*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.
All that follows is from the above resource.
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.
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.
CME Partner: VCU Health CE
The Curbsiders are partnering with VCU Health Continuing Education to offer continuing education credits for physicians and other healthcare professionals. Visit curbsiders.vcuhealth.org and search for this episode to claim credit.
Hyperkalemia and Hypokalemia Pearls
In a case of hyperkalemia, the first step is to rule out any cause of pseudohyperkalemia: such as hemolyzed samples
Hyperglycemia can cause hyperkalemia due to solute drag; if the sugars can be controlled, then that will aid in the control of hyperkalemia.
Medications can also lead to hyperkalemia so it’s important to do a thorough medication check.
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
Even in dialysis patients who have hyperkalemia, there are roles for potassium binders
Proton pump inhibitors often cause hypomagnesemia and related hypokalemia; with repletion of magnesium, the potassium should improve.
Rhabdomyolysis is diagnosed primarily through a blood test that measures high levels of creatine kinase (CK), a protein released into the blood when muscle tissue is damaged. [1]
Doctors combine this blood test with a review of your medical history, recent physical activity, and physical examination. [1, 2]
Common Symptoms
Doctors look for signs of severe muscle injury. The classic signs include: [1]
Muscle pain or severe aches (especially in the thighs, shoulders, calves, or lower back)
Muscle weakness or trouble moving your arms and legs
Note: Not everyone has all three symptoms. Some people only feel tired, stiff, or sore.
Key Diagnostic Tests
Creatine Kinase (CK) Blood Test: This is the most important test. A CK level that is five times higher than normal (or over 1,000 to 5,000 IU/L) strongly points to rhabdomyolysis. [1, 2]
Urine Test (Urinalysis): Doctors check your urine for myoglobin, a muscle protein that turns urine dark. A urine dipstick might show a false positive for blood, but a microscope will show no actual red blood cells. [1, 2]
Kidney Function Tests: Blood tests for creatinine and blood urea nitrogen (BUN) check if muscle breakdown products have started to harm your kidneys. [1, 2]
Electrolyte Tests: Blood tests check for dangerous shifts in potassium, calcium, and phosphorus. [1, 2]
ECG (Electrocardiogram): This heart test checks for irregular heart rhythms caused by high potassium levels. [1, 2]
“In the context of hyperkalemia, TLS stands for Tumor Lysis Syndrome, a life-threatening oncological emergency where rapid breakdown of cancer cells floods the bloodstream with intracellular contents, including large amounts of potassium.”
Overview of TLS
Definition: A group of metabolic disturbances that happens when a massive number of cancer cells die at once.
Timing: It usually occurs within 24 to 72 hours after starting chemotherapy, but it can also happen spontaneously in fast-growing cancers like leukemia or lymphoma. [1, 2, 3, 4, 5]
The Metabolic Tetrad
TLS is characterized by four major electrolyte and chemical imbalances: [1]
Hyperkalemia: High blood potassium (released from inside the destroyed cells), which can cause fatal heart rhythms.
Hyperphosphatemia: High blood phosphorus from cell destruction.
Hypocalcemia: Low blood calcium, which happens because the excess phosphorus binds to calcium.
Hyperuricemia: High uric acid from the breakdown of nucleic acids, which can lead to kidney injury. [1, 2, 3, 4, 5]
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)
Hyperkalemia and the Dialysis Patient
In patients on dialysis, studies have shown that potassium binders like sodium zirconium cyclosilicate can be used which has shown to decrease the potassium level (Fishbane 2025). Dr. Topf recommends adjusting the dialysate bath which creates a gradient to allow for the management of hyperkalemia.
When to Call Nephrology?
Dr. Topf recommends calling nephrology at any time when questions arise and also when there is a question of possibly needing higher doses of medications to get control of the potassium.
Hypokalemia
How To Approach/How to Build a Framework
Dr. Topf says that hypokalemia is to be feared just as hyperkalemia is. So be on the lookout! Dr. Topf mentions that there is a U shaped curve and the ideal spot is between 4-5.1. Interestingly, in patients with cardiovascular disease even low normal levels of potassium can increase the risk for ventricular arrhythmias (Jons 2025).
Dr. Topf’s framework for approaching hypokalemia is similar to hyperkalemia: intake, distribution, and excretion.
Intake
Per Dr. Topf, a lack of adequate intake alone doesn’t lead to hypokalemia. It can contribute to comorbidities causing hypokalemia such as alcohol abuse disorder, malnutrition, and eating disorders to name a few.
Distribution
Look into pathologies or medication use where potassium will get shifted intracellularly which include insulin, Beta agonists, and also periodic paralysis [link is to a Google search on periodic paralysis] as well.
Excretion
When it comes to excretion there can be extra-renal causes and renal causes of hypokalemia. Extra renal causes include fistulas, laxatives, and diarrhea; whereas, renal causes include diuretics, Barter, Gitelmans, metabolic alkalosis, primary hyperaldosteronism, licorice, hypomagnesemia, renal tubular acidosis (Kardalas 2018).
Dr. Topf says that in cases of hypokalemia, look at urine potassium by a spot urine potassium or a urine potassium to urine creatinine ratio. In hypokalemia, a spot urine potassium above 20 mEq/L is concerning for inappropriate renal loss (and a potential renal cause) whereas < 20 mEq/L suggests an extrarenal cause (Wang, 2025). Per Dr. Topf, using the urine potassium to urine creatinine ratio (in mEq K/mmol Cr), a ratio that is less than 2.5 suggests an extrarenal cause and a ratio more than 2.5 suggests a renal cause.
Proton-pump inhibitor (PPI) use is a common cause of hypokalemia, which is thought to be due to hypomagnesemia. PPIs impair the TRPM6/TRPM7 channel, reducing magnesium absorption in the gut (Gommers 2022). Magnesium deficiency will lead to an unblocking of the ROMK channel in the kidney thereby leading to an excessive potassium wasting. (Tran 2025). The way to manage this PPI induced hypokalemia is to stop the PPI completely. Dr Topf mentions that if the patient goes back on the PPI after not being on it for some time it will still potentiate the hypomagnesemia and hypokalemia.
