Amiloride resolves resistant edema and hypertension in a patient with nephrotic syndrome; a case report

Sodium and fluid retention is a hallmark and a therapeutic challenge of the nephrotic syndrome (NS). Studies support the overfill theory of NS with pathophysiological proteolytic activation of the epithelial sodium channel (ENaC) which explains the common observation of suppressed renin -angiotensin system and poor therapeutic response to ACE inhibitors. Blockade of ENaC by the diuretic amiloride would be a rational intervention compared to the traditionally used loop diuretics. We describe a 38-year-old male patient with type1 diabetes who developed severe hypertension (200/140mmHg), progressive edema (of at least 10L), and overt proteinuria (18.5g/24h), despite combined administration of five antihypertensive drugs. Addition of amiloride (5mg/day) to treatment resulted in resolution of edema, weight loss of 7kg, reduction in blood pressure (150/100-125/81mmHg), increased 24h urinary sodium excretion (127-165mmol/day), decreased eGFR (41-29mL/min), and increased plasma potassium concentration (4.6-7.8mmol/L). Blocking of ENaC mobilizes nephrotic edema and lowers blood pressure in NS. However, acute kidney injury and dangerous hyperkalemia is a potential risk if amiloride is added to multiple other antihypertensive medications as ACEi and spironolactone. The findings support that ENaC is active in NS and is a relevant target in adult NS patients.