Volume Status and Diuretic Therapy in Systolic Heart Failure and the Detection of Early Abnormalities in Renal and Tubular Function

Objectives This study sought to determine the pharmacodynamic effect of modulation of volume status by withdrawal and reinstitution of diuretic treatment on markers of renal and tubular function. Background Decreased renal perfusion and increased congestion are associated with renal dysfunction in patients with heart failure. Methods In this study, 30 patients with chronic systolic heart failure in a presumed euvolemic state and on standard oral furosemide therapy (40 to 80 mg) were examined. At baseline, subjects were withdrawn from their loop diuretics. After 72 h, their furosemide regimen was reinstated, and patients were studied again 3 days later. Serum creatinine, atrial and B-type natriuretic peptide, urinary kidney injury molecule (KIM)-1, urinary N-acetyl-beta-D-glucosaminidase (NAG), and serum as well as urinary neutrophil gelatinase-associated lipocalin (NGAL) were determined at various time points. Results Diuretic withdrawal resulted in increases in atrial and B-type natriuretic peptide (both p < 0.05). Serum creatinine was unaffected. Both urinary KIM-1 (p < 0.001) and NAG (p < 0.010) concentrations rose significantly, after diuretic withdrawal, whereas serum and urinary NGAL were not significantly affected. After reinitiation of furosemide, both urinary KIM-1 and NAG concentrations returned to baseline (both p < 0.05), but NGAL values were unaffected. Conclusions Subclinical changes in volume status by diuretic withdrawal and reinstitution are associated with increases and decreases of markers of tubular dysfunction in stable heart failure. Diuretic therapy may favorably affect renal and tubular function by decreasing congestion. (J Am Coll Cardiol 2011;57:2233-41) (C) 2011 by the American College of Cardiology Foundation