Abstract Worsening congestion is the main reason for hospitalization of most acute heart failure (AHF) patients. However, most patients are discharged with residual congestion, resulting in early readmissions that portend poor outcomes. Diuretics remain the mainstay of therapy. Nevertheless, these drugs stimulate the renin-angiotensin–aldosterone (RAA) axis and the sympathetic system and elicit adaptive responses in the nephron that may be counterproductive and lead to diuretic resistance. Renal failure and AHF are common and coexist in up to 40% of cases. […]