Pediatric Hypercalciuria Clinical Presentation

In children with hypercalciuria, microcrystallization of calcium with urinary anions has been suggested to lead to injury of the uroepithelium. Consequently, when taking the history of the illness, attempt to identify symptoms relating to the urinary tract. Pay particular attention to the following items:

• Dysuria abdominal pain
• Irritability (infants)
• Urinary frequency
• Urinary urgency
• Change of urine appearance
• Colic
• Daytime incontinence
• Isolated or recurrent urinary tract infections (UTIs)

Some clinical manifestations are age dependent. For instance, irritability may be the only manifestation in infants, but a teenager may experience renal colic and hematuria.

Other important aspects of the history include the following:

Past medical history

• Skeletal diseases (eg, osteoporosis, Paget disease) may produce hypercalciuria.
• Immobilization for various reasons (eg, postoperative, orthopedic injury, burns, intensive care, spinal cord injury, bone marrow transplants) can cause rapid bone remodeling and, hence, elevated calcium excretion. Fortunately, this is less common now after the introduction of early mobilization strategies and physical therapy.
• Nephrolithiasis is commonly associated with hypercalciuria. According to some studies, 30-50% of adults with kidney stones have idiopathic hypercalcuria.
• Hypercalciuria is not a rare finding among children with recurrent urinary tract infections.
• Malignancy is a common cause of hypercalcemia and hypercalciuria in hospitalized patients. It usually results from bone destruction, bone reabsorption, or humoral factors such as PTH-related protein.
• Human immunodeficiency virus (HIV) infection or its treatment may be associated with a higher risk of hypercalciuria in children.

Medications

Certain medications, such as vitamin-D supplements and furosemide, may contribute to hypercalciuria. All loop diuretics decrease the tubular reabsorption of calcium.

Diet and fluid intake

Many dietary factors can alter urinary calcium excretion, including intake of sodium chloride, protein, glucose, sucrose, magnesium, and phosphate. An inverse relationship between phosphate intake and urinary calcium excretion is observed; thus, phosphate-restricted diets result in an increase in urinary calcium excretion. With all other dietary items mentioned above, a direct relationship between dietary intake and urinary calcium excretion is observed.

The definition of hypercalciuria depends on a rate of excretion of calcium and, therefore, does not depend on the amount of water that is excreted with it. However, many children have more symptoms and are more likely to develop urinary stones with highly concentrated urine.

Family history

Idiopathic hypercalciuria can run in families, as can other diseases that are associated with hypercalciuria. Approximately one half of persons with kidney stones and hypercalciuria have a first-degree relative who also has hypercalciuria.

Perform a thorough physical examination in all children with suspected or proven hypercalciuria. Quite often, no abnormalities are detected during the physical examination, and the diagnosis is made by history and laboratory evaluation. However, some children may have signs of hypercalcemia, including hypertension, dehydration, weakness, vomiting, and abdominal pain. Moreover, many children with secondary hypercalciuria may have physical examination findings consistent with the underlying disease process, such as those observed in hyperparathyroidism, malignancy, sarcoidosis, and adrenal insufficiency.

As the name implies, the cause of idiopathic hypercalciuria is not known. Several theories have been published, and some data supports certain aspects of these theories; however, these theories cannot yet be uniformly applied to a large patient population. Studies that examined metabolic balance have reported increased absorption of calcium from the intestine. In some instances, this process has been shown to be independent of vitamin D or a result of increased gut sensitivity to vitamin D.

In other patients with hypercalciuria, the proportion of calcium excreted into the urine is higher than normal, regardless of dietary intake of calcium. In fact, some patients have been found to have higher than normal urinary calcium despite lower than normal dietary intake, suggesting decreased renal tubular reabsorption.

This renal tubular leak is possibly a result of a mutational defect in one or more ion channels. Another proposed mechanism involves an imbalance of calcium deposition and reabsorption in bone that is independent of PTH or vitamin D. In addition, a combination of these factors may contribute to the high amounts of urinary calcium observed in patients with idiopathic hypercalciuria.