high blood pressure, low blood potassium, and metabolic alkalosis in conjunction with a low plasma renin activity and a low aldosterone. Some people with the Liddle phenotype have Liddle syndrome, which involves a genetic mutation resulting in upregulation of the epithelial sodium channel (ENaC), located in the apical membrane of polarized epithelial cells in the late distal tubule and collecting duct of the kidney. Because Liddle phenotype usually involves an upregulation of ENaC channels, leading to retention of sodium and water and to hypokalemia, amiloride is useful as an ENaC channel inhibitor due to its promotion of sodium excretion and its potassium-sparing effects, restoring potassium to normal levels. Amiloride can be used as a monotherapy (single-drug therapy) or an adjunctive therapy alongside other diuretics (e.g. hydrochlorothiazide, furosemide) for the treatment of ascites and edema (swelling) due to cirrhosis of the liver. The 2012 clinical practice guidelines by the American Association for the Study of Liver Diseases (AASLD) states that amiloride can be used to treat ascites in place of spironolactone if it isn't tolerated (e.g. due to the side effect of gynecomastia), though amiloride isn't a preferred drug due to cost and lack of efficacy. Specific populations Diabetics People with diabetes are at higher risk for kidney problems, which increases their risk for hyperkalemia (high blood potassium). The use of amiloride in people with diabetes requires careful potassium and kidney function monitoring to prevent toxicity. Amiloride must be discontinued for at least 3 days prior to glucose tolerance testing, due to the risk for fatal hyperkalemia. Poor kidney function People with poor kidney function (e.g. blood urea nitrogen >30 mg/dL, or serum creatinine >1.5 mg/dL) are at high risk for hyperkalemia. Lactation There is no data on the use of amiloride in women that are breastfeeding. While diuretics can make lactation difficult, it is unlikely that amiloride would induce this effect in the absence of other diuretics. Pregnancy Data from the use of amiloride in animals suggests that it does not pose a risk to the developing fetus. However, when used in combination with the drug acetazolamide during the process of organ formation, amiloride increases the risk for kidney and ureter abnormalities. Limited human data from use during pregnancy suggests an association with a specific congenital penis abnormality if taken during the first trimester, as well as a risk for mild intrauterine growth restriction if taken throughout pregnancy. Contraindications Amiloride