Combination of Diuretics in States of Resistant Nephrotic Edema: a Case Presentation

While there remains no universally accepted definition for resistant edema, it is generally acknowledged as edema that fails to respond to maximally administered doses of diuretics. Nephrotic edema is characterized by high levels of proteinuria, notably urinary concentrations of serine proteases, which possess the ability to activate the epithelial sodium channel (ENaC), resulting in persistent fluid retention. Loop diuretics are typically preferred as first-line therapy for hypervolemia. However, the sustained activation of ENaC channels may lead to resistance to treatment. Consequently, the blockade of ENaC represents a potential therapeutic approach. We report the case of a 36-year-old man presenting with nephrotic edema managed with a combination of furosemide and human albumin. Despite an initially favorable response, the patient subsequently developed oliguria and progressive weight gain. On the third day, a regimen comprising amiloride (5 mg/day) and hydrochlorothiazide (50 mg/day) was initiated, resulting in complete resolution of edema after 11 days. No hyperkalemia was observed, with only a slight elevation in serum creatinine levels. Although clinical trials are limited, mounting evidence from human and animal studies supports the concept of nephrotic syndrome as an overfill phenomenon and underscores the potential benefits of ENaC blockers in the management of nephrotic edema.