What is absorptive hypercalciuria?

Updated: Apr 23, 2019
  • Author: Stephen W Leslie, MD, FACS; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Answer

Absorptive hypercalciuria is by far the most common cause of excessive urinary calcium. About 50% of all calcium stone formers have some form of absorptive hypercalciuria, which is caused by an increase in the normal gastrointestinal absorption of calcium, overly aggressive vitamin-D supplementation, or excessive ingestion of calcium-containing foods (milk-alkali syndrome). Calcium absorption occurs mainly in the duodenum and normally represents only about 20% of the ingested dietary calcium load. [8]

Increased intestinal calcium absorption produces a corresponding increase in serum calcium levels. Typically, serum parathyroid hormone (PTH) is low or in the low-normal range in absorptive hypercalciuria, because the serum calcium level is generally high.

Mild or moderate absorptive hypercalciuria can usually be controlled solely with dietary measures, but medical therapy is required in severe and resistant cases.

Type I

Absorptive hypercalciuria type I is a relatively rare condition, generally characterized by elevated urinary calcium and calcium/creatinine levels except while fasting.

A variant of absorptive hypercalciuria type I exists in which fasting hypercalciuria can occur due to excess serum vitamin D-3. This vitamin D–dependent variant can be diagnosed with the finding of increased serum vitamin-D levels and with correction of the fasting hypercalciuria with a trial of ketoconazole therapy. (Ketoconazole is a potent P450 3A4 cytochrome inhibitor that reduces circulating vitamin D-3 levels by 30-40%.)

As many as 50% of all patients with absorptive hypercalciuria type I may have increased levels of vitamin D-3. Other causes of fasting hypercalciuria can be identified by elevated PTH levels (renal leak and resorptive hypercalciuria) or by increased urinary phosphate levels with hypophosphaturia (renal phosphate leak calciuria, also called absorptive hypercalciuria type III).

Absorptive hypercalciuria type I represents an extremely efficient intestinal calcium absorption mechanism. Bone density is usually normal, because abundant calcium is available for bone deposition, and PTH levels are normal or low. In some cases, however, the urinary calcium excretion is even greater than the amount absorbed, resulting in a net negative calcium balance and possible decrease in bone density, which is the opposite of what would be expected. Researchers think that this could be due to elevated serum vitamin-D levels or may be the result of an increased sensitivity to vitamin D and its metabolites.

Type II

This is a less severe form, and most common variety, of absorptive hypercalciuria. It usually responds to moderate dietary calcium restriction. Fasting hypercalciuria is not present in this disorder.

Type III

Absorptive hypercalciuria type III, also called renal phosphate leak hypercalciuria, is a vitamin D–dependent variant of absorptive hypercalciuria. This condition, a relatively uncommon cause of hypercalciuria, should be suspected in any patient with hypercalciuria who has a low serum phosphate level. A serum phosphate level of less than 2.9 mg/dL has been suggested as sufficient to raise the suspicion of renal phosphate leak hypercalciuria.

The etiology is an obligatory and uncontrolled loss of phosphate in the urine due to a renal defect, with a low ratio of tubular maximum reabsorption of phosphate to glomerular filtration rate. [9]  This produces hypophosphatemia, which stimulates the renal conversion of 25-hydroxyvitamin D to the much more active 1,25-dihydroxyvitamin D-3 (calcitriol, vitamin D-3). Vitamin D-3 increases intestinal phosphate absorption to correct the low serum phosphate levels. However, it also simultaneously increases intestinal calcium absorption. This extra calcium eventually is excreted in the urine. The diagnosis is confirmed by the following findings:

  • Low serum phosphate
  • Hypercalciuria
  • High urinary phosphate
  • High serum vitamin D-3
  • Normocalcemia and normal PTH levels

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