digoxin and Renal-Insufficiency

Digoxin reduces hospitalizations due to heart failure (HF) and may also reduce mortality at low serum digoxin concentrations (SDC). Most HF patients are > or = 65 years, yet the effects of digoxin on outcomes in these patients have not been well studied.. Of the 7788 ambulatory chronic HF patients in normal sinus rhythm in the Digitalis Investigation Group trial (1991-1995), 5548 (2890 were > or = 65 years) were alive at 1 month and were either receiving placebo or had data on SDC. Of these patients, 982 had low (0.5-0.9 ng/mL) and 705 had high (> or = 1 ng/mL) SDC.. Among patients > or = 65 years, compared with 38% placebo patients, 34% low SDC patients died during 39 months of median follow-up (adjusted hazard ratio [AHR] = 0.81; 95% confidence interval [CI] = 0.68-0.96; p =.017). All-cause hospitalizations occurred in 70% of placebo and 68% of low-SDC patients (AHR = 0.86; 95% CI = 0.76-0.98; p =.019). Reduction in hospitalizations for HF occurred in both low and high SDC groups. High SDC was not independently associated with all-cause hospitalization or all-cause mortality. Age, impaired renal function, and pulmonary congestion reduced the odds of low SDC. Low-dose digoxin (< or = 0.125 mg/d) was the strongest independent predictor of low SDC (adjusted odd ratio = 2.37; 95% CI = 1.65-3.39); p <.0001).. Digoxin at low SDC was associated with a reduction in mortality and hospitalization in chronic geriatric HF, and low-dose digoxin was the strongest predictor of low SDC.

Topics: Age Factors; Aged; Canada; Cardiac Output, Low; Cardiotonic Agents; Chronic Disease; Creatinine; Digoxin; Diuretics; Female; Follow-Up Studies; Hospitalization; Humans; Male; Middle Aged; Placebos; Pulmonary Edema; Renal Insufficiency; Survival Rate; Treatment Outcome; United States

Renal dysfunction is a common complication for patients with heart failure, but its association with clinical outcomes has not been fully characterized. We evaluated the association of glomerular filtration rate (GFR) with heart failure survival and the effect of digoxin on heart failure outcomes across GFR strata. A secondary analysis from the Digitalis Intervention Group trial was conducted of 6800 outpatients with systolic heart failure. Renal function was categorized as estimated GFR (expressed in ml/min per 1.73 m(2)). All-cause mortality (mean, 3 yr) was inversely proportional to GFR (GFR >60, 31% mortality; GFR 30 to 60, 46% mortality; GFR <30, 62% mortality; P < 0.001). Among patients with a GFR <50, lower GFR were associated with greater adjusted mortality risk (GFR <30: hazard ratio [HR], 2.06, 95% confidence interval [CI], 1.69 to 2.51; GFR 30 to 40: HR, 1.42, 95% CI, 1.22 to 1.67; GFR 40 to 50: HR, 1.22, 95% CI, 1.07 to 1.39; GFR 50 to 60: HR, 1.00, referent). In contrast, participants with GFR 60 to 70 had similar risk (HR, 1.00; 95% CI, 0.88 to 1.14) compared with GFR 50 to 60, and those with GFR >70 had a slightly lower mortality hazard (0.89; 95% CI, 0.78 to 1.00). Linear spline analyses confirmed that GFR = 50 was the appropriate risk threshold; above 50, GFR had no association with mortality, whereas below 50, mortality risk increased sharply with declining GFR (spline coefficient, P < 0.0001). Digoxin efficacy did not differ by level of GFR (P = 0.19 for interaction). Renal dysfunction is strongly associated with mortality in stable outpatients with heart failure, notably in patients with estimated GFR <50 ml/min per 1.73 m(2). The effect of digoxin did not differ by level of renal function.

