The question of cumulation of digoxin metabolites in renal failure

Using high-performance liquid chromatography (HPLC) to separate digoxin from its metabolites digoxigenin, digoxigenin-bis-digitoxoside, and digoxigenin-mono-digitoxoside with subsequent quantitation by 125I radioimmunoassay (RIA), we examined the plasma of patients on long-term oral digoxin therapy. Digoxin was also measured by RIA without prior HPLC separation. Nine patients requiring maintenance dialysis and 9 subjects with lesser degrees of renal impairment were studied. Trace amounts of 1 or more of the digoxin metabolites were found in the plasma of all dialysis patients while subjects with lesser degrees of renal failure had either none or only 1 metabolite in trace amounts. The ratio of HPLC digoxin without HPLC was 0.83 +/- 0.12 (SD) in renal failure patients and 1.06 +/- 0.09 in subjects with renal function (p less than 0.01). RIA overestimates the amount of digoxin in plasma of renal failure patients and in them from 6% to 42% of plasma digoxin, as determined by conventional 125I RIA, may represent compounds other than digoxin.