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

Abstract

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 (200/140 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 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.

Keywords: ENaC; plasmin; protease; proteinuria.

Figure 1

(A): Overview of the increasing doses and numbers of the antihypertensive and diuretic drugs in a timeline. (B) Blood pressure decreased slowly and insufficiently despite several antihypertensive drugs, but at administration of amiloride (week 15), blood pressure, and weight declined promptly and effectively. (C) Combined treatment directed at aldosterone/ENaC resulted in severe hyperkalemia and a decline in kidney function. (D) Addition of amiloride increased urinary sodium excretion. Furthermore, proteinuria decreased.