SuO019PATIROMER LOWERED SERUM POTASSIUM FOR UP TO 1 YEAR IN HYPERKALEMIC PATIENTS WITH DIABETES AND ADVANCED KIDNEY DISEASE ON RAAS INHIBITORS

Abstract

Introduction and Aims: Diabetes is a well‐recognized risk factor for chronic kidney disease (CKD) and the co‐occurrence of CKD in diabetes confers an even higher risk of poor cardiovascular outcomes. Guidelines recommend renin‐angiotensin‐aldosterone (RAAS) inhibitors to slow the progression of diabetic kidney disease (DKD), however patients with DKD are at high risk for hyperkalemia, which may limit or prevent RAAS inhibitor use. Currently available potassium (K)‐binding agents for hyperkalemia treatment are generally poorly tolerated, which may limit long‐term use. AMETHYST‐DN evaluated the novel agent patiromer, the active moiety of which is a nonabsorbed potassium (K+)‐binder, in a 1‐yr trial of patients with diabetes and CKD on RAAS inhibitors. In this post hoc subanalysis, we report the results of long‐term patiromer therapy in patients with advanced CKD (stages 4‐5). Methods: AMETHYST‐DN was a multicenter, open‐label trial of 306 patients with estimated GFR 15 to <60 mL/min/1.73m2, type 2 diabetes, hypertension and documented hyperkalemia (serum K+ >5.0 mEq/L) on RAAS inhibitors. Patients were randomized to patiromer starting doses by baseline serum K+: >5.0‐5.5 mEq/L (mild hyperkalemia), 4.2, 8.4 or 12.6 g BID; and >5.5‐<6.0 mEq/L (moderate hyperkalemia), 8.4, 12.6 or 16.8 g BID. Patiromer was titrated, if needed, to achieve and maintain serum K+ ≤5.0 mEq/L. A total of 74 patients had CKD stage 4‐5, 41 patients presenting with mild hyperkalemia and 33 with moderate hyperkalemia. Mean changes in serum K+ from baseline were analyzed at prespecified intervals during treatment and post‐treatment follow‐up. Results: Advanced CKD patients had diagnosed diabetes (mean, 14 yr) and median urine albumin‐to‐creatinine ratio of 632 mg/g at baseline. Patiromer induced significant (p<0.01) reductions in mean serum K+ in these patients at the first post‐baseline assessment, 48 hr after the first dose, from baseline means of 5.2 mEq/L (mild hyperkalemia) and 5.7 mEq/L (moderate hyperkalemia). Similar effects were observed across starting dose groups. In advanced CKD patients mean serum K+ was controlled (≤5.0 mEq/L) at 48 hr (mild hyperkalemia) and atWeek 1 (moderate hyperkalemia) and maintained for 52 weeks. Cessation of patiromer treatment led to a rise in mean serum K+. Of the randomized advanced CKD patients, 56% completed the trial (the most common reasons for early withdrawal were consent withdrawal [13.3%] and adverse event [9.3%]). Constipation was the most common gastrointestinal adverse event (9.5%, none severe; led to discontinuation in 1 [1.4%] patient). Six patients (8.1%) had serum K+ <3.5 mEq/L (none <3.0 mEq/L) and 3 (4.1%) had serumMg <1.2 mg/dL (none <1.0 mg/dL). Conclusions: Chronic treatment with patiromer in hyperkalemic patients with advanced DKD receiving RAAS inhibitors was well tolerated andmaintained serum potassium ≤5.0 mEq/L for up to 1 yr. Serum K+ monitoring may be required after patiromer discontinuation. (Figure Presented).