What are other causes of hyperkalemia in a patient beyond chemotherapy-induced tumor lysis syndrome?

Other Causes of Hyperkalemia Beyond Tumor Lysis Syndrome

Hyperkalemia develops through three primary mechanisms: decreased renal potassium excretion, increased potassium intake, and transcellular potassium shifts from intracellular to extracellular space. 1

Mechanisms and Causes of Hyperkalemia

Decreased Renal Potassium Excretion

Medications are the most common iatrogenic cause of hyperkalemia, particularly in patients with underlying renal impairment, diabetes, heart failure, or advanced age. 1

RAAS Inhibitors and Related Drugs

• ACE inhibitors, angiotensin receptor blockers (ARBs), and mineralocorticoid receptor antagonists (MRAs) interfere with aldosterone production/secretion, impairing renal potassium excretion 1
• Direct renin inhibitors (aliskiren) and sacubitril/valsartan similarly affect the RAAS pathway 1
• These medications are particularly problematic when combined with renal dysfunction, as the incidence of hyperkalemia increases dramatically with severity of renal impairment 1

Potassium-Sparing Diuretics

• Spironolactone, triamterene, and amiloride block the kaliuretic effects of aldosterone at the collecting duct 1
• Risk is substantially elevated when combined with RAAS inhibitors 1

Antimicrobial Agents

• Trimethoprim-sulfamethoxazole blocks epithelial sodium channels in the collecting duct, reducing potassium secretion 1, 2
• High-dose trimethoprim (as used in Pneumocystis pneumonia) induces progressive, reversible increases in serum potassium 2
• Pentamidine similarly impairs renal potassium excretion 1
• Penicillin G at high doses can cause hyperkalemia 1

Immunosuppressants and Other Medications

• Cyclosporine and tacrolimus (calcineurin inhibitors) impair aldosterone secretion and tubular potassium handling 1
• Heparin suppresses aldosterone production 1
• NSAIDs reduce renin and aldosterone secretion while impairing renal function 1
• Beta-blockers cause transcellular potassium shifts and may reduce renal excretion 1

Renal Insufficiency

Chronic kidney disease is present in up to 73% of patients with hyperkalemia, and the incidence increases proportionally with severity of renal impairment. 1

• Hyperkalemia occurs in up to 40% of patients with chronic heart failure, often compounded by concurrent RAAS inhibitor use 1
• Acute kidney injury from any cause (including uric acid nephropathy, calcium phosphate precipitation, or drug-induced nephrotoxicity) impairs potassium excretion 1

Increased Potassium Intake/Administration

Excessive potassium intake rarely causes hyperkalemia in patients with normal renal function but becomes problematic with impaired excretion. 1

Dietary and Supplemental Sources

• Potassium supplements (prescribed or over-the-counter) 1
• Salt substitutes (e.g., DASH diet products containing potassium chloride) 1
• High-potassium foods: bananas, melons, orange juice 1
• Stored blood products contain significant potassium from hemolysis during storage 1

Herbal and Alternative Products

• Alfalfa, dandelion, hawthorne berry, horsetail, lily of the valley, milkweed, nettle, noni juice, Siberian ginseng, and dried toad skin 1
• Amino acids: aminocaproic acid, arginine, lysine 1

Transcellular Potassium Shifts

Potassium redistribution from intracellular to extracellular compartments can cause acute hyperkalemia without total body potassium excess. 3

• Beta-blockers impair cellular potassium uptake 1, 3
• Digitalis overdose inhibits Na-K-ATPase, causing potassium efflux from cells 1, 3
• Hypertonic mannitol creates osmotic gradients favoring potassium exit from cells 1, 3
• Succinylcholine causes massive potassium release from muscle cells 3
• Metabolic acidosis promotes hydrogen-potassium exchange across cell membranes 3

Endocrine and Metabolic Disorders

• Hypoaldosteronism (primary or secondary) reduces renal potassium excretion 3
• Addison's disease (adrenal insufficiency) causes combined aldosterone and cortisol deficiency 3
• Type IV renal tubular acidosis with hyporeninemic hypoaldosteronism, common in diabetic nephropathy 3

Tissue Breakdown and Cell Lysis

Beyond chemotherapy-induced tumor lysis, any condition causing massive cell destruction releases intracellular potassium. 4

• Rhabdomyolysis from trauma, prolonged immobilization, or drug toxicity 3
• Hemolysis (intravascular or massive) 3
• Severe burns with extensive tissue necrosis 3
• Spontaneous tumor lysis syndrome can occur without chemotherapy in rapidly proliferating malignancies 5

Critical Clinical Considerations

Pseudo-hyperkalemia

Always exclude pseudo-hyperkalemia before initiating treatment, as it represents falsely elevated laboratory values without true hyperkalemia. 1

• Caused by potassium release from blood cells during or after sampling (hemolysis, prolonged tourniquet time, fist clenching, thrombocytosis, leukocytosis) 1
• Repeat measurement with proper technique or arterial sampling if suspected 1

Additive Risk Factors

Multiple causes of hyperkalemia frequently coexist in the same patient, creating additive or synergistic effects. 3, 6

• A patient with moderate renal insufficiency taking an ACE inhibitor and NSAID who develops acute illness with decreased oral intake represents multiple simultaneous risk factors 1, 3
• Elderly patients are at particularly high risk due to age-related decline in renal function, polypharmacy, and comorbidities 1, 2

High-Risk Patient Populations

Hyperkalemia occurs in 10-55% of hospitalized patients depending on severity thresholds and underlying conditions. 1

• Patients with cardiovascular disease (heart failure, hypertension, coronary artery disease) combined with renal impairment, diabetes, and advanced age 1
• Patients receiving multiple medications affecting potassium homeostasis 1, 6
• Malnourished patients, chronic alcoholics, and those with folate deficiency have increased susceptibility to drug-induced hyperkalemia 2