LAUSR

BACKGROUND The concept of multi-nephron segment diuretic therapy (MSDT) has been recommended in severe diuretic resistance (DR) with only expert opinion and case-level evidence. The purpose of this study was to investigate the safety and efficacy of MSDT, combining four diuretic classes, in acute heart failure (AHF) complicated by DR. METHODS A retrospective analysis was conducted in patients hospitalized with AHF at a single medical center who received MSDT, including concomitant carbonic anhydrase inhibitor, loop, thiazide, and mineralocorticoid receptor antagonist diuretics. Subjects served as their own controls with efficacy evaluated as urine output and weight change before and after MSDT. Serum chemistries, renal replacement therapies, and in-hospital mortality were evaluated for safety. Patients with Severe DR prior to MSDT were analyzed as a sub-cohort. RESULTS A total of 167 patients with AHF and DR received MSDT. MSDT was associated with increased median 24-hour urine output in the first day of therapy compared to the previous day (2.16 [0.95 - 4.14] liters to 3.08 [1.74 - 4.86] liters; p=0.003) in the total cohort and in the Severe DR cohort (0.91 [0.43 - 1.43] liters to 2.08 [1.13 - 3.96] liters, p<0.001). Median cumulative weight loss at Day 7 or discharge was -7.4 (-15.3 to -3.4) kg (p=0.02). Neither serum sodium, chloride, potassium, bicarbonate, or creatinine changed significantly relative to baseline (p>0.05 for all). CONCLUSIONS In an AHF cohort with diuretic resistance, MSDT was associated with increased diuresis without changes in serum chemistries or kidney function. Prospective studies of MSDT in AHF and diuretic resistance are warranted.