High Potassium (Hyperkalemia): Causes and When It Is an Emergency

About 98% of the body's potassium is inside cells, and only a small part circulates in the blood. A seemingly small change in blood concentration can therefore mean a large change in the gradient across the cell membrane, on which the resting potential of cells depends. Two mechanisms maintain balance. The first is the rapid shifting of potassium into or out of cells, in which insulin, catecholamines (beta-2 receptors), blood pH and the sodium-potassium pump take part. The second, slower but decisive for the daily balance, is renal excretion: in the distal nephron aldosterone increases the secretion of potassium into urine in exchange for sodium reabsorption.

This yields a division of the causes of hyperkalemia into three categories. The first is excessive intake, which alone is rarely enough if the kidneys work normally, because a healthy kidney can excrete many times more potassium than a typical diet contains. The second is a shift of potassium from cells into the blood (acidosis, insulin deficiency with hyperglycemia, tissue breakdown such as rhabdomyolysis, burns, tumor lysis, non-selective beta-blockers). The third, by far the most common, is reduced renal excretion, caused by kidney failure, a lack of aldosterone or of its action, or by drugs. A 2013 review notes that when the cause of hyperkalemia is assessed, the problem usually turns out to be renal potassium excretion rather than excess intake or transcellular shift.

Before potassium is treated as truly elevated, a doctor should make sure the blood sample has not been distorted. Blood cells contain far more potassium than plasma, so any damage to the cells or improper storage of the sample can 'wash out' potassium into the serum and artificially raise the result. This is pseudohyperkalemia, also called spurious hyperkalemia, and the phenomenon is well known in laboratory diagnostics.

The most common sources of pseudohyperkalemia include a difficult blood draw (a tourniquet left on too long, multiple punctures, a thin needle, vigorous fist clenching), rough transport of the sample, for instance through a pneumatic tube system, and centrifugation that is too late or storage of the sample in a refrigerator, which disturbs the sodium-potassium pump so that potassium leaks out of the blood cells. A separate group is made up of diseases in which the number of cells in the blood is very high. In an observational study of 283 controls and 161 patients with reactive thrombocytosis, the frequency of hyperkalemia was 34% with a platelet count above 500 thousand/µl, versus 9% with a count below 250 thousand/µl, and serum potassium exceeded plasma potassium by more the more platelets there were. The authors judged the increment to be an artifact: platelets release potassium as the sample clots in the tube.

Practical conclusion: with raised potassium in a person without symptoms and without clear risk factors, the first step should be a properly collected follow-up test. At the same time, you must not automatically assume the result is an error just because 'the patient looks well'; in people with kidney disease or those taking risky drugs the repeat should happen quickly and in a way that ensures a reliable sample.

If hyperkalemia is real, the first suspect is usually a drug. The greatest importance attaches to drugs acting on the renin-angiotensin-aldosterone system (ACE inhibitors, ARBs, mineralocorticoid receptor antagonists such as spironolactone, eplerenone and finerenone), potassium-sparing diuretics (amiloride, triamterene), trimethoprim (including in co-trimoxazole), non-steroidal anti-inflammatory drugs, heparin, calcineurin inhibitors (cyclosporine, tacrolimus), potassium supplements and, in poisoning, digoxin. The risk rises when several such drugs are used together or when the kidneys work less well, for example in diabetes, heart failure and chronic kidney disease.

The European expert consensus on hyperkalemia in patients with cardiovascular disease treated with RAA system inhibitors draws attention to an important paradox. These drugs are the basis of therapy for heart failure, hypertension, diabetes with kidney damage and chronic kidney disease, because they have been shown to reduce mortality and complications. At the same time, about half of patients with chronic kidney disease and heart failure experience two or more recurrences of hyperkalemia a year, and a significant proportion of patients have their dose reduced or the drug stopped after just one raised result.

That is why, although high potassium is a real danger, stopping a drug on your own is not a good solution. The decision to reduce the dose, change the drug, add a drug that binds potassium in the gut (for example patiromer or sodium zirconium cyclosilicate), intensify a loop diuretic or change the diet is made by a doctor after weighing risks and benefits in the individual patient. Observational data do not prove causally that discontinuation does harm, but they consistently show that 'zero tolerance' for any rise in potassium is not a good strategy.

