Revisiting RAAS blockade in CKD with newer potassium-binding drugs

Kidney Int. 2018 Feb;93(2):325-334. doi: 10.1016/j.kint.2017.08.038. Epub 2017 Dec 21.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Angiotensin II Type 1 Receptor Blockers / adverse effects
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Animals
  • Biomarkers / blood
  • Chelating Agents / adverse effects
  • Chelating Agents / therapeutic use*
  • Humans
  • Hyperkalemia / blood
  • Hyperkalemia / diagnosis
  • Hyperkalemia / drug therapy*
  • Hyperkalemia / etiology
  • Potassium / blood*
  • Renal Insufficiency, Chronic / blood
  • Renal Insufficiency, Chronic / diagnosis
  • Renal Insufficiency, Chronic / drug therapy*
  • Renal Insufficiency, Chronic / physiopathology
  • Renin-Angiotensin System / drug effects*
  • Risk Factors
  • Treatment Outcome


  • Angiotensin II Type 1 Receptor Blockers
  • Angiotensin-Converting Enzyme Inhibitors
  • Biomarkers
  • Chelating Agents
  • Potassium