The Effect of Furosemide on Residual Nephrons of the Chronically Diseased Kidney in Man

Abstract

Clearance studies were performed in 50 patients with varying degrees of stable chronic renal disease and 13 normal subjects in order to determine the effect of intravenous furosemide on residual nephrons of the chronically diseased kidney compared to nephrons within normal kidneys. Expression of data in terms of fractional excretion and excretion rate factored by GFR allows an analysis of furosemide effect as related to nephron population, in addition to an assessment of the absolute effect of this drug in producing a negative sodium, water, and potassium balance. A 0.25 mg/kg dose of furosemide produced virtually the same increment in the excretion rate per 100 ml GFR of sodium, water and potassium in diseased kidneys as in those of normal subjects until the GFR approached 15 ml/min. Thereafter, increments in sodium and water excretion were reduced out of proportion to the reduction in nephron mass, but were restored to a range comparable to normal by a 1 mg/kg dose. Studies in transplant donors before and after nephrectomy suggested that the increase in absolute sodium reabsorption which accompanies an increase in GFR per nephron does not explain the decreased responsiveness to the 0.25 mg/kg dose of furosemide observed in advanced azotemia. Thus, until severe disease supervenes with associated advanced azotemia, residual nephrons of the chronically diseased kidney retain responsiveness to a moderate dose of furosemide. The decrease in responsiveness per nephron observed in the presence of severe disease can be restored to normal levels by a 1 mg/kg dose of furosemide and appears to be more closely related to the presence of advanced azotemia rather than to other variables studied.