Topics: Aged; Cardiotonic Agents; Cohort Studies; Digoxin; Female; Glomerular Filtration Rate; Heart Failure; Humans; Kidney; Male; Middle Aged; Renal Insufficiency; Risk Factors; Survival Analysis

Despite being the oldest therapy for heart failure, the use of digoxin is still controversial due to the narrow margin of safety. In Indonesia, digoxin is still considered one of the treatments for heart failure. However, analysis of intoxication has never been reported. This study aims to analyze the occurrence of digoxin intoxication, rate of rehospitalization and one-year survival in heart failure patients under digoxin treatment.. A cross section-observational study was conducted at Harapan Kita National Cardiovascular Centre from January 2017 to December 2018 on heart failure patients who received digoxin therapy and had data on serum digoxin level. Intoxication was defined as the presence of specific ECG alteration(s), at least one extra-cardiac symptom(s) and further classified as definite (serum digoxin >2 ng/mL), probable (serum digoxin 0.91-1.99 ng/mL), or possible (serum digoxin 0.5-0.9 ng/mL). Risk factors of intoxication were analyzed by Chi-square test, and one-year survival was analyzed with Kaplan Meyer method.. 54 of 195 patients (27.69%) were classified as having intoxication, consisting of 32 (16.41%) definite, 19 (9.74%) probable, and 3 (1.54%) possible. Renal insufficiency was revealed as a significant influencing factor of digoxin intoxication with RR 2.48 (CI 1.13-5.464, p=0.016). Overall one-year survival of patients receiving digoxin was 259 days in the intoxication group and 307 days in the non-intoxication group. One-year rehospitalization was 11.8% in patients who received digoxin and 29.2% in those without digoxin (p=0.085).. The proportion of digoxin intoxication in heart failure patients was 27.69%. Renal insufficiency was revealed as a significant influencing factor of intoxication. There was a tendency of reduced hospitalization in those who received digoxin.

Topics: Digoxin; Disease Progression; Heart Failure; Humans; Indonesia; Patient Readmission; Renal Insufficiency

We describe the case of a patient on continuous venovenous hemodiafiltration with atrial fibrillation with rapid ventricular response and hypotension requiring vasopressor use, which warranted digoxin therapy. In the absence of guidelines specifying appropriate digoxin dosing in patients undergoing continuous venovenous hemodiafiltration, anecdotal evidence-guided digoxin dosing was performed for this patient using plasma digoxin concentration-based therapeutic drug monitoring. We use this case to demonstrate the potential role of physiologically based pharmacokinetic modeling in assisting therapeutic decision making.

Topics: Aged; Atrial Fibrillation; Body Weight; Cardiotonic Agents; Continuous Renal Replacement Therapy; Digoxin; Drug Dosage Calculations; Drug Monitoring; Hemodiafiltration; Humans; Hypotension; Kidney Function Tests; Male; Models, Biological; Point-of-Care Systems; Renal Insufficiency

Treatment of chronic digitalis intoxication includes suspension of drug intake, which may be sufficient in case of mild manifestations, and supportive measures. Severe bradycardia requires the administration of atropine or isoproterenol; placement of a temporary pacemaker may be required in case of absent response to pharmacological therapy. Severe and life-threatening manifestations should be treated with digoxin-specific fragment antigen binding antibodies (Fab). Therapeutic plasma exchange has been suggested, in addition to Fab therapy, to maximize the clearance of Fab-digoxin complexes in patients with renal failure. To date, few case reports have described the use of such a therapeutic approach; currently, extracorporeal methods are not recommended as part of the treatment of digitalis intoxication, and stronger evidence is required to establish their benefit.

Topics: Aged; Bradycardia; Digoxin; Female; Humans; Immunoglobulin Fab Fragments; Metabolic Clearance Rate; Plasma Exchange; Poisoning; Renal Insufficiency

Drug-drug interactions with corticosteroids, causing Cushing's syndrome with secondary adrenal suppression, are well known in HIV patients. Corticosteroids are widely prescribed in the HIV-positive population. However, digoxin is rarely used in HIV patients; hence, digoxin toxicity due to drug-drug interaction is not widely recognised. Nevertheless, this practice might change in the future as HIV cohorts of patients are ageing, due to the successful treatment of HIV infection with combination antiretroviral therapy. We report a case of digoxin toxicity in an HIV-positive 51-year-old man, due to a combination of drug-drug interaction and renal impairment. The first case report of digoxin toxicity due to drug-drug interaction with ritonavir in an HIV-positive woman was published in 2003. To the best of our knowledge, no similar case report has since been published in the literature. This case alerts the profession to the importance of drug-drug interaction and highlights the clinical features of digoxin toxicity.

