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  • Treatment of primary hypercalciuria: Neutral potassium phosphate

An association between hypercalciuria and renal phosphate leak was first described by Bordier et al., who speculated that a primary defect of phosphate reabsorption at the proximal renal tubule could be responsible for hypophosphatemia, acti­vation of the renal 1 a-25(OH)2 vitamin D3 hydroxylase and par­tial inhibition of PTH secretion. The associated hypercalciuria would ensue from both increased intestinal absorption and de­creased tubular resorption of calcium. That this subtype of hy- percalciuria can be of clinical significance was confirmed by a recent report in which 19% of 207 stone formers had a TmPi of less than 0.63 mmol versus 5% of controls; daily calcium ex­cretion was higher in stone formers, more so if they had re­duced TmPi. It was also suggested that this hypothetical tubular defect could involve the type IIa Na+-phosphate co- transporter through mutations of the encoding gene Npt2. In fact, knock-out mice for the Npt2 gene [Npt2(-/-)] exhibited in­creased urinary Pi excretion, hypophosphatemia, elevation in 1,25-(OH)2 vitamin D, hypercalcemia, hypercalciuria and low PTH. Partially deficient mice [Npt2(+/-)] had similar though milder changes. It was suggested these features be typical of patients with hereditary hypophosphatemic rickets with hypercalciuria (HHRH), and that patients with phosphate leak hypercalciuria could have heterozigous mutations of the Npt2 gene. canadian- online canadian pharmacy

However, others have denied that Npt2 mu­tations could be responsible for both diseases. Phosphate supplementation, as neutral slow-release potassi­um phosphate, was given to patients with absorptive hypercal­ciuria. In a short-term study daily dosages corresponding to 40 mmoles of phosphate and 63.5 mmoles of potassium de­creased 24-hr and fasting urinary calcium by 40% and 43%, re­spectively. These marked changes were not simply attrib­utable to a decrease in intestinal absorption of calcium, which only fell by 6%, but were associated to a clear-cut decrease in bone resorption, as suggested by the significant decline in markers of bone turn over. These effects are consistent with the aforementioned contribution of bone resorption to the phos­phate-depletion induced hypercalciuria. The efficacy of phosphate supplementation to restore mineral metabolism are still debatable since, in the presence of renal leak, an increase in phosphate disposal could result in phosphaturia. In mice Npt2 (-/-) phosphate supplementation did not prevent hyper­calciuria and renal calcification, unless associated to ^-hy­droxylase gene ablation. If this also applied to humans, treatment of phosphate leak should not only include phosphate supplies but also inhibition of calcitriol synthesis.

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