Volume Status and Diuretic Therapy in Systolic Heart Failure and the Detection of Early Abnormalities in Renal and Tubular Function
Does change in volume status induced by withdrawal and reinstitution of diuretic therapy impact markers of renal and tubular function in systolic heart failure (HF)?
This was a nonrandomized study of patients (n = 30) with chronic systolic HF (left ventricular ejection fraction <40%) on optimal medical management with oral diuretic requirements of 40-80 mg daily. Diuretic therapy was withdrawn for 48 hours and then 50 mg of intravenous furosemide was administered on day 3. The home oral diuretic regimen was reinstituted on day 4. Serum markers of HF (atrial natriuretic peptide [ANP] and B-type natriuretic peptide [BNP]) and markers of renal tubular function (urinary kidney injury molecule-1 [KIM-1], urinary N-acetyl-beta-D-glucosaminidase [NAG]) and renal function (creatinine) were measured at baseline and on all subsequent days.
The mean patient age was 70 ± 7 years, 87% were male, and 87% were New York Heart Association class II HF. Median (interquartile range) baseline creatinine was 1.7 (1.3-2.3) mg/dl, glomerular filtration rate 47 (27-54) ml/min/1.73 m2, and BNP 157 (104-292) pg/ml. During diuretic withdrawal, there was a nonsignificant 1.6 kg increase in body weight (p = 0.15). Serum creatinine did not change (p > 0.05). Both ANP (p < 0.05 within 4 hours of diuretic withdrawal) and BNP (p < 0.05 after 72 hours of diuretic withdrawal) increased compared to baseline. Urinary KIM-1 was significantly higher than baseline within 8 hours of diuretic withdrawal, peaking after 48 hours. Urinary NAG also peaked at 48 hours, but was slower to rise. After reinstitution of diuretic therapy, BNP, KIM-1, and urinary NAG levels returned to baseline values, but ANP continued to rise. Serum creatinine did not change.
The authors concluded that diuretics favorably impact renal tubular function by decreasing renal venous congestion.
Reduced renal blood flow secondary to high central venous pressures is thought to be a major contributor to renal dysfunction in HF. The authors discuss that KIM-1 and NAG are markers of renal proximal tubular injury and the increase in levels after diuretic withdrawal represents hypoxic tubular damage, which improves after diuretic reinstitution. While studies in patients with HF are divergent on the impact of diuretics on renal function, this study suggests that diuretics may improve renal function by reducing renal venous congestion. An editorial by Dr. Gottlieb follows this study, highlighting the unfilled gaps in our knowledge about the impact of diuretics in HF and on renal function. This is a thought-provoking study, but clear demonstration of changes in weight or central venous pressure with diuretic modulation would have strengthened the association. An explanation for the continued rise in ANP is also lacking.
Keywords: Biological Markers, Renal Circulation, Diuretics, Guanidines, Glomerular Filtration Rate, Kidney, Central Venous Pressure, New York, Heart Failure, Systolic, Furosemide, Atrial Natriuretic Factor
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