Topics: Darunavir; Digoxin; Drug Interactions; HIV Infections; HIV Protease Inhibitors; Humans; Male; Middle Aged; Renal Insufficiency; Ritonavir

Topics: ATP Binding Cassette Transporter, Subfamily B, Member 1; Digoxin; Glomerular Filtration Rate; Humans; Kidney; Metabolic Clearance Rate; Models, Biological; Organic Anion Transporters; Renal Elimination; Renal Insufficiency

The aim of this study was to assess temporal trends and factors associated with digoxin use at discharge among patients admitted with heart failure (HF).. Digoxin has class IIa recommendations for treating HF with reduced ejection fraction (HFrEF) in the United States. Digoxin use, temporal trends, and clinical characteristics of HF patients in current clinical practice in the United States have not been well studied.. An observational analysis of 255,901 patients hospitalized with HF (117,761 with HFrEF and 138,140 with preserved EF [HFpEF]) from 398 hospitals participating in the Get With The Guidelines-HF registry between January 2005 and June 2014 was conducted to assess the temporal trends and factors associated with digoxin use.. Among 117,761 HFrEF patients, only 19.7% received digoxin at discharge. Digoxin prescriptions decreased from 33.1% in 2005 to 10.7% in 2014 (ptrend < 0.0001). Factors associated with digoxin use in HFrEF included atrial fibrillation (AF) (odds ratio [OR]: 2.14; 95% confidence intervals [CI]: 2.02 to 2.28), history of implantable cardioverter defibrillator use (OR: 1.39; 95% CI: 1.32 to 1.46), chronic obstructive pulmonary disease (OR: 1.13, 95% CI: 1.08 to 1.18), diabetes mellitus (OR: 1.10, 95% CI: 1.06 to 1.14), younger age (OR: 0.96, 95% CI: 0.95 to 0.97), lower blood pressure (OR: 0.96, 95% CI: 0.96 to 0.97), and having no history of renal insufficiency (OR: 0.91, 95% CI: 0.85 to 0.97). Use of digoxin in patients with HFpEF (n = 138,140) without AF was 9.8% in 2005, which decreased to 2.2% in 2014 (ptrend < 0.0001).. One in 5 HFrEF patients received digoxin at discharge, with a significant downward temporal trend in use over the study period. Use of digoxin in HFpEF patients without AF was very low and decreased over the study period.

Topics: Age Factors; Aged; American Heart Association; Atrial Fibrillation; Blood Pressure; Cardiotonic Agents; Comorbidity; Defibrillators, Implantable; Diabetes Mellitus; Digoxin; Female; Heart Failure; Hospitalization; Humans; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Practice Patterns, Physicians'; Pulmonary Disease, Chronic Obstructive; Registries; Renal Insufficiency; Stroke Volume; United States

Topics: Anti-Arrhythmia Agents; Digoxin; Female; Glomerular Filtration Rate; Humans; Male; Renal Insufficiency

Although the possible interference of digoxin-like immunoreactive substances (DLIS) on the Architect iDigoxin chemiluminiscent microparticle immunoassay (CMIA) has been emphasized by the manufacturer, a specific study about this subject has still not been carried out.. Apparent serum digoxin concentrations were determined using the Architect iDigoxin CMIA from Abbott Laboratories in digoxin-free pregnant women (n = 50), and patients with liver disease (n = 50), renal insufficiency (n = 50), kidney (n = 25) or liver (n = 25) transplant, and critical illness (n = 50).. In all of the patients included in this study, apparent serum digoxin concentrations were lower than the correspondent quantification limit (< 0.30 microg/L).. The Architect iDigoxin CMIA assay would be relatively free from endogenous DLIS positive interferences.

Topics: Adult; Aged; Aged, 80 and over; Critical Illness; Digoxin; Female; Humans; Kidney Transplantation; Liver Diseases; Liver Transplantation; Male; Middle Aged; Pregnancy; Renal Insufficiency

