What is the role of vitamin D in the etiology of hypercalciuria?

Updated: Jun 02, 2021
  • Author: Stephen W Leslie, MD, FACS; Chief Editor: Vecihi Batuman, MD, FASN  more...
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Many cases of absorptive hypercalciuria involve elevated vitamin-D levels. [8] Vitamin D increases small-bowel absorption of calcium and phosphate, enhances renal filtration, decreases PTH levels, and reduces renal tubular calcium absorption, which ultimately leads to hypercalciuria. An elevated vitamin-D level accounts for the finding of fasting hypercalciuria in some cases of absorptive hypercalciuria type I. About 30-40%, and possibly as many as 50%, of patients with absorptive hypercalciuria demonstrate abnormally elevated vitamin D3 levels.

It has been suggested that some patients have an exaggerated response to, affinity for, or sensitivity to normal levels of vitamin D and its metabolites. Activation of vitamin D3 takes place in the proximal renal convoluted tubule. This activation can be reduced by ketoconazole therapy.

Serum vitamin-D determinations can be helpful in determining the etiology of hypercalciuria in difficult or resistant cases, but these tests are probably are unnecessary in most hypercalciuric patients except as part of a research study or other standardized protocol.

Sarcoidosis and hypervitaminosis D

Sarcoidosis is a chronic disease that causes granulomas in various parts of the body but most often in the lungs. Although the exact cause is unknown, this condition is thought to arise from an exaggerated cellular immune response. The prevalence in the United States is about 1-4 cases per 10,000 population.

In some patients with sarcoidosis, 1,25-dihydroxyvitamin D is synthesized in an uncontrolled fashion by macrophages in the sarcoid granulomas. This produces a hypervitaminosis-D state with hypercalcemia and, frequently, hypercalciuria. Rarely, hypercalciuria is found without the hypercalcemia. This vitamin-D overproduction is not controlled by increased serum calcium, PTH, or phosphate administration.

Limiting sunlight exposure and reducing vitamin D ingestion are recommended. Glucocorticoid therapy usually controls the hypercalcemia and hypercalciuria. Primary hyperparathyroidism has been reported in some patients with sarcoidosis. [25]

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