The blunted loop diuretic response in acute heart failure is driven by reduced tubular responsiveness rather than insufficient tubular delivery. The role of furosemide urine excretion on diuretic and natriuretic response in acute heart failure

AimsDiuretic response in heart failure is blunted when compared to healthy individuals, but the pathophysiology underlying this phenomenon is unclear. We aimed to investigate whether the diuretic resistance mechanism is related to insufficient furosemide tubular delivery or low tubular responsiveness. Methods and resultsWe conducted a prospective, observational study of 50 patients with acute heart failure patients divided into two groups based on previous furosemide use (furosemide naive: n = 28 [56%] and chronic furosemide users: n = 22 [44%]). Each patient received a protocol-derived, standardized furosemide dose based on body weight. We measured diuretic response and urine furosemide concentrations. The furosemide naive group had significantly higher urine volumes and natriuresis when compared to chronic users at all timepoints (all p < 0.05). Urine furosemide delivery was similar in furosemide naive versus chronic users after accounting for differences in estimated glomerular filtration rate (28.02 [21.03-35.89] vs. 29.70 [18.19-34.71] mg, p = 0.87). However, the tubular response to delivered diuretic was dramatically higher in naive versus chronic users, that is the urine volume per 1 mu g/ml of urine furosemide at 2 h was 148.6 +/- 136.1 versus 50.6 +/- 56.1 ml (p = 0.005). ConclusionsPatients naive to furosemide have significantly better diuresis and natriuresis when compared to chronic furosemide users. The blunted diuretic response in patients with chronic loop diuretic exposure is driven by decreased tubular responsiveness rather than insufficient furosemide tubular delivery.