Renal function decreases with age. Dosage adjustment according to renal function is indicated for many drugs, in order to avoid adverse reactions of medications and/or aggravation of renal impairment. There are several ways to assess renal function in the elderly, but no way is ideal. The aim of the study was to explore renal function in elderly subjects in nursing homes and the use of pharmaceuticals that may be harmful to patients with renal impairment.. 243 elderly subjects living in nursing homes were included. S-creatinine and s-cystatin c were analysed. Renal function was estimated using Cockcroft-Gault formula, Modification of Diet in Renal Disease (MDRD) and cystatin C-estimated glomerular filtration rate (GFR). Concomitant medication was registered and four groups of renal risk drugs were identified: metformin, nonsteroidal anti-inflammatory drugs (NSAID), angiotensin-converting enzyme -inhibitors/angiotensin receptor blockers and digoxin. Descriptive statistics and the Kappa test for concordance were used.. Reduced renal function (cystatin C-estimated GFR < 60 ml/min) was seen in 53%. Normal s-creatinine was seen in 41% of those with renal impairment. Renal risk drugs were rather rarely prescribed, with exception for ACE-inhibitors. Poor concordance was seen between the GFR estimates as concluded by other studies.. The physician has to be observant on renal function when prescribing medications to the elderly patient and not only rely on s-creatinine level. GFR has to be estimated before prescribing renal risk drugs, but using different estimates may give divergence in the results.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Anti-Arrhythmia Agents; Anti-Inflammatory Agents, Non-Steroidal; Cohort Studies; Comorbidity; Creatinine; Cystatin C; Digoxin; Female; Geriatric Assessment; Glomerular Filtration Rate; Humans; Kidney; Kidney Function Tests; Male; Nursing Homes; Renal Insufficiency

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Digoxin; Drug Overdose; Female; Glomerular Filtration Rate; Humans; Kidney Function Tests; Male; Renal Insufficiency; Retrospective Studies; Risk Assessment; ROC Curve

We present the case of a 75-year-old patient admitted to the emergency department after ingesting a large amount of several cardiac drugs, among which were digoxin and sotalol. Because of renal insufficiency, cardiogenic shock, and high serum digoxin levels, the patient received continuous venovenous hemofiltration (CVVH) and digoxin-specific Fab fragments. Digoxin and the digoxin-specific Fab fragments are normally cleared by the kidneys.. Serum-free and total digoxin and serum sotalol concentrations were monitored for several days.. Less than 10% of the estimated ingested dose of digoxin was cleared by CVVH within 5 days.. CVVH has little influence on the clearance of Fab-bound digoxin from the body. In contrast, sotalol is efficiently cleared by CVVH.

Topics: Aged; Anti-Arrhythmia Agents; Digoxin; Hemofiltration; Humans; Immunoglobulin Fab Fragments; Male; Renal Insufficiency; Shock, Cardiogenic; Sotalol; Time Factors

In the case of severe digoxin intoxication, an antidote digoxin immune Fab (Digibind) is available. Digibind binds and inactivates digoxin. Measuring se-digoxin after administering Digibind (by standard measuring methods) is misleading as Digibind interferes with digitalis immunoassay measurements. The effect of Digibind must be estimated on the basis of the disappearance of the patient's symptoms and cardiac abnormalities. A case involving Fab therapy of a digoxin-overdosed patient is reported.

Topics: Aged; Anti-Arrhythmia Agents; Aortic Aneurysm, Abdominal; Digoxin; Drug Overdose; Humans; Immunoglobulin Fab Fragments; Male; Postoperative Complications; Renal Insufficiency

Digoxin (DX) is mainly excreted unchanged in the urine. In patients undergoing hemodialysis (HD patients), the relative contribution of hepatic elimination is increased. DX is a substrate of OATP1B3 (SLCO1B3), expressed on the sinusoidal membranes of hepatocytes in humans. Therefore, we investigated the relationship between SLCO1B3 gene polymorphisms and the value of trough concentration-to-dose ratio (C/D ratio) of DX in HD patients. We investigated two deletion polymorphisms in complete linkage disequilibrium (-28 to -11 and -7 to -4) and two SNPs in complete linkage disequilibrium (T334G and G699A). Blood was sampled 62-72 hours after the oral administration of DX. The C/D ratio of DX was lower in patients with the deletion allele than in those homozygous for the insertion allele, and was lower in patients with the 334T/669G allele than in those homozygous for the 334G/699A allele, although the differences were not statistically significant. The C/D ratio of DX was significantly higher in patients with homozygous for the insert-variant allele (median: 121.8 (ng/mL)/(mg/week/kg), range: 92.5-259.4 (ng/mL)/(mg/week/kg) than in others (median: 93.4 (ng/mL)/(mg/week/kg), range: 66.5-154.3 (ng/mL)/(mg/week/kg)). In conclusion, the insert-variant allele of the OATP1B3 gene may increase the C/D ratio of DX in HD patients.

