Patiromer Reduces Potassium While Modestly Raising Calcium

In patients with chronic kidney disease, the risk of a potential small rise in calcium absorption should be weighed against the risk of hyperkalemia.
In patients with chronic kidney disease, the risk of a potential small rise in calcium absorption should be weighed against the risk of hyperkalemia.

New study findings suggest patiromer—a potassium-binding drug that uses calcium and other cations for exchange—effectively reduces gastrointestinal (GI) absorption of potassium and, to some degree, phosphate and sodium in healthy adults on controlled diets.

In 2 studies, David A. Bushinsky, MD, of the University of Rochester School of Medicine in New York, and colleagues examined urinary ion excretion as a proxy for GI absorption of potassium, sodium, magnesium, calcium, and phosphate. They studied healthy adults with normal kidney function instead of chronic kidney disease (CKD) patients because urinary ion excretion in CKD patients is delayed and may not reflect changes in intestinal absorption.

In a dose-finding study, 32 adults with no known medical conditions were randomly assigned to one of 4 patiromer treatments with a total daily dose of 2.5, 12.6, 25.2, or 50.4 g, taken orally with meals. The second dosing regimen study followed a crossover design during which 12 healthy adults received patiromer once, twice, or thrice daily for a total of 25.2 g, the maximum dose approved by the FDA. Diet was controlled in both studies for energy, macronutrient, and ion intake. Both studies lasted about 3 weeks.

Results of the dose-finding study showed that patiromer induced a dose-dependent reduction in urinary potassium and sodium, as well as magnesium. The 25.2 g dose decreased urinary potassium by a daily average of 1140 mg, urinary sodium by 225 mg, and urinary magnesium by 45 mg. Urinary calcium increased as dose increased with urinary phosphate decreasing in tandem. At the 25.2 g dose, daily urinary calcium increased by 73 mg and urinary phosphate decreased by 64 mg.

Results of the second study showed no differences in urinary potassium, sodium, and magnesium by dosing regimen. Urinary calcium, however, was significantly lower with a single daily dose of 25.2 g patiromer compared with the same total amount of drug dispensed in 3 doses. Urinary phosphate also decreased less with a single daily dose.

Along with demonstrating patiromer's effectiveness as a potassium binder, the findings suggest that the drug binds to some degree to both phosphate and sodium in the intestinal tract, thereby reducing phosphate absorption while not adding to dietary sodium intake.

Only a small amount of calcium (Ca) appeared to be available for absorption. “The data from these studies suggest that, by adding daily patiromer to a diet containing a moderate Ca load, the net elemental Ca available for absorption is within the recommended guidelines of the National Academies for the general population and below the total elemental Ca intake recommended for patients with CKD in the Kidney Disease Outcomes Quality Initiative guidelines,” Dr Bushinsky and colleagues wrote in the Clinical Journal of the American Society of Nephrology, published online ahead of print.

Renal impairment reduces urinary calcium excretion, so clinicians should weigh the risk of a potential small increase in calcium absorption against the risk of hyperkalemia in CKD patients, according to the investigators.  The risk for stone formation also needs to be assessed.

Although magnesium binding did not result in severe hypomagnesemia below 1.0 mg/dL, the investigators also recommended magnesium monitoring in treated patients, especially those receiving loop diuretics who are at risk for magnesium wasting.

No serious adverse events were reported in participants receiving patiromer. The most common side effects were GI.

Among the disclosures, the study authors acknowledged financial relationships with Relypsa, the makers of Veltassa (patiromer) along with other pharmaceutical companies.

 

Reference

1.   1. Bushinsky DA, Spiegel DM, Gross C, et al. Effect of Patiromer on Urinary Ion Excretion in Healthy Adults. CJASN. doi: 10.2215/CJN.01170216. [Epub ahead of print]

 

 

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