Rising Serum Digoxin without Further Dosage in Acute Renal Failure

Abstract

A 73-year-old man was given a total of 1 mg of digoxin intravenously over 3 days, close to the time that he developed acute renal failure with oligo-anuria. He received no cardiac glycosides before or after this 3-day period. 2 days after the last dose, the serum digoxin concentration (SDC) was 2.9 ng/ml, yet a peak value of 4.2 ng/ml was reached only 11 days later. The SDC remained above 2 ng/ml for another week, until urine output began to increase appreciably. As renal function improved, the SDC gradually fell to become undetectable 32 days after the last dose. Values for apparent volume of distribution calculated from the total dose, and also determined after injection of tritiated digoxin, suggest that the rise in SDC in the absence of additional doses was due in large part to a decrease in the apparent volume of distribution. Dosage and parameters of toxicity should be carefully monitored in patients receiving digoxin who develop acute renal failure.

Deglycosylated Products of Endogenous Digoxin-like Immunoreactive Factor in Mammalian Tissue

“…The individual isoforms of Na,K-ATPase have been shown to possess differing affinities for binding of digitalis, ouabain, and their respective deglycosylated derivatives (11,12). The importance of characterizing the molecular and physical properties of DLIF is further underscored by the linkage observed between increased DLIF concentrations in blood and clinical or pathological conditions associated with altered ion-transport homeostasis such as: renal failure (13,14), hepatic failure (15), pregnancy (16), neonatal development (17,18), diabetes-and exercise-induced stress (19,20), and hypertension (21)(22)(23). The source of digitalis-like factors in a hormone-secreting tissue such as the adrenal, presence in blood, and the distribution of likely receptors in target tissues suggest the likely possibility of a new hormonal axis linking the adrenal cortex, endogenous digitalis-or ouabain-like factors, and sodium pump activity (5,24).…”

False-Positive Digoxin Measurements due to Conjugated Metabolite Accumulation in Combined Renal and Hepatic Dysfunction

“…Explanations considered and excluded at the time included medication error, sur reptitious ingestion or assay interference by a concomi tant drug. Based on previous reports, assay interference by an endogenous digoxin-like immunoreactive sub stance^) [ 1 ] and/or a decrease in the volume of distribu tion of digoxin due to diminished tissue uptake in pro gressive renal dysfunction [3,7] were considered the most likely explanations. An endogenous immunoreac tive substance(s) has been noted in similar patients but usually has accounted for less than 2 ng/ml o f 'apparent' digoxin [1,8], Our patient had increases in 'apparent' digoxin of almost double the greatest value previously reported.…”

“…Recent reports [2,3] have noted marked increases in serum digoxin concentration despite discontinuation of the drug in two patients with acute renal failure. An alteration in the volume of distribution of digoxin has been suggested to be the cause in one of these patients [3], Herein we describe a patient with renal and hepatic dysfunction in whom a marked increase in apparent serum digoxin concentration was observed despite dis continuation of the drug. This increase (peak value 8.6 ng/ml), however, was not associated with electrocardio graphic findings consistent with increased digoxin effect or toxicity.…”

“…ranging from 0.1 to 2.0 ng/ml, has been described in the serum of patients with renal or hepatic failure as well as in neonates and pregnant women in their third trimester [1]. Recent reports [2,3] have noted marked increases in serum digoxin concentration despite discontinuation of the drug in two patients with acute renal failure. An alteration in the volume of distribution of digoxin has been suggested to be the cause in one of these patients [3], Herein we describe a patient with renal and hepatic dysfunction in whom a marked increase in apparent serum digoxin concentration was observed despite dis continuation of the drug.…”

Endogenous Digoxin-Like Substance(s) Associated with Uneventful and High-Risk Pregnancies

“…Endogenous digoxin-like substance(s) (EDLS) detectable by radioimmunoassay for digoxin have been found in the serum of neonates [16,19], in patients with renal dis ease [6,8] and in essential hypertensives [4], In all cases the subjects shown to have EDLS circulating had not previously been exposed to digoxin or to any other cardiac glycoside. High EDLS levels have also been Previous studies have suggested that EDLS levels in the neonate stem from en dogenous production (secretion) of these as yet unidentified compounds [17], In the present series we wished to assess whether the course of late pregnancy affected neona tal EDLS levels.…”