Classic and Novel Mechanisms of Diuretic Resistance in Cardiorenal Syndrome

Despite the incompletely understood multiple etiologies and underlying mechanisms, cardiorenal syndrome is characterized by decreased glomerular filtration and sodium avidity. The underlying level of renal sodium avidity is of primary importance in driving a congested heart failure phenotype and ultimately determining the response to diuretic therapy. Historically, mechanisms of kidney sodium avidity and resultant diuretic resistance were primarily extrapolated to cardiorenal syndrome from non-heart failure populations, yet the mechanisms appear to differ between these populations. Recent literature in acute decompensated heart failure has refuted several classically accepted diuretic resistance mechanisms and reshaped how we conceptualize diuretic resistance mechanisms in cardiorenal syndrome. Herein, we propose an anatomically based categorization of diuretic resistance mechanisms, to establish the relative importance of specific transporters and translate findings toward therapeutic strategies. Within this categorical structure, we discuss classical and novel mechanisms of diuretic resistance.