Revisiting RAAS blockade in CKD with newer potassium-binding drugs

Abstract

Among patients with proteinuric chronic kidney disease (CKD), current guideline recommendations mandate the use of agents blocking the renin angiotensin aldosterone system (RAAS) as first-line antihypertensive therapy based on randomized trials demonstrating that RAAS inhibitors are superior to other antihypertensive drug classes in slowing nephropathy progression to end-stage renal disease. However, the opportunities for adequate RAAS blockade in CKD are often limited, and an important impediment is the risk of hyperkalemia, especially when RAAS inhibitors are used in maximal doses or are combined. Accordingly, a large proportion of patients with proteinuric CKD may not have the anticipated renoprotective benefits since RAAS blockers are often discontinued due to incident hyperkalemia or are administered at suboptimal doses for fear of the development of hyperkalemia. Two newer potassium binders, patiromer and sodium zirconium cyclosilicate (ZS-9), have been shown to effectively and safely reduce serum potassium levels and maintain long-term normokalemia in CKD patients receiving background therapy with RAAS inhibitors. Whether these novel potassium-lowering therapies can overcome the barrier of hyperkalemia and enhance the tolerability of RAAS inhibitor use in proteinuric CKD awaits randomized trials.

Keywords: RAAS blockade; chronic kidney disease; hyperkalemia; patiromer; sodium zirconium cyclosilicate.

Figure 1. Chemical structure of patiromer and the calcium-sorbitol counter ion

Image reproduced with permission from Relypsa, Inc., VELTASSA® Prescribing Information 2016. Redwood City, CA

Figure 2. Structure of Sodium zirconium cyclosilicate

Pore detail with potassium ion (A), sodium ion (B), and calcium ion (C). Blue sphere indicates oxygen atoms; green spheres, silicon atoms; and red spheres, zirconium atoms. Reprinted from Stavros et al. with permission of the publisher. Copyright: © 2014 Stavros et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.