Today, I review, link to, and excerpt from The Curbsiders‘ “#537 Hyperkalemia and Hypokalemia”.*

*Achi SS, Topf J, Williams PN, Watto MF. “#537 Hyperkalemia and Hypokalemia”. The Curbsiders Internal Medicine Podcast. thecurbsiders.com/category/curbsiders-podcast August 24, 2026.

Treatment of Hyperkalemia

Treatment of Hypokalemia

All that follows is from #537.

Transcript available via YouTube

I’m Going Bananas for This One!

Learn how to formulate a framework while dealing with potassium disorders in patients with varying levels of kidney disease.We’re joined by Dr Joel Topf, (@kidney_boy) to explore how to navigate potassium disorders, develop etiology frameworks, and treat these patients.

Claim CME for this episode at curbsiders.vcuhealth.org!

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Show Segments

• Intro
• Rapid fire questions/Picks of the Week
• Case 1: Hyperkalemia
• How to Approach Patients with Hyperkalemia
• Treatment Options for Hyperkalemia
• Case 2: Hypokalemia
• How to Approach Patients With Hypokalemia
• Treatment Options for Hypokalemia
• Case 3: Hyperkalemia in ESKD patients
• How To Approach the Management in ESKD patients
• Take Home Points
• Outro

Disclosures

Dr. Topf reports the following conflicts of interests: Advisor-Travere Therapeutics, Advisor-Otsuka, Advisor-Vera Therapeutics, Advisor-Novartis, Advisor-Vertex Therapeutics

The Curbsiders report no relevant financial disclosures.

Hyperkalemia and Hypokalemia Pearls

1. In a case of hyperkalemia, the first step is to rule out any cause of pseudohyperkalemia: such as hemolyzed samples
2. Hyperglycemia can cause hyperkalemia due to solute drag; if the sugars can be controlled, then that will aid in the control of hyperkalemia.
3. Medications can also lead to hyperkalemia so it’s important to do a thorough medication check.
4. The potassium switch manages high potassium through inactivation of a sodium-chloride transporter, causing a thiazide-like effect of distal sodium delivery and increased excretion of sodium and potassium
5. Even in dialysis patients who have hyperkalemia, there are roles for potassium binders
6. Proton pump inhibitors often cause hypomagnesemia and related hypokalemia; with repletion of magnesium, the potassium should improve.

TLS = Tumor Lysis Syndrome

Hyperkalemia and Hypokalemia-Show Notes

Hyperkalemia

How To Approach/How to Build a Framework

Hyperkalemia’s incidence in the general population is around less than 2% however in those with conditions such as chronic kidney disease, diabetes, or medications the incidence can increase up to 40-50% (Ellis 2024). These risk factors, along with metabolic acidosis, can predispose one to have hyperkalemia.  So how do we tackle the case of hyperkalemia that we see in labwork? Dr. Topf mentions the first step is to look and see if it is a case of pseudohyperkalemia. One way is to check if the sample is hemolyzed-which is usually marked on the lab results tab. Reasons for hemolyzed sample include: tight clenching of the fist, prolonged period of time that the tourniquet is applied, excess fist pumping prior to drawing the sample, or if there is a traumatic venipuncture (Asirvatham 2013). Cold temperatures have also been associated with pseudohyperkalemia (Afrin 2026, Rampul 2019).

Hyperglycemia, especially cases of severe hyperglycemia, can lead to hyperkalemia by way of a concept called solute drag.  Solute drag is a process where there is a rise in the extracellular compartment glucose due to hyperglycemia and it pulls the water from the intracellular compartment into the extracellular compartment, which thereby drags the potassium into the extracellular compartment leading to hyperkalemia (Ford 2026). Once the glucose is controlled the potassium will be controlled.

Dr. Topf likes to break down etiologies of hyperkalemia and even hypokalemia with the framework of intake, distribution, and excretion.

Intake

Dietary intake is rarely the primary driver of hyperkalemia, particularly in normal kidney function. (Joshi 2023). In general, the body has the ability to control and adjust its milieu in response to diet. In terms of the diet, not all foods will yield the same potassium effects. In addition, per Dr. Topf the electrolyte rich drinks don’t have much potassium content.

