New Therapies for Hyperkalemia

Silvia J. Leon; Oksana Harasemiw; Navdeep Tangri


Curr Opin Nephrol Hypertens. 2019;28(3):238-244. 

In This Article

Conclusion and Future Perspectives

Hyperkalemia is one of the most commonly occurring electrolyte disorders in clinical practice, and is a serious, potentially fatal disorder if left untreated. Despite this, the incidence of hyperkalemia is increasing, secondary to the increase of patients with chronic conditions such as CKD, heart failure and diabetes, who are commonly treated with RAAS inhibitors, which are known to increase the risk of hyperkalemia. To mitigate this risk, a significant proportion of patients who would otherwise benefit from RAAS inhibitors either use this treatment at lower doses than recommended, or have altogether discontinued the medication secondary to hyperkalemia events. This is due to a lack of current treatment options for the concomitant chronic management of hyperkalemia, which in turn highlights the need for safer and more effective treatment alternatives. Two treatment options – patiromer and ZS-9 – are the first therapy options approved by the FDA for the management of hyperkalemia in the last 50 years.

Patiromer has been demonstrated to safely decrease serum potassium levels in patients with CKD and heart failure for short-intermediate-term treatment, as well as significantly reduce serum potassium levels in patients with hyperkalemia, or who are at high risk of developing the disorder, while also allowing patients to continue concomitantly receiving RAAS inhibitor therapy. Furthermore, ZS-9 has also demonstrated to have a favorable safety and tolerability profile in short duration trials. Due to its fast acting nature (onset within 1 h), it has the potential to be used for the management of acute hyperkalemia; however, further randomized trials are needed. More studies with both drugs are currently needed to evaluate the efficacy and safety of long-term treatment, as well as with study populations that include patients with CKD stages 4–5, end-stage renal disease (ESRD) and heart failure NYHA class III or IV.

New medications for the management of hyperkalemia are changing the management of this potentially fatal electrolyte disorder. To better understand the effectiveness and potential impact of these emerging drugs, it is important to understand the burden (incidence) of acute hyperkalemia in the general population, as well as amongst patients with known risk factors for hyperkalemia. In addition, information on the treatment patterns and clinical outcomes associated with hyperkalemia, in acute and chronic settings, is lacking and represents a significant knowledge gap. To date, no studies have evaluated whether therapy with RAAS inhibitors after an episode of hyperkalemia provides better outcomes, compared with the altogether discontinuation in patients with CKD and heart failure. Future studies addressing this gap are urgently needed.