What is the role of orthophosphate therapy in the treatment of hypercalciuria?

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

In 1962, Howard et al first suggested the use of orthophosphate therapy (K-Phos Neutral, Neutra-Phos K, Uro-KP-Neutral) as a preventive treatment for kidney stones. [48] Stone cessation rates of more than 90% have been reported with this agent.

Orthophosphate therapy has been shown to decrease urinary calcium excretion by lowering serum vitamin D-3 levels (which reduces intestinal calcium absorption) and by increasing renal tubular calcium reabsorption. Orthophosphates may also have some intestinal calcium-binding capability, but the limited studies conducted on this issue have not confirmed this effect.

Overall, orthophosphates lower 24-hour urinary calcium excretion by about 50% in patents with absorptive hypercalciuria and by about 25% in patients with other hypercalciuric states. No apparent effect on PTH levels exists in healthy individuals. Uncontrolled studies have shown kidney stone remission rates of 75-91% in recurrent stone formers on long-term orthophosphate therapy.

Orthophosphates also increase urinary stone inhibitors such as citrate and, particularly, pyrophosphate. Many patients (40% in one series) have even noted a loss of stone mass while on orthophosphate therapy. Orthophosphates are particularly useful in cases of absorptive hypercalciuria type III (renal phosphate leak) and when thiazides cannot be used or are ineffective.

The use of orthophosphates with thiazides is extremely effective in controlling urinary calcium excretion and reducing new kidney stone formation rates, particularly in hypercalciuric calcium oxalate stone formers.

About 60% of all dietary phosphate is absorbed in the duodenum and jejunum; 65% percent of the absorbed phosphate is excreted by the kidneys, and the rest is eliminated through the intestinal tract by secretion in the ileum and colon.

Adverse effects of orthophosphates

Side effects of orthophosphate therapy include diarrhea, bloating, and gastrointestinal upset. These usually are worst during the first 2 weeks of therapy, after which they tend to diminish. The medication must be taken 3-4 times per day, which reduces patient compliance.

Do not administer to patients with struvite (magnesium ammonium phosphate) stones or to patients with renal failure, because they can develop soft-tissue calcifications. Use cautiously in patients with a history of predominantly calcium phosphate stones or in whom the urinary pH is consistently alkaline (which promotes calcium phosphate precipitation and stone formation). In addition, patients with a previous history of gastrointestinal problems generally do not tolerate orthophosphate therapy well.

Currently available orthophosphate preparations tend to be rapidly dissolving, which increases the gastrointestinal upset and diarrhea. A slow-release form of potassium phosphate (UroPhos-K) is currently awaiting United States Food and Drug Administration (FDA) approval. This new preparation uses a wax matrix to slow the release of phosphate, reducing its adverse effects. It contains no sodium and is designed to modify urinary pH to 7.0, which discourages the formation of calcium phosphate crystals and calculi.

In a randomized, double-blind study, patients with absorptive hypercalciuria type I who were administered the slow-release phosphate preparation had an average daily urinary calcium level of only 171 mg; controls averaged levels of 288 mg/day. [49] Urinary inhibitor levels of citrate and pyrophosphate were increased in the group treated with orthophosphate, and no gastrointestinal adverse effects were reported. [49]

Orthophosphate dosing

To be effective, orthophosphates must be taken at regular intervals and in sufficient amounts. The neutral salt tends to have fewer adverse effects and is more effective than other preparations. Optimal levels of neutral orthophosphate are 1-2.5 g/day. Orthophosphate preparations for calcium-stone formers should be sodium free.


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