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 ( EN aC) which explains the common observation of suppressed renin –angiotensin system and poor therapeutic response to ACE inhibitors. Blockade of EN aC 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 (200/140 mmHg), progressive edema (of at least 10 L), and overt proteinuria (18.5 g/24 h), despite combined administration of five antihypertensive drugs. Addition of amiloride (5 mg/day) to treatment resulted in resolution of edema, weight loss of 7 kg, reduction in blood pressure (150/100–125/81 mmHg), increased 24 h urinary sodium excretion (127–165 mmol/day), decreased eGFR (41–29 mL/min), and increased plasma potassium concentration (4.6–7.8 mmol/L). Blocking of EN aC 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 ACE i and spironolactone. The findings support that EN aC is active in NS and is a relevant target in adult NS patients.