Contemporary Approaches to Kidney Dysfunction and Diuretic Resistance in Acute Decompensated Heart Failure

Kidney dysfunction, characterized by either reduced estimated glomerular filtration rate (eGFR) of <60 ml/min per 1.73 m2 or reduced urinary response to diuretic therapy, is among one of the most powerful risk factors for mortality and adverse cardiovascular events among patients with acute decompensated heart failure (ADHF). Classically postulated hemodynamic mechanisms-including low cardiac output, arterial underfilling and venous congestion-likely interact through complex multi-directional pathways to contribute to kidney dysfunction in ways that remain incompletely understood. However, trials of therapies designed to improve cardiovascular hemodynamics have not consistently translated into improvements in kidney function. Non-hemodynamic contributors such as neurohormonal activation, inflammation, and endothelial dysfunction likely also play important roles in the development of kidney dysfunction in ADHF. A major challenge of the management of ADHF is intense tubular sodium and water avidity, leading to congestion that can be resistant to diuretic therapy. Overcoming diuretic resistance frequently requires escalation of loop diuretics as well as combination diuretic strategies targeting multiple nephron segments, and monitoring of diuretic response to guide titrations of diuretic therapy. Recent studies have also evaluated the safety of initiation of guideline directed medical therapy (GDMT) during hospitalizations for ADHF. Even though GDMT use has been shown to reduce cardiovascular events, rates of use remain low and hospitalizations for ADHF represent opportunities for initiation and/or resumption of GDMT. Many of therapies in ADHF, including decongestion and GDMT initiation, are associated with acute declines in kidney function that remain difficult to interpret and may be misleading if used in isolation without the larger clinical context to guide treatment decisions. Lastly, emerging novel targets for decongestion are being evaluated with the ultimate goal of achieving decongestion without declines in kidney function.