Renal response to intravascular volume expansion in euvolemic heart failure patients with reduced ejection fraction: Mechanistic insights and clinical implications

Abstract

BackgroundUntreated and preclinical heart failure patients with reduced ejection fraction (HFrEF) have an impaired ability to alleviate excess intravascular volume. ObjectivesTo investigate 1) the renal response to intravascular volume expansion in euvolemic and optimally treated HFrEF patients and 2) loop diuretic efficiency. Methods14 healthy and 28 HFrEF patients underwent intravascular volume expansion with 1l hydroxyl ethyl starch 6% during 3h after which a loop diuretic was administered. Clinical parameters, neurohormones and urine were hourly measured. ResultsIn response to intravascular volume expansion (+0.6±0.2L; p<0.001 vs baseline) HFrEF patients demonstrated significantly lower natriuresis compared to healthy subjects (0.9±0.5 versus 1.7±0.6g/3h; p<0.001). However, natriuresis varied substantially with half of HFrEF patients exhibiting a response within the range of healthy and the other half demonstrating a significantly decreased response (1.4±0.4 vs 0.5±0.2g/3h; p<0.001). Natriuresis was associated with glomerular filtration function (eGFR), NT-proBNP and tubular fractional sodium excretion (FENa). Loop diuretic efficiency was significantly lower in HFrEF patients compared to healthy subjects (3.4±0.7 vs 2.6±1.1g/2h; p=0.044) but was only related to eGFR (R2=0.47; p<0.001) and independent of FENa (R2=0.07; p=0.20). Loop diuretics increased FENa similarly in healthy subjects and HFrEF patients (9.1±2.4 vs 9.3±3.3%; p=0.64). ConclusionThe ability of the kidneys to remove excess intravascular volume is decreased in a substantial amount of euvolemic and optimally treated HFrEF patients. Renal response relates to filtration function and tubular sodium handling. In contrast, loop diuretics can surmount decreased renal tubular sodium excretion but remain dependent on eGFR.