Diuretic resistance is defined as a failure to achieve the therapeutically desired reduction in
edema despite a full dose of
diuretic. The causes of
diuretic resistance include poor adherence to
drug therapy or
dietary sodium restriction, pharmacokinetic issues, and compensatory increases in
sodium reabsorption in nephron sites that are not blocked by the
diuretic. To illustrate the pathophysiology and management of
diuretic resistance, we describe a patient with
nephrotic syndrome. This patient presented with generalized pitting
edema and
weight gain despite the use of oral
loop diuretics.
Nephrotic syndrome may cause mucosal
edema of the intestine, limiting the absorption of
diuretics. In addition, the patient's kidney function had deteriorated, impairing the tubular secretion of
diuretics. He was admitted for intravenous
loop diuretic treatment. However, this was ineffective, likely due to compensatory
sodium reabsorption by other tubular segments. The combination of
loop diuretics with
triamterene, a blocker of the
epithelial sodium channel, effectively reduced
body weight and
edema. Recent data suggest that
plasmin in nephrotic urine can activate the
epithelial sodium channel, potentially contributing to the
diuretic resistance in this patient. This case is used to illustrate and review the mechanisms of, and possible interventions for,
diuretic resistance.