Appropriate and timely management of hyperkalemia is an important component of a nephrology practice. Hyperkalemia can result from increased K+ intake in the diet, impaired distribution between intracellular and extracellular spaces, and decreased kidney excretion. Risk factors associated with the development of hyperkalemia include older age, male sex, diabetes, underlying kidney disease, as well as intake of certain medications that affect the renin angiotensin aldosterone system (RAAS).
Prior to the advent of sodium zirconium cyclosilicate (SZC) and patiromer, only sodium polystyrene sulfonate (SPS) was available as a potassium exchange resin (1). Approved by the US Food and Drug Administration (FDA) in 1958, SPS has been mostly used in acute settings (Table 1). Although rare, the gastrointestinal (GI) toxicity of colonic necrosis was associated with high mortality if it happened.
Agents approved for managing hyperkalemia
Over the past several years, we have gained a much better understanding and newer tools with which to manage hyperkalemia, both in the acute and long-term scenarios. Although patiromer and SZC are advances, there are still limitations to consider.
The mechanism and onset of action make these agents quite useful in various clinical settings (2). Although SZC and patiromer have several advantages, including improved tolerability and an overall good safety profile, these agents can have a significant impact on financial costs with management of hyperkalemia.
In this pandemic era, the curtailment of patient exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by decreasing emergency room (ER) visits, reducing hospitalizations, and diminishing blood draws is a real benefit. Also, medical treatment of hyperkalemia and lessening of the burden on acute dialysis staff and available machines will help to prepare for any surge.
Financial data should be collected, and if the results are positive, actions should be taken to make these agents easily accessible, thereby potentially helping avoid ER visits, subsequent hospitalizations, and even the need for acute dialysis. Different practices should work on specific protocols to better manage hyperkalemia and include those protocols in quality improvement projects, i.e., regular assessment of the quality metrics, followed by appropriate action plans. This paradigm shift in the management of chronic hyperkalemia should open the doors for challenging endpoint studies in patients with kidney and cardiovascular diseases, where life-saving medications, such as RAAS inhibitors, mineralocorticoid receptor antagonists, and even beta-blockers, can be potentially titrated to the maximum dose. Another area of related interest may be how a more liberal diet affects the outcomes, nutritional status, and quality of life of patients (3). Many foods with health benefits (fruits and vegetables) also tend to be high in potassium.
There is a big push for home dialysis and urgent dialysis starts. A safe, effective, and well-tolerated potassium binder can make such a transition perhaps less challenging, particularly if hyperkalemia is one of the reasons driving the need for urgent-start kidney replacement therapy. This will give time for appropriate dialysis access placement, as well as evaluation and training, which will potentially translate into improved outcomes, including retention of patients on such dialytic modalities. The same applies to preemptive kidney transplantation, where a patient gets a transplant before going on dialysis. This is usually only possible if the patient has a potential living kidney donor, as the waiting time for a deceased kidney donation is quite protracted in most cases. However, at times, the living donor evaluation process may need to be delayed. A safe and effective K+ binder may help bridge the gap to a successful transplantation when the donor is ready.
In the future, cross-specialty training in hyperkalemia management is foreseeable. This should include trainees as well as clinical practitioners. Nephrology, cardiology, and diabetes specialists and primary care physicians should work collaboratively to optimize the medical management of patients, including keeping them on the medications and appropriately adjusted dosages as per kidney function.
The ultimate hope is that these novel oral K+ binders will help facilitate enhanced organ protection and at the same time, cause less hyperkalemia.
Dr. Lerma has received advisory board fees from AstraZeneca and research grants from ZS Pharma, Inc., which were involved with SZC studies.
Colbert GB, et al. Patiromer for the treatment of hyperkalemia. Expert Rev Clin Pharmacol 2020; 13:563−570. https://reference.medscape.com/medline/abstract/32511052
Palmer BF, et al. Clinical management of hyperkalemia [published online November 4, 2020]. Mayo Clin Proc doi: 10.1016/j.mayocp.2020.06.014
Palmer BF, Clegg DJ. Achieving the benefits of a high-potassium, paleolithic diet, without the toxicity. Mayo Clin Proc 2016; 91:496−508. doi: 10.1016/j.mayocp.2016.01.012