This is a summary of a presentation I attended at the National Kidney Foundation Spring Clinical Meeting on 10 April 2025.

Speaker: Linda Fried

Objectives:

1. Review physiology and pathology of hyperkalemia
2. Describe effective dietary interventions that prioritise cardiorenal protection
3. Discuss newer potassium binders

Potassium Balance

98% of the potassium in the body is in the intracellular fluid.

Serum potassium is controlled by two processed:

1. External balance – intake and excretion
2. Internal balance

Mechanisms of potassium homeostasis:

• Sensing K intake in GI tract
• Sense extracellular potassium levels

K rick meals are identified in the intestine and pancreas which will increase insulin to move potassium into the cells.

Rise in ECF potassium increase potassium uptake into the muscles. Eventually potassium will be excreted by the kidneys.

External balance:

• Diet
• Salt substitutes
• Administration (potassiu supplements)

Excretion

• 90% renal
• Small amounts in skin and sweat
• GI tract

What promotes K excretion in the kidney?

• eGFR
• distal tubular flow rate
• Distal sodium delivery
• Aldosterone
• Non-resorbable anions

What causes hyperkalemia?

1. Excessive potassium intake
2. Decreased renal excretion related to:
   1. Renal insufficient
   1. Decreased distal tubular flow from volume depletion, CHF, cirrhosis
   1. Mineralocorticoid Deficiency
   1. Distal tubular dysfunction – commonly seen in diabetes and urinary retention

You need both factors to get hyperkalemia.  It is hard to eat so much potassium to get hyperkalemia if renal excretion is working well.

Medications that increase hyperkalemia risk

• NSAIDs
• RAASi
• MRA
• Potassium sparing diuretics
• Beta blockers
• Calcineurin inhibitors
• Heparin
• Trimethoprim

What is a normal serum potassium?

Normal potassium mean is around 4mmol/L. But as eGFR declines more patients will have higher potassium.

Who gets hyperkalemia?

People who have previously had hyperkalemia are more likely to get hyperkalemia again.  Recurrence rates are about 36%. Higher risk groups are older age, diabetes, lower eGFR, history of MI or CHF, use of RAASi. Lower risk groups are women, younger age, higher eGFR, use of diuretics.

What dictates how much potassium is removed by dialysis?

This is a factor of the dialysate bath and the serum potassium levels. Dialysis levels typically go down during the dialysis treatment and then rebound up after dialysis. However consider that the greater the change in the serum potassium during the dialysis session, the higher the risk of arrythmia during the dialysis session.

In dialysis patients higher risk of hyperkalemia:

• Longer time between dialysis session
• More common in younger patients
• Associated with mortality – lowest risk is 4.6-5.3mmol/L for dialysis patients

What are the risks of hyperkalemia?

Associated with increased risk of death, renal replacement therapy and adverse CVD outcomes.  But we don’t know if the relationship is direct or indirect (e.g. people who get hyperkalemia are more sick, stopped life saving medications, etc). However, there are some people who have EKG changes so significant that it can cause death.

And also consider that hypokalemia is also associated with increased mortality.   Though again it is hard to tease out if this is related to EKG changes or other patient characteristics.

In a study of people who were taking RAASi and had them stopped due to hyperkalemia, there was a higher mortality risk.

Summary:

• Potassium levels are managed by internal and external balance
• Incidence of hyperkalemia increases with lower eGFR, DM, CVD and RAASi
• Hyperkalemia is associated with increased mortality
• Discontinuation of RAASi is common with hyperkalemia, and is associated with mortality.

Can patients with CKD Eat Healthy and Avoid Hyperkalemia?

Speaker: Annabel Biruete PhD RD

Outline:

• Factors influencing development of hyperkalemia
• Relationship between dietary K intake and serum
• K restriction – should we restrict?
• Healthy dietary patterns and K in CKD
  Strategies to managing low K diet

What factors influence development of hyperkalemia?

• After a high K meal, some potassium is absorbed in the small intestine = defines post-prandial hyperkalemia
  • There is also potassium not absorbed, which will be excreted in the feces
• As kidney function declines, colonic potassium excretion increases
• Several factors impact how much potassium is taken up by the cell?
  • CHO rich meal stimulates insulin release which increase K uptake
  • However acidosis and muscle wasting may lead to decreased potassium uptake
  • Exercise increased K uptake by the cells
• Decreased kidney function or RAASi will decrease urinary potassium excretion

There is an assumption that dietary potassium intake drives serum potassium.  But observational studies suggest that this relationship is weak.  Several studies have reported no association with intake and serum levels.

(My aside – she didn’t discuss how potassium intake was assessed and why that matters in observation studies can be found in my previous posts here).

What foods are restricted in low potassium diets?

Many online resources recommend restricting foods without mention of portion sizes or cooking methods.  These classic low potassium diets lead to the opposite recommendations for a cardioprotective diet.

Key nutrient factors that impact potassium handling to consider in hyperkalemia management

Key modifiable factors of the diet include:

• Fibre – increase intake to reduce constipation and reduce the bio accessibility of potassium from foods
• CHO content of meals – insulin secretion helps increased cellular potassium intake
• Acid-base balance – fruits and vegetables help avoid extracellular K

Are plant-based diets better for CKD and hyperkalemia management?

Unfortunately, we do not have intervention studies including people who have hyperkalemia or have a high risk of hyperkalemia, so we don’t know if plant-based diets are safe. The speaker thinks that probably yes.

So here are the steps she proposes:

• Step 1: Try to avoid restrict lists and diets
• Step 2: Modulate potassium content of foods and meals
  • Limit portion size
  • Prepare foods using wet cooking methods (discard the water)
  • Avoid potassium additives in ultra-processed foods
• Step 3: Increase fibre intake
  • High fibre K foods likely are lower in bioaccessible K
  • Alkali effect
  • Viscous and bulking to enhance transit time
• Step 4: Provide culturally appropriate recommendations

Summary:

• Several factors other than food that impact the development of hyperkalemia
• Dietary patterns that promote cardiorenal health are possible
• Clinicians can use different modifications to lower potassium

Pharmalogical Management of Hyperkalemia

Presenter: Dr. Bruce Spinowitz MD

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 points – in KDIGO 2021 Clinical practice guidelines it is recommended to avoid stopping or lower RAASi for hyperkalemia but instead employ other strategies to treat hyperkalemia and maintain patients on these medications. As evidence suggests 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 sulphonate (SPS), commonly known as Kayexalate, was released in a time when drug studies only needed to demonstrate safety.  Current drugs require more robust data prior to release.  Originally SPS was released with a laxatives (often sorbitol), which made it unclear how this medication was working.  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.

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