P1017A RANDOMIZED, PLACEBO-CONTROLLED MULTICENTER STUDY OF THE EFFECTS OF 12 WEEKS OF SODIUM ZIRCONIUM CYCLOSILICATE (SZC) ON ALBUMINURIA (UACR) IN PATIENTS WITH TYPE 2 DIABETES AND HYPERKALEMIA

Abstract Background and Aims Hyperkalemia is a frequent challenge in the treatment of type 2 diabetes and chronic kidney disease. It often leads to suboptimal dosing or discontinuation of renin-angiotensin (RAS) blockade, thus increasing the risk of renal disease progression. Furthermore, epidemiological findings indicate that high potassium levels impair the renoprotective effect of RAS blockade. We want to test whether adjunctive treatment with sodium zirconium cyclosilicate (SZC) a new treatment for hyperkalemia, improves the effect of standard RAS blocking treatment as measured by urinary albumin creatinine ratio (UACR) in individuals with type 2 diabetes. Method Randomized, double-blind placebo-controlled multicenter study with 2 sites in Denmark and 3 sites in Sweden. Individuals (n=100) with type 2 diabetes (age 18-85), persistent macroalbuminuria (UACR≥ 200 mg/g) on chronic RAS blocking treatment and documented hyperkalemia (plasma potassium ≥ 5.0 mmol/L at least once within 90 days of inclusion) will be enrolled in the study. Participants with plasma potassium >5.0 mmol/L at the last assessment before randomization will be randomized to receive SZC 10 g or placebo three times a day (tid) for 2 days followed by SZC 5g or placebo once a day (qd). Participants with serum potassium ≤ 5.0 mmol/L will be randomized to receive SZC qd or placebo qd.UACR will be measured in three consecutive morning spot urine collections at baseline and the end of study after 12 weeks of treatment with Lokelma or placebo. Results The primary outcome is change in geometric mean UACR from baseline to end of studySecondary outcomes include changes in estimated glomerular filtration rate (eGFR, calculated by CKD-EPI formula) and 24-h urinary sodium and potassium excretion.In an exploratory analysis the long-term effect of potassium reduction will be modelled using the PRE-SCORE risk calculator. In addition, changes in plasma aldosterone levels will be assessed, and safety will be monitored according to good clinical practice. Conclusion This study will test the concept of SZC as an add-on therapy to improve the renoprotective effect of standard RAS blocking treatment. This could provide future potential for keeping more individuals on optimal dosing of RAS blockade.