Exploring Kidney functions as a key barrier to effective diuresis in Congestion Refractory Heart Failure: Insights from the DEA-HF Clinical Trial

Introduction Kidney dysfunction hinders effective decongestion in chronic heart failure (HF). Key factors that affect diuretic efficacy are HF severity, glomerular filtration rate (GFR), acid-base balance, and diuretic type, dosage, and treatment duration. Managing patients with chronic HF and persistent volume overload despite guideline-directed medical therapy and optimized oral diuretics remains a significant clinical challenge. To address this, diuretic combinations are frequently employed. Purpose To compare and characterize the effect of estimated GFR (eGFR) and serum bicarbonate levels on three distinct diuretic regimens in congestion-refractory patient population. Method Sub-analysis of the prospective, randomized, cross-over DEA-HF trial. Forty-two patients received weekly one of three high-intensity diuretics, in a randomized order: IV furosemide 250mg; oral metolazone 5mg+IV furosemide 250mg; and IV acetazolamide 500mg+IV furosemide 250mg. Efficacy was evaluated by total sodium excretion and urine volume, as well as serum NT-ProBNP, congestion score, body weight, and lung ultrasound B-lines. Results All diuretic regimens demonstrated a consistent pattern, with natriuresis efficacy correlating with eGFR and serum bicarbonate. A single diuretic session (regimen-independent) resulted in significantly higher natriuresis in patients with higher eGFR: estimated mean Sodium exertion of 5593mg (95% CI:4929-6257) in patients with eGFR>45ml/min/1.73m2 compared to 4929mg (95% CI:3694-4891, P<0.01) in patients with eGFR 30-45ml/min/1.73m2 and 2934mg (95% CI:2345-3522, P<0.001) in patients with eGFR<30ml/min/1.73m2. P for interaction was not significant. Urine volume followed a similar trend. Nevertheless, patients in all eGFR groups achieved statistically comparable significant reductions in body weight, serum NT-ProBNP, congestion score, and lung ultrasound B-lines. Regardless of the diuretic regimen, higher baseline bicarbonate levels were associated with a greater diuretic effect. Worsening of renal function was more common with eGFR<30ml/min/1.73m² (12%) than in eGFR 30-45ml/min/1.73m² (7.7%) or >45ml/min/1.73m² (6.3%), without associated HF or renal-related admissions. Conclusions In patients with congestion-refractory chronic HF, natriuresis and diuresis efficacy were positively correlated with higher eGFR. No specific regimen showed a clear advantage in those with lower eGFR. Higher serum bicarbonate was associated with improved diuresis efficacy. The mechanism of improved diuresis with elevated serum bicarbonate remains to be determined. Although natriuresis effectiveness demonstrated a clear dependence on eGFR, all eGFR groups achieved decongestion with high dose diuretic therapy.