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  • Treatment of primary hypercalciuria: Recent issues on treatment of genetic hypercalciuria

The amazing advances in molecular genetics have also in­volved hypercalciuria, and at least three candidate genes were shown to arbour mutations leading to altered calcium excretion. The chloride channel 5 (ClC-5), the calcium sensing receptor and the paracellin-1 are proteins encoded by corresponding genes, whose mutations causing either loss or gain of function, lead to hypercalciuric syndromes (Table II). Transfection or gene-disruption studies with these genes not only contribute to clarify mechanisms of the underlying diseases, but also help to understand the pathophysiology of idiopathic hypercalciurias. Recent reports have addressed the issue of treatment of ge­netic hypercalciurias, namely, in the course of Dent’s syndrome and familial hypocalcemic hypercalciuria. The mechanism leading to hypercalciuria in Dent’s syndromes is as yet not fully elucidated, in that both intestinal hyperab- sorption and renal leak could contribute. Chlorthalidone, but not amiloride, was shown to reduce both calcium excretion and calcium oxalate and calcium phosphate supersaturation in Dent’s syndrome, yielding similar results as in patients with id- iopathic hypercalciuria. These results led authors to con­clude that the hypocalciuric response to thiazides indicates that inactivation of the ClC-5 does not impair calcium transport in the distal convoluted tubule and that thiazides should be effec­tive in reducing the risk of kidney stone recurrence in these pa­tients. cialis professional canadian drugstore

Different approaches were tried in patients with CaR mutations with gain of function. These patients may present with hypocal- cemia of various severity, some of them presenting with major clinical signs of hypocalcemia. The classical treatment with ac­tive vitamin D derivatives, while relieving hypocalcemic symp­toms, induced significant increases in calcium excretion with an attendant risk of nephrocalcinosis. More recently, synthetic human PTH-(1-34) was shown to provide a safe and effective alternative to calcitriol therapy, able to maintain normal serum calcium levels without hypercalciuria. Similar encouraging results have been reported in two such patients by using hy- drochlorothiazide (1 mg/kg), which reduced urinary calcium ex­cretion and maintained serum calcium concentrations near the lower limit of normal, allowing the vitamin D doses to be re­duced, while alleviating symptoms. Finally, magnesium salts and thiazides were used to treat pa­tients with FHHNC (see Table II) caused by paracellin-1 muta­tions. While being of some efficacy to correct biochemical changes, treatment did not prevent, however, progression to chronic renal failure, which is a feature of this disease.

Table II – Genetic hypercalciuria.





Chloride channel 5 (ClC-5)



Dent’s syndrome and related disorders

Ca2+ Sensing* Receptor


Autosomal dominant

Familial hypocalcemic hypercalciuria (FHH)



Autosomal recessive

Familial hypomagnesiemic hypercalciuria and nephocalcinosis (FHHNC)

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