Patiromer to Reduce Albuminuria Through Increased Renin Angiotensin Aldosterone System Inhibition in Patients With CKD-A Feasibility Trial

Abstract

IntroductionWe tested the feasibility of adding a potassium binder to enable increased RAASi and reduce albuminuria in patients with CKD. In a controlled trial design, a potassium binder was introduced exclusively in patients developing hyperkalaemia following intensified RAASi, thereby mirroring clinical decision-making. MethodsWe planned to include 140 patients aged 18-80 with eGFR 25-60 mL/min/1,73m2, albuminuria, and a history of hyperkalaemia to an open-label, randomized trial comparing treatment with or without patiromer alongside maximally tolerated RAASi. Patients were randomized only if developing a documented P-potassium >5.5 mmol/L during run-in with intensified RAASi (losartan/spironolactone). The primary endpoint was change in urine albumin creatinine ratio. ResultsScreening among 800,000 individuals with available laboratory results yielded just 317 candidates meeting major selection criteria during 18⅔ months, with 75 ultimately included. Among them, only 23 developed P-potassium >5.5 mmol/L, qualifying for randomization. Consequently, only 20 participants completed the study, falling short of the planned 98, precluding a significant effect on the primary outcome. Inclusion and randomization challenges stemmed from a limited pool of eligible patients for intensified RAASi at risk of hyperkalaemia, along with a lower-than-expected incidence of hyperkalaemia during run-in. ConclusionDespite extensive screening efforts, few eligible patients were identified, and fewer developed hyperkalaemia during run-in. Hence, a trial design limited to CKD patients at high hyperkalaemia risk and including a run-in phase appears unlikely to provide evidence for a potential renal benefit from additional use of potassium binders.