High Furosemide Dosage May Harm Kidneys

DALLAS—Halving the dosage of furosemide in patients with stable class II/III systolic heart failure and impaired renal function may improve glomerular filtration rate (GFR), according to data from a pilot study presented at the Heart Association's Scientific Sessions 2013.

Furosemide and other loop diuretics are mainstays in the medical management of heart failure. Although they have a class I indication, the level of evidence is C, which suggests that loop diuretics have not been extensively studied, said Paul McKie, MD, the study's lead investigator. “Preliminary data have shown that aggressive loop diuretics may adversely activate neurohumoral pathways and ultimately impair renal blood flow and decrease GFR,” he said. GFR is an important prognostic marker for cardiovascular morbidity and mortality in heart failure.

Thirty-two patients were enrolled in the National Institutes of Health-sponsored study, 19 with normal GFR (above 60 mL/min/1.72 m2) and 13 with reduced GFR (60 mL/min/1.72 m2 below).

Patients were monitored for at least three weeks prior to enrollment to ensure clinical stability on a stable dosage of furosemide. After three weeks, they underwent a comprehensive baseline assessment that included measurements of GFR and renal plasma flow, hemodynamic assessments, and assessment of functional capacity. After baseline assessment, individuals decreased their furosemide dosage by half. After three weeks they underwent the same assessments as at baseline.

Compared with patients who had normal renal function, those with reduced GFR were older (mean age 68 vs. 76 years), were taking higher doses of furosemide (103 vs. 119 mg/wk), used ACE inhibitors/angiotensin receptor blockers less often (92% vs. 68%), and had greater use of nitrates and hydralazine (15% vs. 37%), consistent with renal insufficiency.

The mean daily furosemide dosage at baseline was 38 and 36 mg in the reduced and normal renal function cohorts, respectively. During the three weeks of reduced furosemide, dosing the mean daily dose was 21 and 20 mg in reduced and normal renal function cohorts, respectively.

“There is a differential renal response to furosemide reduction according to baseline GFR,” said Dr. McKie, a cardiologist at the Mayo Clinic in Rochester, Minn.

Following three weeks of reduced furosemide dosing, GFR increased significantly from 42 to 51 mL/min/1.72 m2 in the reduced renal function cohort, with a trend toward an increase in renal plasma flow. GFR and renal plasma flow were not changed in the normal renal function cohort. A significant increase in the level of atrial natriuretic peptide and a strong trend toward an increase in cyclic guanosine monophosphate also occurred after halving the furosemide dose in the reduced GFR group but not in the group with normal renal function.

Results showed no change in activation of the renin-angiotensin-aldosterone system by lowering the dosages of furosemide nor were there changes in blood pressure or heart rate.

Reduction in furosemide did not adversely impact six-minute walk distance or the Minnesota Living with heart Failure Questionnaire score in either cohort. There were no adverse events or change in weight in either group.

“It's tempting to speculate that increased dosage of furosemide may reduce GFR in the setting of underlying renal insufficiency,” Dr. McKie said. Further studies are warranted to determine if these physiological findings would translate into improved clinical outcomes.

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