Effective fluid removal remains a major challenge in chronic heart failure patients with kidney dysfunction. The 2025 European Society of Cardiology (ESC) meeting emphasized the need to personalize diuretic therapy to renal function and metabolic parameters for better congestion control.

A sub-analysis of the prospective, randomized, cross-over DEA-HF trial evaluated 42 patients with persistent congestion despite guideline-directed therapy. Participants received three weekly high-intensity diuretic regimens in random order: intravenous furosemide 250 mg, oral metolazone 5 mg plus IV furosemide, and IV acetazolamide 500 mg plus IV furosemide.

Natriuresis and urine output are consistently correlated with estimated glomerular filtration rate (eGFR) and serum bicarbonate. Patients with eGFR > 45 mL/min/1.73 m² had significantly higher sodium excretion and urine volume than those with impaired renal function (p < 0.01). Nonetheless, all groups achieved meaningful reductions in body weight, NT-proBNP, congestion scores, and lung ultrasound B-lines.

While worsening renal function occurred more frequently in patients with eGFR < 30 mL/min/1.73 m², no hospitalizations ensued. Elevated baseline bicarbonate levels also enhanced diuretic effectiveness, suggesting a potential metabolic mechanism that warrants further exploration in future trials.