Renal Diuretic Delivery is Highly Variable in Hospitalized Decompensated Heart Failure Patients and Associated with Diuretic Resistance

Introduction It is often assumed that diuretic delivery to the site of action is adequate if the route of administration is intravenous (IV). Although IV administration circumvents gastrointestinal bioavailability, the diuretic must be delivered and secreted into the tubular lumen induce diuresis. In ADHF, perturbations such as reduced renal perfusion and renal dysfunction may impact delivery to the tubular site of action. Hypothesis There will be substantial between-patient heterogeneity in renal diuretic delivery across hospitalized AHDF patients receiving IV diuretics. Methods ADHF patients receiving IV diuretics at Yale New Haven Hospital underwent intensively supervised timed urine collection. Renal diuretic delivery was defined as the percentage of loop diuretic recovered unchanged in the urine in the 6h after IV diuretic administration. Results 105 patients were studied after a median 80 mg (IQR 40-160mg) IV furosemide equivalents, with a median of 30 mg (12-59 mg) of unchanged loop diuretic recovered in the urine. Thus, 37% (21-54%) reached the site of action, substantially less than that reported in normal subjects (∼50-70%, p 0.1). A modest correlation between better renal filtration (eGFR r=0.23, p=0.02; creatinine clearance r=0.33, p=0.01; Cystatin C r=-0.30, p=0.003) and higher renal diuretic delivery was noted. Renal urea handling had the strongest correlation with renal diuretic delivery (fractional excretion of urea r=0.49, p= Conclusion Large variations IV loop diuretic delivered to the tubular site of action exists between hospitalized ADHF patients, and these differences relate to the ultimate diuretic response. The strongest associated factor is renal urea handling, which captures elements of renal perfusion, filtration, and solute handling. Given that patients with poor diuretic delivery may preferentially respond to loop diuretic titration, additional research is warranted to better identify patients with poor diuretic delivery.