Potassium Sparing Diuretics

Potassium-sparing diuretics reduce sodium reabsorption in the late distal tubule and collecting duct without increasing potassium loss. They give weak diuresis alone and are mainly used to prevent hypokalaemia with thiazides or loop diuretics, and for specific indications such as lithium-induced diabetes insipidus.

Members. Amiloride and triamterene (epithelial sodium channel blockers). The mineralocorticoid receptor antagonists spironolactone and eplerenone also spare potassium but act through a receptor mechanism.

Mechanism. Blockade of the luminal epithelial sodium channel in principal cells reduces sodium entry, so the lumen is less negative and potassium and hydrogen ion secretion fall. Only 1% to 3% of filtered sodium is affected, so diuresis is modest.

Additional actions. Amiloride blocks lithium entry through the channel, reducing nephrogenic diabetes insipidus. Both drugs treat Liddle syndrome, which is caused by overactive epithelial sodium channels.

Pharmacokinetics. Amiloride is excreted unchanged by the kidney, with a half-life of 6 to 9 hours. Triamterene is metabolised in the liver to an active sulphate conjugate and has a half-life of about 2 to 3 hours.

• Amiloride: oral; used alone or with thiazide or loop diuretics.
• Triamterene: oral; fixed combination with hydrochlorothiazide.
• Spironolactone and eplerenone: receptor antagonists with additional cardiac and renal benefit.

• Prevention of hypokalaemia: amiloride 5 to 10 mg daily with a loop or thiazide diuretic, or triamterene 50 to 100 mg daily.
• Oedema and hypertension: amiloride 5 to 10 mg daily (maximum 20 mg); triamterene 150 to 250 mg daily in divided doses.
• Lithium-induced nephrogenic diabetes insipidus: amiloride 5 to 10 mg daily.
• Liddle syndrome: amiloride or triamterene with salt restriction.
• Resistant hypertension and primary aldosteronism: amiloride 10 to 20 mg daily if spironolactone is not tolerated.
• Selection: prefer an MRA in heart failure and cirrhosis, and a potassium-sparing agent when gynaecomastia or hormonal effects are a problem.

Contraindications. Hyperkalaemia (potassium over 5.5 mmol/L), acute kidney injury, anuria, severe renal impairment, Addison disease, and use with potassium supplements or other potassium-sparing agents. Amiloride is contraindicated in diabetic nephropathy.

Adverse effects. Hyperkalaemia, hyponatraemia, gastrointestinal upset, headache, rash and metabolic acidosis. Triamterene: kidney stones, megaloblastic anaemia through folate antagonism, photosensitivity, blue fluorescence in urine, and acute kidney injury with NSAIDs.

Hyperkalaemia treatment. Obtain an electrocardiogram. For electrocardiogram changes give calcium gluconate 10% 10 to 30 mL intravenously, then insulin 10 units with 25 g glucose, and nebulised salbutamol 10 to 20 mg. Stop the potassium-raising drugs.

Interactions. ACE inhibitors, angiotensin receptor blockers, spironolactone, eplerenone, potassium supplements and salt substitutes, trimethoprim, ciclosporin, tacrolimus and heparin raise potassium. NSAIDs risk acute kidney injury. Amiloride raises digoxin levels. Lithium clearance falls.

Monitoring. Potassium and creatinine at 1 week, 1 month, then every 3 to 6 months. Stop when potassium exceeds 5.5 mmol/L.

Sick day rule. Withhold during dehydrating illness.

Special groups. Older adults and patients with diabetes or chronic kidney disease have the highest risk of hyperkalaemia. Pregnancy: avoid. Breastfeeding: avoid because of limited data. Renal impairment: avoid when eGFR is under 30 mL/min/1.73 m2.