There are certain formulations of potassium and certain foods that are more bioavailable. Potassium switch occurs in the kidney to protect from hyperkalemia, and high-potassium diets may be helpful in hypertension (Sriperumbuduri 2024). The concept of potassium switch is in a setting where the potassium load is high, a thiazide-sensitive Na/Cl reabsorption in the distal convoluted tubule will inactivate, causing a thiazide-like effect, i.e.  more distal delivery of sodium past the distal convoluted tubule, and more sodium and potassium excretion. (Welling 2026). Mineral potassium is found in salt substitutes. The SSaSS Trial in China demonstrated less stroke, cardiovascular disease, and death in those replacing sodium chloride with potassium chloride(Neal 2021).

Studies have been done which show that salt substitutes which take the sodium chloride part of regular salt and replace it with potassium chloride which aids in blood pressure control as well in addition have more potassium bioavailable properties (Neal 2021).

Dr. Topf also emphasizes to patients the importance of a fiber rich diet. Fiber intake aids with colonic excretion of potassium especially as the stages of CKD advance (Narasaki 2026).

Distribution

Distribution of potassium is the second bucket that we should focus on when trying to identify the etiology of hyperkalemia. Potassium is largely an intracellular ion, and any pathology causing potassium to shift from intracellular to extracellularly falls into the distribution bucket.

Tumor lysis syndrome, rhabdomyolysis, periodic paralysis, hemolysis are some examples where the patients are sick and there is a precipitating cause of the hyperkalemia. Metabolic acidosis is also associated with hyperkalemia. (Harris 2018). Apart from these conditions, DKA (diabetic ketoacidosis) and digoxin toxicity can lead to hyperkalemia. Digoxin toxicity causes hyperkalemia by blocking the Na/K transporter leading to potassium to build up extracellularly and not be able to enter intracellularly (Regina 2025). In DKA, though the serum potassium is elevated there is a depletion of the total potassium.

Excretion

Excretion, per Dr. Topf, is the biggest player. An impairment of excretion of potassium will lead to hyperkalemia. Chronic kidney disease is a classic case of hyperkalemia and is related to chronic hyperkalemia. In the early stages of acute kidney injury and chronic kidney disease , the kidney adjusts its milieu to prevent hyperkalemia but at the later stages of CKD, hyperkalemia is seen.

A thorough medication review should be done as many medications can lead to hyperkalemia.

ACEi, ARBS, direct renin inhibitors, MRAs, aldosterone synthase inhibitors are classes of medications that affect the renin angiotensin aldosterone system. NSAIDS can lead to hyperkalemia through inhibition of prostaglandin synthesis, thereby reducing renin and aldosterone production (Aljadhey 2011). Antibiotics like trimethoprim sulfamethoxazole reduce the potassium excretion by way of competitive inhibition of epithelial sodium channel (similar to the potassium sparing diuretics, amilioride), thereby leading to hyperkalemia (Perazella 2000).  Tacrolimus, a calcineurin inhibitor, can lead to hyperkalemia by inactivating WNK. This stimulates the Na Cl co-transporter and decreases distal delivery of sodium (it shuts the K-switch off) which inhibits the principal cell from excreting sodium. WNK inactivation also decreases the activity of the ROM-K channels of the principal cells (Hoorn 2011).

Urinary obstruction is another etiology of hyperkalemia whereby the level of hyperkalemia is out of proportion to their level of AKI. The obstruction damages the eNaC preventing sodium reabsorption in the Principal Cell preventing K excretion. (Batlle 1981)

How to manage hyperkalemia?

Per Dr. Topf, fiber is important to be added/amped up because constipation contributes to hyperkalemia through decreased colonic excretion of potassium. Diuretics are also a good way to promote potassium excretion. Having a diet with potassium citrate, fruits, and vegetables is important, and the American diet in general has less potassium. At times, there might not be a clear etiology of hyperkalemia and one can think about ruling out hypoaldosteronism and can obtain a cosyntropin test (Tan 1981).

What about goal-directed medical therapy and hyperkalemia?

Goal-directed medical therapy (GDMT)* has been shown to reduce heart failure exacerbation, CKD progression, amongst other benefits but comes at the cost of hyperkalemia. Dr. Topf recommends continuing GDMT for as long as possible and can manage the hyperkalemia with diuretics. In addition to loop diuretics, even chlorthalidone can be used when the eGFR falls in the teens. Another option is a potassium binder to bind and facilitate excretion, such as sodium zirconium cyclosilicate or patiromer. There are still studies ongoing for these, however these medications are still costly. (Palmer 2019). Dr. Topf recommends that patients on ACEi can start SGLT2i prior to maximizing the ACEi dose.  In addition, Dr. Topf mentions that MRAs have not been shown to efficacious as part of GDMT for patients on dialysis (Tong 2025)

*Treatment of hyperkalemia in goal directed medical therapy in heart failure