Pharmalogical Management of Hyperkalemia

Presenter: Dr. Bruce Spinowitz MD

This is a summary of a presentation I attended at the National Kidney Foundation Spring Clinical Meeting on 10 April 2025. For a full list of presentations and summaries I attended, check out my other post here.

Objectives:

• Discuss properties of old and new potassium binders
• Review data on mechanisms
• Examine safety
• Demonstrate real-world data on these binders

How hyperkalemia impacts pharmalogical management of CKD

Key point: The KDIGO 2021 Clinical Practice Guidelines recommend avoiding the discontinuation or lowering of RAASi for hyperkalemia. Instead, KDIGO suggests employing other strategies to treat hyperkalemia while keeping patients on these medications, as evidence shows that down-titration or discontinuation is associated with increased mortality.

However real-world data suggests that clinicians are struggling with this recommendation and are decreasing the dose or discontinue these medications.

Key Characteristics of Old and New K Binders

Sodium polystyrene sulfonate (SPS), commonly known as Kayexalate, was released at a time when drug studies only needed to demonstrate safety. Today, current drugs require more robust data before release. Originally, SPS was released with a laxative (often sorbitol), making it unclear how the medication worked. However, later studies demonstrated that SPS worked even without the sorbitol.

Patiromer starts working within 1 week.  It can impact magnesium levels as well.

Sodium Zirconium Cyclosilicate (SZC) starts working with 1 hour.  Specific to potassium, so unlikely to have other mineral losses.

What is patiromer?

• Patiromer is a novel potassium binder
• It is a resin
• Not systemically absorbed but other drugs can bind to eat, so take 3 hours away from other medications
• Also binds magnesium
• Some GI side effects, though relatively mild

In a phase 2 trial of people with diabetes, on ACE or ARB with hyperkalemia, started on patiromer, this medication effectively reduced hyperkalemia. In phase 3 trials, once daily patiromer demonstrated effective serum potassium lowering within 1 week. After switching some patients to placebo, the potassium levels increased.

Real world trials since the phase 3 trials have also been published.  In patients with heart failure, with hyperkalemia and taking spironolactone +/- RAASi, the addition patiromer reduced and maintained serum potassium levels in normal range.

In patients with resistant HTN (requiring 3-4 classes of antihypertensives), CKD and being treated spironolactone at ideal dose (50mg), patiromer was able to prevent hyperkalemia better than people who were getting placebo.

Take Away: The addition of patiromer is helping high risk groups stay on guidelines recommended medications by preventing or managing hyperkalemia. 

What is SZC?

• A novel potassium binder
• Mechanism of action is the crystal shape selectively traps potassium
• Primary side effect is edema as this medication does include sodium

Phase 2 and 3 studies also demonstrated that SZC effectively achieved and maintained normokalemia.  Though interestingly this medication has demonstrated that the higher the serum potassium, the greater the correction of the serum levels were.

Real world studies have shown

1. That SZC used in patients with heart failure demonstrated that more patients were able to tolerate optimal therapy without hyperkalemia.
2. SZC used in people on dialysis and with hyperkalemia reported more patients started dialysis with normokalemia, even after their dialysis “weekend” – their longer number of days between dialysis sessions.