Response to furosemide in chronic renal insufficiency: rationale for limited doses

Patients with renal insufficiency often undergo therapy with large doses of loop diuretics. We tested the hypotheses that remaining nephrons respond normally to amounts of diuretic reaching them, and that more limited doses than are commonly used are sufficient to reach effective portions of the dose-response curve. In eight patients with creatinine clearance less than 20 ml/min/1.73 m2, the amount of diuretic causing half-maximal response was identical to that in normal subjects, but the maximal response expressed as fractional excretion of sodium was increased approximately 60%. The upper plateau of the dose-response curve was attained with single intravenous doses of furosemide, 120 to 160 mg. In conclusion, remnant nephrons appear to demonstrate an exaggerated response to furosemide. Because maximal response was attained with single intravenous doses of furosemide of 120 to 160 mg, there appears to be no need to administer larger single doses in such patients.