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A 61-year-old man with a history of heart failure with reduced ejection fraction (HFrEF) from underlying coronary artery disease (CAD) presents with increasing symptoms of congestion and volume overload. He has a history of difficult-to-maintain volume status requiring high doses of diuretics as an outpatient. Despite increasing his baseline diuretic dosing at home, his symptoms progress and he is admitted for additional therapy. In the setting of high diuretic requirements, he is felt to have diuretic resistance. Instead of initiating therapy with extremely high doses of intravenous loop diuretics, ultrafiltration is initiated for volume management. The patient undergoes successful ultrafiltration over the next few days with return to his baseline volume status. He is subsequently discharged on a standard diuretic regimen with resolution of his symptoms.


Despite many advances in the therapy of heart failure (HF), hospitalization for worsening HF still accounts for a significant portion of total hospital admissions in the United States. Additionally, rehospitalization after an index HF hospitalization remains a significant challenge in the treatment of HF.1,2 The risk of rehospitalization is significantly higher when inadequate volume removal occurs during a hospital stay, with up to 50% of patients having little or no weight loss during inpatient treatment.3,4 Therefore, effective strategies to completely decongest patients are crucial to appropriate HF management.


Diuretic resistance occurs when a decrease in diuresis and natriuresis to medical therapy is observed, and is estimated to occur in 25% to 30% of patients with HF.5 Although variable definitions of diuretic resistance have been proposed, the common themes among criteria are inadequate augmentation of total urine output, urine sodium excretion, weight loss, or symptom relief to large doses of loop diuretics.6 Although incompletely understood, diuretic resistance may occur either from renal tubular hypertrophy following long-term exposure to loop diuretics or a decreased response to diuretics after the administration of an initial dose (Figure 33-1).7 The latter phenomenon is likely driven by neurohormonal activation (Figure 33-2), which can lead to a worsening feedback loop in the treatment of HF (Figure 33-3).8 The use of ultrafiltration allows volume removal without the use of diuretics, and therefore can bypass diuretic resistance and the feedback loop.

Figure 33-1

Mechanisms of diuretic resistance: acute furosemide exposure may cause a diminished response to subsequent doses without changes within the tubule, whereas chronic furosemide exposure leads to distal tubule hypertrophy. Abbreviations: TAL, thick ascending limb; DT, distal tubule.

Figure 33-2

Effects of elevated neurohormones within the nephron. Abbreviations: GFR, glomerular filtration rate; AT2, angiotensin II.

Figure 33-3

Negative feedback due to diuretic resistance.

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