Pediatric Hypercalciuria Workup

As stated in the previous section, many different processes and disease states can produce overlapping symptoms and similar findings on urinalysis. A directed stepwise approach is important in the evaluation of a child with symptoms or a history compatible with hypercalciuria to avoid unnecessary expense, exposure to radiation, and patient discomfort. The first task is to document hypercalciuria. Looking for commonly associated urinary findings or problems that can produce similar symptoms is also easy and inexpensive. Consequently, the initial approach to any child with urgency, hematuria, or suspected hypercalciuria should include the following:

Urinalysis

A urinary tract infection is suggested by the presence of leukocyte esterase, WBCs, nitrite, or bacteria on microscopic examination findings. A urinalysis also can identify hematuria, a common but insensitive and nonspecific finding in children with hypercalciuria. The urine pH and the presence of crystals also may help identify possible clues or an explanation of the observed symptoms. Uric acid and calcium oxalate crystals are usually seen in acidic urine, whereas calcium phosphate and carbonate crystals are usually seen in alkaline urine. Similarly to hematuria, the presence of crystals or an abnormal pH is neither sensitive nor specific for hypercalciuria.

Urine calcium, creatinine, and uric acid

Not only does this study function as a reasonable screening test to document hypercalciuria, but it also reveals hyperuricosuria. The calcium-to-creatinine and uric acid–to-creatinine ratios should be calculated to determine whether or not abnormalities are present.

The normal calcium-to-creatinine ratio in children is less than 0.2. If the calculated ratio is higher than 0.2, repeat testing is indicated. One approach is to recheck the ratio at monthly intervals for 2 months. If the follow-up ratios are normal, then no additional testing for hypercalciuria is needed. On the other hand, if the ratio remains elevated, a timed 24-hour urine collection should be obtained and the calcium excretion calculated. The 24-hour calcium excretion test is the criterion standard for the diagnosis of hypercalciuria. If the calcium excretion is higher than 4 mg/kg/d, the diagnosis of hypercalciuria is confirmed and further evaluation is warranted.

If hyperuricosuria is detected, the appropriate evaluation for this condition should be initiated.

Follow-up testing

Once hypercalciuria has been diagnosed, several follow-up tests should be considered to search for an underlying etiology. If excess dietary intake or gut absorption of calcium is a concern, a simple way to verify or refute this notion is to temporarily limit dietary calcium intake and retest. The American Academy of Pediatrics (AAP) policy statement recommends that the daily calcium intake equal 800 mg in healthy children aged 4-8 years and 1300 mg in healthy children aged 9-18 years. If hypercalciuria is detected, place the child on a diet consisting of one-half the recommended daily allowance of calcium for 5 days and remeasure the urinary calcium excretion. If the calcium excretion normalizes, allow the child to resume a diet with an appropriate calcium content and reassess. If the urinary calcium excretion is still elevated despite reduced dietary intake, further testing is indicated.

Other laboratory tests

Other tests that are appropriate when trying to establish the cause of the hypercalciuria include serum vitamin D, vitamin A, phosphate, bicarbonate, creatinine, alkaline phosphatase, calcium, magnesium, pH, and parathyroid hormone levels. Freshly voided urine should be measured for bicarbonate and pH. A 24-hour urine collection also should be collected for measurement of calcium, phosphorus, sodium, and magnesium.

Urine calcium-to-osmolality ratio

In children with decreased muscle mass, urine calcium-to-osmolality ratio has been suggested as a more specific and sensitive screening test than calcium-to-creatinine ratio because of decreased urine creatinine excretion in those patients. A urine calcium-to-osmolality ratio (X 10) of less than 0.25 is considered to be suggestive of hypercalciuria.

Several imaging studies may be helpful in identifying underlying renal abnormalities or nephrolithiasis.

• A good place to start is with ultrasonography of the urinary tract. This reveals most major malformations, nephrocalcinosis, and many stones.
• Renal calyceal microlithiasis represents the presence of hyperechoic spots smaller than 3 mm in diameter in the renal calyces. In one study, renal calyceal microlithiasis was suggested to be present in as many as 85% of children with idiopathic hypercalciuria and did not seem to indicate an increased risk of lithiasis.^[5]
• If urinary tract stones are still a strong consideration despite normal ultrasound findings, a noncontrast helical CT scan is indicated. This has been shown to be a very sensitive and specific modality for identifying renal stones.
• Large proportions of stones are calcified and may be revealed using plain radiography of the abdomen, but this technique may miss a significant number of stones that are small or uncalcified.
• Intravenous pyelography (IVP) was widely used in the past to identify renal stones but is not used much in children anymore because of poorer image quality than CT scanning, larger radiation exposure, and potential toxicity of the contrast material. The cost is fairly equivocal.
• Follow-up imaging may be needed to assess new stone formation, progression, or resolution.
• Other radiographic studies may be indicated if metabolic bone disease is suspected or if a need to determine bone density exists. Plain radiography of the left hand or knees may be helpful to measure bone age. A dual energy x-ray absorptiometry (DEXA) scan can be used to determine bone density initially or follow bone density in children who require calcium-restricted diets. In children with idiopathic hypercalciuria, bone mineral density (BMD) measurements have consistently disclosed decreased Z-scores at the lumbar spine and, to a lesser extent, at the femoral neck.^[6]

• Unless renal stones form and are not spontaneously passed, procedures are not usually necessary in the evaluation of children with hypercalciuria.