also see Hematuria

Furosemide therapy has been associated with the development of hypercalciuria, most commonly among infants who receive the drug for treatment of bronchopulmonary dysplasia. The first sign of hypercalciuria is usually microscopic hematuria with red blood cells (RBCs) in the urine. Hypercalciuria usually is asymptomatic, but occasionally may be severe enough to result in calcium stone formation and abdominal pain. Any patient who is receiving chronic furosemide or loop diuretic therapy, such as the infant described in the vignette, should be screened routinely for RBCs in the urine.

It is important to note that a urine dipstick test that is positive for "blood" is not always indicative of RBCs in the urine. Urine may appear red or brown due to the presence of hemoglobin, myoglobin, or porphyrins without containing RBCs. The presence of RBCs discriminates between blood originating from the urinary tract and other sources of discolored urine. Therefore, a urine sample that is positive for "blood" on dipstick must also contain RBCs to consider the diagnosis of hypercalciuria.

Screening the urine for calcium and creatinine is the best initial step in diagnosing hypercalciuria. A ratio of calcium to creatinine in a random urine sample of greater than 0.25 is suggestive of hypercalciuria, but it varies with age. Such a finding should be followed by a 24-hour collection of urine for calcium quantification. Urine calcium excretion greater than 4 mg/kg per day confirms the diagnosis. Further evaluation should include measurement of serum calcium and phosphate. If either of these values is abnormal, serum 25 hydroxyvitamin D, 1,25 dihydroxyvitamin D3, and parathyroid hormone levels also should be measured. As with any child who has persistent presence of RBCs in the urine, renal ultrasonography should be obtained.

Although the infant in the vignette developed hypercalciuria due to furosemide therapy, idiopathic hypercalciuria is more common. Other causes of hypercalciuria include Bartter syndrome, as a side effect of corticosteroid therapy, sarcoidosis, immobilization, vitamin D toxicity, and distal renal tubular acidosis.

Treatment options for hypercalciuria depend on the etiology. Because most cases are idiopathic, initial therapy involves aggressive hydration. Inadequate reduction of urine calcium excretion may result in either nephrocalcinosis or calcium stone formation. In these patients, hydrochlorothiazide therapy should be instituted. Calcium oxalate stones are the most common types of kidney stones in the United States. 

CHLA Board Review 2005
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