Hyperkalemia

Drug-stacking hyperkalemia is usually a failure of renal potassium excretion, not an excessive potassium intake alone. In the collecting duct, aldosterone stimulates principal cells to reabsorb sodium through epithelial sodium channels (ENaC) and secrete potassium into the tubular lumen. Several medication classes interfere with this same pathway. ACE inhibitors, angiotensin receptor blockers (ARBs), and direct renin inhibitors reduce renin-angiotensin-aldosterone system activity and therefore reduce aldosterone-driven potassium secretion. Mineralocorticoid receptor antagonists such as spironolactone and eplerenone block aldosterone at its receptor. Amiloride and triamterene reduce potassium secretion by blocking ENaC directly. Each additional drug narrows the kidney’s remaining ability to excrete potassium; the risk is therefore convergent rather than simply additive. Trimethoprim, including the trimethoprim component of trimethoprim-sulfamethoxazole, also blocks ENaC in an amiloride-like manner. It behaves pharmacologically like an added potassium-sparing diuretic, not like a potassium-neutral antibiotic. NSAIDs can reduce renin release and renal blood flow. Heparin and low-molecular-weight heparins can suppress adrenal aldosterone synthesis. Cyclosporine and tacrolimus also impair renal potassium handling. Potassium supplements and potassium-containing salt substitutes add potassium to the load that the kidney must clear. CKD,...