Effect of Patiromer on Urinary Ion Excretion in Healthy Adults

Abstract

Background and objectives Patiromer is a nonabsorbed potassium-binding polymer that uses calcium as the counterexchange ion. The calcium released with potassium binding has the potential to be absorbed or bind phosphate. Because binding is not specific for potassium, patiromer can bind other cations. Here, we evaluate the effect of patiromer on urine ion excretion in healthy adults, which reflects gastrointestinal ion absorption.Design, setting, participants, & measurements We analyzed the effect of patiromer on urine potassium, sodium, magnesium, calcium, and phosphate in two studies. Healthy adults on controlled diets in a clinical research unit were given patiromer up to 50.4 g/d divided three times a day for 8 days (dose-finding study) or 25.2 g/d in a crossover design as daily or divided (two or three times a day) doses for 18 days (dosing regimen study). On the basis of 24-hour collections, urinary ion excretion during the baseline period (days 5-11) was compared with that during the treatment period (days 13-19; dose-finding study), and the last 4 days of each period were compared across regimens (dosing regimen study). ResultsIn the dose-finding study, patiromer induced a dose-dependent decrease in urine potassium, urine magnesium, and urine sodium (P,0.01 for each). Patiromer at 25.2 g/d decreased urine potassium (mean6SD) by 11406316 mg/d, urine magnesium by 4561 mg/d, and urine sodium by 2256145 mg/d. Urine calcium increased in a dose-dependent manner, and urine phosphate decreased in parallel (both P,0.01). Patiromer at 25.2 g/d increased urine calcium by 73623 mg/d and decreased urine phosphate by 64640 mg/d. Urine potassium, urine sodium, and urine magnesium were unaffected by dosing regimen, whereas the increase in urine calcium was significantly lower with daily compared with three times a day dosing (P=0.01). Urine phosphate also decreased less with daily compared with two or three times a day dosing (P,0.05).Conclusions In healthy adults, patiromer reduces urine potassium, urine sodium, urine magnesium, and urine phosphate, while modestly increasing urine calcium. Compared with divided dosing, administration of patiromer once daily provides equivalent reductions in urine potassium, urine sodium, and urine magnesium, with less effect on urine calcium and urine phosphate.

Patiromer Decreases Serum Potassium and Phosphate Levels in Patients on Hemodialysis

“…fig. 3) is in agreement with earlier studies in healthy volunteers showing that patiromer decreased gastrointestinal phosphate absorption as measured by a decrease in urine P on a controlled diet [17] . The reduction in serum P level seen in this study may be due to the gastrointestinal binding of P by the Ca released from patiromer, leading to less gastrointestinal P absorption.…”

“…This is consistent with the understanding that the main site of Ca-K exchange is in the colon where the efficiency of Ca absorption is minimal [18] . This is also in agreement with studies in healthy controls, where changes in urine calcium were used as a measure of intestinal ion absorption, which demonstrated that about 73 mg of calcium is absorbed from a daily dose of 25.2 g dose of patiromer [17] .…”

“…The finding that the levels of stool Na and Mg increased, support data that patiromer binds Na and Mg within the gastrointestinal tract as measured by a decrease in these ions in the urine excreted by healthy adults who are given patiromer [17] . The changes in stool Na are such that it suggests that patiromer may bind Na in the gastrointestinal tract as previously reported [17] .…”

Electrolyte and Acid-Base Disorders in Chronic Kidney Disease and End-Stage Kidney Failure

“…In healthy individuals, patiromer exhibits a dose-dependent lowering of urine K, Na, phosphate and Mg, consistent with an increased intestinal binding of these ions. It, on the contrary, increases urine calcium excretion, reflecting its calcium-releasing capacity [22]. It has an onset of action of 7 h. The OPAL-HK study [17] demonstrated the achievement of normokalemia after 4 weeks of patiromer treatment in 76% of hyperkalemic CKD stages 3 and 4 patients (n = 237) on RAAS inhibitors.…”

Evaluation of an individualized dose titration regimen of patiromer to prevent hyperkalaemia in patients with heart failure and chronic kidney disease

“…Patiromer uses calcium, rather than sodium, as the counterion for K + exchange 11. This avoids the potential for increases in sodium absorption and retention in patients with volume overload who may not tolerate even a small increase in sodium load, such as those with hypertension, CKD, and/or HF 18, 19. Patiromer has recently been shown to reduce serum aldosterone levels in patients with CKD and hyperkalaemia who are on RAASi 20.…”