New Agents in Treatment of Hyperkalemia: an Opportunity to Optimize Use of RAAS Inhibitors for Blood Pressure Control and Organ Protection in Patients with Chronic Kidney Disease

Abstract

Optimizing RAAS inhibition is an important therapeutic goal, particularly in chronic kidney disease. Different strategies have been investigated to achieve this goal, including inhibiting the pathway at multiple steps and using maximum or even supramaximal doses. Hyperkalemia is one of the most significant barriers to all of the strategies mentioned above. Up until the recent past, there have been limited therapeutic options available for the prevention and treatment of hyperkalemia in the long term. New promising agents to treat hyperkalemia in outpatient settings, namely, patiromer and sodium zirconium, may provide a solution. This article will review the benefits and risks of RAAS inhibitors, strategies to optimize their use, and the new hyperkalemia treatments that can lower the risk associated with RAAS inhibiting therapies.

Potassium Binders for Hyperkalemia in Chronic Kidney Disease—Diet, Renin-Angiotensin-Aldosterone System Inhibitor Therapy, and Hemodialysis

“…15,19,40 This section discusses the clinical implications of addressing the effects of hyperkalemia management on diet, RAAS inhibitor therapy, and hemodialysis and reviews research with new K þ -binding agents that may 41,42 However, in patients at risk for hyperkalemiadsuch as those who have late stages of CKDdhigh dietary K þ presents a clinical challenge. 19,42 Dietary K þ restriction (<3 g/d) is recommended in patients at risk for hyperkalemia but should be individualized because it can lead to patients not receiving the benefits of a heart-healthy diet [43][44][45] (Table 3). 44,46,47 Appropriate dietary counseling is important in patients with CKD with or at risk of hyperkalemia but can be challenging in clinical practice without dedicated resources.…”

Preventing and treating kidney disease in patients with type 2 diabetes

“…The risk will be particularly relevant in patients combining risks, typically the elderly treated by RAAS inhibitor and antiinflammatory agents and suffering from acute diarrhea. The risk of hyperkalemia is also dependent on the dose of ACE inhibitor or ARA II [74,75]. The risk profile of acute renal failure mirrors the risk profile of hyperkalemia and both conditions are frequently concomitant.…”

“…In patients with abnormally high potassium level, it seems unreasonable to start therapies blocking RAAS. In RENAAL, including T2DM patients with CKD, the mean potassium concentration at baseline was 4.6 mmol/L and losartan was associated with a mean increase of up to 0.3 mmol/l [76] However, more than considering a potassium concentration threshold to start or not RAAS blocking therapy, it seems very important to monitor potassium in high risk patients and applying preventive actions [74,75], including the use of potassium binders [77]. Also for safety reasons, the dual RAAS blockade, especially the combination of ARA II and ACE inhibitors, is not recommended.…”