A 66-year-old man comes to the office for routine follow-up. He has had mild fatigue but otherwise feels well. The patient has a history of hypertension, type 2 diabetes mellitus, hyperlipidemia, chronic kidney disease, and ischemic cardiomyopathy. Temperature is 36.7 C (98.1 F), blood pressure is 122/70 mm Hg, and pulse is 82/min. Physical examination shows moist mucous membranes. A 2/6 holosystolic murmur at the apex is unchanged from the previous examination. The patient has trace edema in the bilateral lower extremities. Laboratory results are as follows:
| Sodium | 135 mEq/L |
| Potassium | 6.0 mEq/L |
| Bicarbonate | 24 mEq/L |
| Blood urea nitrogen | 38 mg/dL |
| Creatinine | 2.4 mg/dL |
| Calcium | 8.2 mg/dL |
| Glucose | 196 mg/dL |
Two months ago, creatinine was 2.3 mg/dL. ECG shows normal sinus rhythm with no other abnormalities. Which of the following is the best next step in management of this patient?
Common medications that cause hyperkalemia | |
Medication | Mechanism |
ACE inhibitor, ARB | Decreases aldosterone secretion (inhibition of AT II/AT II receptor) + inhibits ENaC |
Cyclosporine | Blocks aldosterone activity |
Digitalis | Inhibits Na+/K+-ATPase |
Heparin | Blocks aldosterone production |
Nonselective | Interferes with β2-mediated intracellular potassium uptake |
NSAID | Decreases renal perfusion → decreased potassium delivery to the collecting ducts |
Potassium-sparing diuretic | Inhibits ENaC or aldosterone receptor |
Succinylcholine | Causes extracellular leakage of potassium through acetylcholine receptors |
Trimethoprim | Inhibits ENaC |
ARB = angiotensin II receptor blocker; AT = angiotensin; ENaC = epithelial sodium channel; Na+/K+-ATPase = sodium-potassium pump; NSAID = nonsteroidal anti-inflammatory drug. | |
In the outpatient setting, hyperkalemia is most often caused by reduced urinary potassium excretion due to renal insufficiency or medications/disorders that impair the renin-angiotensin axis. Less common causes include the movement of potassium from the intracellular to the extracellular space (eg, uncontrolled hyperglycemia, metabolic acidosis) or increased tissue catabolism (eg, trauma, tumor lysis syndrome).
Hyperkalemia is usually asymptomatic until potassium rises to ≥6.5 mEq/L, but acute hyperkalemia can sometimes cause symptoms at lower levels. Common manifestations include ascending muscle weakness with flaccid paralysis, cardiac arrhythmia (eg, heart block, bradycardia), and ECG changes (eg, peaked T waves → short QT interval → QRS widening → sine wave).
Urgent therapy (eg, calcium gluconate, insulin with glucose) is typically reserved for ECG changes, potassium ≥6.5 mEq/L, and/or rapidly rising potassium due to tissue breakdown, none of which are present in this patient (Choice A). The next step is to exclude acute secondary causes (eg, uncontrolled hyperglycemia, tumor lysis syndrome). A review of recent/current medications should be conducted to determine whether any trigger hyperkalemia. Common offending agents include nonselective beta-adrenergic blockers, potassium-sparing diuretics (eg, triamterene), ACE inhibitors, angiotensin II receptor blockers, and nonsteroidal anti-inflammatory drugs. This patient with chronic kidney disease and a significant cardiac history is likely on a renin-angiotensin system inhibitor, which often triggers hyperkalemia.
(Choice B) Patients with persistent, unexplained hyperkalemia should be evaluated further for hypoaldosteronism with serum renin and aldosterone levels. However, this patient's medications should first be reviewed.
(Choice C) Uncontrolled hyperglycemia due to insulin deficiency can shift potassium out of cells, leading to hyperkalemia. However, these patients tend to have significant hyperglycemia (>300 mg/dL) and, often, anion gap metabolic acidosis due to ketoacidosis. This patient's normal bicarbonate and lack of significant hyperglycemia make this less likely.
(Choice D) Urinalysis has limited value for evaluating hyperkalemia. However, urine electrolytes can help differentiate renal from extrarenal causes of hyperkalemia; this might be indicated if no offending medications are found.
Educational objective:
The most common causes of hyperkalemia include renal insufficiency, medications, and disorders impairing the renin-angiotensin axis. Common offending medications include nonselective beta-adrenergic blockers, potassium-sparing diuretics (eg, triamterene), ACE inhibitors, angiotensin II receptor blockers, and nonsteroidal anti-inflammatory drugs.