Renal clearance of digoxin in man after sodium loading or furosemide treatment

To evaluate the influence of different types of natriuresis on the renal clearance of digoxin (Cldig) and the Cldig/Clcr ratio, studies were performed in which sodium-depleted patients were placed on a moderately high sodium diet for 6 days. In another group natriuresis was evoked by furosemide. In the first study, in 10 patients, there was a 10-fold increase in Na excretion and a small rise in diuresis (V) and Clcr, which was accompanied by an increase in Cldig from 57.5 +/- 32, and 60.7 +/- 27.3 (duplicate measurements) to 103.9 +/- 55.4 (p less than 0.01) and 103.8 +/- 46.5 ml min-1 (p less than 0.01). Cldig/Clcr rose from 0.60 +/- 0.24 and 0.61 +/- 0.16 to 0.91 +/- 0.31 and 0.91 +/- 0.21, respectively (both p less than 0.005). Serum digoxin concentration declined from 1.24 +/- 0.35 and 1.19 +/- 0.40 to 1.02 +/- 0.35 and 0.97 +/- 0.32 micrograms/l (both p less than 0.01) during the high sodium diet. In the furosemide-induced natriuresis (6 patients), changes in Na excretion and V were a multiple of those caused by Na loading, but the Cldig/Clcr ratio was not increased. The results are in accordance with the concept of digoxin backdiffusion in the proximal tubules, which is dependent on proximal Na reabsorption. In the more distal segments of the nephron, where the action of furosemide occurs, there does not appear to be any transtubular movement of digoxin.