzzi, DO

Disclosures

Lab Med. 2010;41(11):683-686. 

In This Article

Abstract and Introduction

Abstract

Urine calcium measurement is a commonly ordered test in clinical laboratories. Unlike other urine markers, the utility of urine calcium is less clear to many laboratorians and physicians. Urine calcium can be used to assess parathyroid disease and familial hypocalciuric hypercalcemia (FHH). Although not predictive of stone formation, urine calcium is frequently elevated in patients with lithiasis. The primary clinical value of urine calcium measurement is to aid in the differential diagnoses of patients and direct optimal treatment options for patients with abnormal serum calcium.

Introduction

Because calcium is required for muscle contraction and nerve signaling, the serum concentration of calcium has obvious significance. Serum calcium also reflects parathyroid hormone (PTH) function and vitamin D status. Although the clinical importance of these 2 hormones and the resulting concentration of calcium in the serum is widely known, the role of urine calcium testing is not often discussed and is less obvious.

The average adult store of calcium is approximately 1–2 kg. The vast majority (99%) resides in the skeleton. Only a fraction of the stored calcium is present in extracellular fluid and available for use in the form of ionized calcium. Ionized calcium is tightly regulated by PTH. Adult calcium plasma concentrations are normally between 8.5–10.5 mg/dL (2.2–2.6 mmol/L). Most of this circulating calcium is bound to albumin. Because of this, changes in serum protein concentrations can affect total blood calcium concentrations. Calcium enters the extracellular fluid through absorption from the gut and resorption from bone. It is removed through secretion into the gastrointestinal tract and urine as well as losses in sweat and deposition in bone.[1]

The recommended dietary allowance (RDA) for calcium varies with age and, for adults, with gender. Recommended dietary allowance values for adults start at 1000 mg per day. Urine calcium levels will reflect dietary intake. In an average adult urine sample collected over 24 hours, 100–250 mg of calcium (15–20 mmol) is expected. For those on low-calcium diets 50–150 mg/day is expected, while those on a calcium-free diet will have 5–40 mg/day.[2] It is also important to note that calcium excretion (CE) is heavily influenced by sodium excretion. Low-sodium diets tend to decrease CE and vice versa.

Although a 24-hour collection is best, random urine calcium measurement can be performed and is expressed in relation to creatinine. A normal reference interval for the urine calcium (mg/dL):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 with time until approximately age 6. It is important to note this fact since most children will be falsely flagged as hypercalciuric using adult cut-offs.

Elevated urine calcium (>300 mg/24 hr) is often a sign of an overactive parathyroid gland. Parathyroid hormone is produced in response to serum calcium levels. Parathyroid calcium-sensing receptors (CASRs) stimulate increased PTH release in the presence of decreased serum calcium levels. Parathyroid hormone then works to increase serum calcium levels. The increases in serum calcium are achieved via increased renal tubule reabsorption of calcium and simultaneous decreases in phosphorus reabsorption. The serum concentration of phosphorus should be very similar to that of calcium since both are held in equilibrium to each other; as 1 goes up, the other tends to go down. Parathyroid hormone also causes reabsorption of calcium from bone as well as increased synthesis of 1,25-dihydroxy vitamin D, which stimulates calcium absorption from the gut. All of these actions lead to increased serum calcium. Hyperparathyroidism results in excessive uptake and increased concentrations of calcium in serum leading to hypercalcemia and hypophosphatemia. This is then reflected in the urine as hypercalciuria and hyperphosphaturia. Thus, urine calcium levels are often increased in the setting of hyperparathyroidism. However, one-third of hyperparathyroid patients have normal urine calcium, so this test is not reliable in differentiating or diagnosing hyperparathyroidism.[2]

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