Effect of Patiromer on Serum Potassium Level in Patients With Hyperkalemia and Diabetic Kidney Disease

Abstract

IMPORTANCE Hyperkalemia is a potentially life-threatening condition predominantly seen in patients treated with renin-angiotensin-aldosterone system (RAAS) inhibitors with stage 3 or greater chronic kidney disease (CKD) who may also have diabetes, heart failure, or both. OBJECTIVES To select starting doses for a phase 3 study and to evaluate the long-term safety and efficacy of a potassium-binding polymer, patiromer, in outpatients with hyperkalemia. DESIGN, SETTING, AND PARTICIPANTS Phase 2, multicenter, open-label, dose-ranging, randomized clinical trial (AMETHYST-DN), conducted at 48 sites in Europe from June 2011 to June 2013 evaluating patiromer in 306 outpatients with type 2 diabetes (estimated glomerular filtration rate, 15 to <60 mL/min/1.73 m 2 and serum potassium level >5.0 mEq/L). All patients received RAAS inhibitors prior to and during study treatment. INTERVENTIONS Patients were stratified by baseline serum potassium level into mild or moderate hyperkalemia groups and received 1 of 3 randomized starting doses of patiromer (4.2 g [n = 74], 8.4 g [n = 74], or 12.6 g [n = 74] twice daily [mild hyperkalemia] or 8.4 g [n = 26], 12.6 g [n = 28], or 16.8 g [n = 30] twice daily [moderate hyperkalemia]). Patiromer was titrated to achieve and maintain serum potassium level 5.0 mEq/L or lower. MAIN OUTCOMES AND MEASURES The primary efficacy end point was mean change in serum potassium level from baseline to week 4 or prior to initiation of dose titration. The primary safety end point was adverse events through 52 weeks. Secondary efficacy end points included mean change in serum potassium level through 52 weeks. RESULTS A total of 306 patients were randomized. The least squares mean reduction from baseline in serum potassium level at week 4 or time of first dose titration in patients with mild hyperkalemia was 0.35 (95% CI, 0.22-0.48) mEq/L for the 4.2 g twice daily starting-dose group, 0.51 (95% CI, 0.38-0.64) mEq/L for the 8.4 g twice daily starting-dose group, and 0.55 (95% CI, 0.42-0.68) mEq/L for the 12.6 g twice daily starting-dose group. In those with moderate hyperkalemia, the reduction was 0.87 (95% CI, 0.60-1.14) mEq/L for the 8.4 g twice daily starting-dose group, 0.97 (95% CI, 0.70-1.23) mEq/L for the 12.6 g twice daily starting-dose group, and 0.92 (95% CI, 0.67-1.17) mEq/L for the 16.8 g twice daily starting-dose group (P < .001 for all changes vs baseline by hyperkalemia starting-dose groups within strata). From week 4 through week 52, statistically significant mean decreases in serum potassium levels were observed at each monthly point in patients with mild and moderate hyperkalemia. Over the 52 weeks, hypomagnesemia (7.2%) was the most common treatment-related adverse event, mild to moderate constipation (6.3%) was the most common gastrointestinal adverse event, and hypokalemia (<3.5 mEq/L) occurred in 5.6% of patients. CONCLUSIONS AND RELEVANCE Among patients with hyperkalemia and diabetic kidney disease, patiromer starting doses of 4.2 to 16.8 g twice daily resulted in statistically signific...

Effect of Patiromer on Urinary Ion Excretion in Healthy Adults

“…The magnitude of the decrease in presumed GI P absorption on the 25.2-g/d dose is within the range reported in patients with CKD given intestinal P binders, and it is similar to that achieved experimentally in vivo with 1000 mg elemental Ca in the form of Ca acetate (12,22). Because many individuals needing treatment for hyperkalemia are also receiving loop diuretics, a known cause for urinary Mg wasting (23,24), attention should be paid to the serum Mg in patiromertreated patients.…”

“…Although the magnitude of the reduction was relatively small, especially in the sensitivity analyses (80-150 mg), compared with dietary Na intake, patiromer does not add to dietary Na intake in contrast to other K binders in the United States that use Na as a counterexchange ion (2,12,13).…”

Focus on Hyperkalemia Management: Expert Consensus and Economic Impacts

“…25 Patiromer may present a better tolerability and safety option for these patients; however, neither SPS or patiromer are indicated for the management of emergent The 2 main clinical trials that contributed to the approval of patiromer were OPAL-HK and AMETHYST-DN. 32,33 The multinational, single-blind, 2-phase OPAL-HK study evaluated the efficacy of patiromer in patients with CKD who were receiving RAAS inhibitors. 32 In phase 1, all participants received a starting dose of patiromer of 8.4 grams or 16.8 grams daily in 2 divided doses, depending on the severity of hyperkalemia, at baseline for 4 weeks.…”

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

“…It is approved for the treatment of hyperkalaemia in the USA and in Europe 10, 11, 12. Patiromer has been shown to reduce serum K + in hyperkalaemic patients with CKD with or without other co‐morbidities, such as HF, diabetes mellitus, and/or hypertension 13, 14, 15. Patiromer has also been demonstrated in a randomized, double‐blind, placebo‐controlled study to prevent hyperkalaemia in normokalaemic patients with HF with or without CKD who were initiated on spironolactone 16.…”