In a person with healthy kidneys, a diet rich in potassium, that is vegetables, fruit, legumes and nuts, practically never causes hyperkalemia, because the kidneys increase excretion of the excess. The risk starts to rise only when glomerular filtration is reduced or when potassium-sparing drugs are taken at the same time. In such situations, products that are easy to overlook may also matter: table-salt substitutes based on potassium chloride, potassium supplements, some drinks and electrolyte powders, and herbal concentrates and juices with a high potassium content.

The KDIGO Controversies Conference on potassium in kidney disease noted that a growing body of data points to a favorable association of a plant-based diet with health outcomes, while good studies showing whether limiting dietary potassium actually restores normal blood potassium are lacking. A change in paradigm was suggested: from a simple ban on potassium-rich foods toward eating patterns associated with better outcomes. In practice this means that in patients with chronic kidney disease dietary decisions should be individual and made with a nephrologist or clinical dietitian, not on the basis of general lists of 'forbidden' vegetables.

Moderately raised potassium usually gives no symptoms, which is why it is so often found by chance. When symptoms do appear, they are nonspecific: muscle weakness, tingling, palpitations, nausea. In severe hyperkalemia, muscle paralysis, bradycardia, conduction disturbances and ventricular fibrillation can occur. Typical ECG changes include tall, narrow, peaked T waves, a prolonged PR interval, a widened QRS complex and, in the most severe cases, the so-called sine-wave pattern.

Two conclusions follow from this study that may seem contradictory but are not. First, a normal ECG does not exclude dangerous hyperkalemia, so high potassium must not be dismissed just because 'the ECG is fine'. Second, the final decision about the intensity of treatment rests on the potassium value, the speed of its rise, symptoms, coexisting diseases and kidney function, not on the ECG alone. That is why doctors usually order a repeat measurement, an ECG and kidney tests together.

Different guidelines use slightly different thresholds for grading the severity of hyperkalemia (commonly seen divisions are 5.5–5.9 mmol/l as mild, 6.0–6.4 as moderate and 6.5 or more as severe), so treat these numbers as indicative and leave decisions to the doctor. In hospital, treatment of severe or symptomatic hyperkalemia includes intravenous calcium salts, which stabilize the cardiac muscle cell membrane, insulin with glucose and inhaled beta-2 agonists, which shift potassium into cells, followed by removal of the excess potassium from the body (diuretics, gut potassium binders, dialysis) and elimination of the cause.

A review published in Mayo Clinic Proceedings in 2021 notes that there is no single, universally accepted consensus on thresholds and frequency of potassium checks, and that monitoring should be individualized, with more frequent tests in people with chronic kidney disease, diabetes, heart failure, a history of hyperkalemia and those taking RAA system inhibitors. That is an honest message for the patient: there is no one number that means the same thing for everybody, so it matters that checks are matched to your own risk.

Equally misleading is the belief that 'water will flush out potassium'. The kidneys excrete potassium depending on the delivery of sodium and water to the distal nephron and on aldosterone activity; increasing the amount of fluid drunk does not solve the problem in a person with diseased kidneys, and in heart or kidney failure may even do harm. In hospital, on the other hand, loop diuretics are used under medical supervision when the patient has preserved urine output.

High potassium is the kind of result in which two extreme approaches are worst: panic after a single overestimated measurement, and disregard of a value that really threatens the heart rhythm. The sensible middle path is a series of simple questions: was the sample good, how do the kidneys work, what am I taking, and how do I feel. For most people without symptoms the answer will be a repeat test. For people with kidney disease, diabetes or heart failure on RAA system inhibitors, it is more important to know that hyperkalemia is not a verdict against treatment, but a signal for the doctor to adjust therapy.

A practical tip for anyone taking drugs that affect potassium: ask for potassium and creatinine to be checked after starting treatment, after a dose increase, and during acute illness with vomiting, diarrhea or dehydration, when kidney function may temporarily worsen. It is one of the cheaper and more effective forms of prevention in cardiology and nephrology.