Expansion of extracellular fluid volume is central to the
pathophysiology of heart failure. Increased extracellular fluid leads to
elevated intracardiac filling pressures, resulting in a constellation
of signs and symptoms of heart failure referred to as congestion. Loop
diuretics are one of the cornerstones of treatments for heart failure,
but in contrast to other therapies, robust clinical trial evidence to
guide the use of diuretics is sparse. A nuanced understanding of renal
physiology and diuretic pharmacokinetics is essential for skillful use
of diuretics in the management of heart failure in both the inpatient
and outpatient settings. Diuretic resistance, defined as an inadequate
quantity of natriuresis despite an adequate diuretic regimen, is a major
clinical challenge that generally portends a poor prognosis. In this
review, the authors discuss the fundamental mechanisms and physiological
principles that underlie the use of diuretic therapy and the available
data on the optimal use of diuretics.