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

IMPORTANCEHyperkalemia 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/1.73m 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 MEASURESThe 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 < .001for 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 significant decreases in serum potassium level after 4 weeks of treatment, lasting through 52 weeks.