What causes hypercalciuria?

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

When properly evaluated, 97% of hypercalciuric patients can be classified according to etiology. Causes of hypercalciuria that need to be considered include the following:

  • Hyperthyroidism
  • Renal tubular acidosis
  • Sarcoidosis and other granulomatous diseases
  • Vitamin D intoxication
  • Glucocorticoid excess
  • Paget disease
  • Albright tubular acidosis
  • Various paraneoplastic syndromes
  • Prolonged immobilization
  • Induced hypophosphatemic states
  • Multiple myeloma
  • Lymphoma
  • Leukemia
  • Metastatic tumors (especially to bone)
  • Addison disease
  • Milk-alkali syndrome

Wong and colleagues reported that hypercalciuria was present in 91.9% of subjects on deferasirox, an oral iron chelator used widely in the treatment of thalassemia major and other transfusion-dependent hemoglobinopathies but was not present in a control group taking an alternative iron chelator, deferoxamine. [17]

Mahyar et al reported a significantly higher frequency of hypercalciuria and hyperuricosuria in children with vesicoureteral reflux (VUR) than in a control group. These authors also observed a positive correlation between hypercalciuria and hyperuricosuria and severity of VUR (P < 0.05). [18]

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 1 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.


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