Renal Mechanisms of Diuretic Resistance in Congestive Heart Failure

This study reviews the renal aspects of diuretic resistance occurring in diuretic treatment, mostly with loop diuretics of congestive heart failure. A short discussion on the different classes of diuretics, including the recently introduced sodium-glucose transporter 2 inhibitors, and their mechanism of action in the nephron is provided, followed by a summary of recent data discussing the different causes and pathophysiological mechanisms of diuretic resistance. The major cause of diuretic resistance appears to be localized within the distal tubule. Traditionally, the concept of compensatory post-diuretic sodium reabsorption (CPDSR) was considered the major cause of diuretic resistance; however, recent studies have disputed this traditional concept and demonstrated that patients with congestive heart failure are in constant sodium-avid state. Finally, the different options of therapeutic strategies, combining different classes of diuretics are summarized.