Topics: Digoxin; Dose-Response Relationship, Drug; Female; Gene Frequency; Genetic Variation; Genotype; Humans; Male; Mutagenesis, Insertional; Organic Anion Transporters, Sodium-Independent; Polymorphism, Genetic; Renal Insufficiency; Solute Carrier Organic Anion Transporter Family Member 1B3

Pentosidine, one of the advanced glycation end products (AGE), is generated by nonenzymatic glycation and oxidation of proteins. The receptor of AGE (RAGE) is expressed in a variety of tissue, and interaction of AGE with RAGE induces oxidative stress and activation of intracellular signaling, causing production of cytokines and mediators of inflammation. We investigated whether serum pentosidine is a risk factor for heart failure.. Serum pentosidine concentration was measured in 141 patients with heart failure and 18 control subjects by a competitive enzyme-linked immunosorbent assay. Patients were prospectively followed during a median follow-up period of 479 days with end points of cardiac death or rehospitalization. Serum concentration of pentosidine was significantly higher in New York Heart Association (NYHA) Class III/IV patients than in NYHA class I/II patients (P < .0001). Serum pentosidine was also higher in patients with cardiac events than in event-free patients (P < .001). In the univariate Cox proportional hazard analysis, age, NYHA class, pentosidine, creatinine, uric acid, B-type natriuretic peptide, left ventricular end-systolic volume, and left ventricular mass were significant risk factors to predict cardiac events. In the multivariate Cox analysis, serum pentosidine concentration was an independent risk factor for cardiac events (hazard ratio 1.88, 95% confidence interval 1.23-2.69, P = .002). The highest 4th quartile of pentosidine was associated with the highest risk of cardiac events (4.52-fold).. Serum pentosidine concentration is an independent prognostic factor for heart failure, and this new marker may be useful for risk stratification of patients with heart failure. Patients were divided into 4 groups based on the serum pentosidine levels.

Topics: Aged; Arginine; Biomarkers; Cardiotonic Agents; Case-Control Studies; Comorbidity; Diabetes Complications; Digoxin; Diuretics; Female; Follow-Up Studies; Heart Failure; Hospitalization; Humans; Japan; Lysine; Male; Middle Aged; Multivariate Analysis; Prognosis; Proportional Hazards Models; Prospective Studies; Renal Insufficiency; Risk Factors; Sensitivity and Specificity; Severity of Illness Index; Survival Analysis

Reduced renal function requires dose adjustment for certain drugs to avoid toxicity. The aim of this study was to determine whether appropriate dosage adjustments were made for drugs that are nephrotoxic, excreted, or metabolized (TEM medications) by the kidney in patients with renal impairment.. A cross-sectional study of a group of hospitalized patients was carried out at Al-Watni governmental hospital, Nablus, Palestine. All patients with creatinine clearance

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Creatinine; Cross-Sectional Studies; Digoxin; Drug-Related Side Effects and Adverse Reactions; Female; Hospital Bed Capacity, 100 to 299; Hospitals, Public; Humans; Israel; Male; Medication Errors; Middle Aged; Models, Statistical; Pharmaceutical Preparations; Pharmacokinetics; Ranitidine; Renal Insufficiency

Digoxin, which is one of the most commonly prescribed drugs for the treatment of heart failure, is mainly eliminated from the circulation by the kidney. P-glycoprotein is well characterized as a digoxin pump at the apical membrane of the nephron. However, little is known about the transport mechanism at the basolateral membrane. We have isolated an organic anion transporter (OATP4C1) from human kidney. Human OATP4C1 is the first member of the organic anion transporting polypeptide (OATP) family expressed in human kidney. The isolated cDNA encodes a polypeptide of 724 aa with 12 transmembrane domains. The genomic organization consists of 13 exons located on chromosome 5q21. Its rat counterpart, Oatp4c1, is also isolated from rat kidney. Human OATP4C1 transports cardiac glycosides (digoxin, K(m) = 7.8 microM and ouabain, K(m) = 0.38 microM), thyroid hormone (triiodothyronine, K(m) = 5.9 microM and thyroxine), cAMP, and methotrexate in a sodium-independent manner. Rat Oatp4c1 also transports digoxin (K(m) = 8.0 microM) and triiodothyronine (K(m) = 1.9 microM). Immunohistochemical analysis reveals that rat Oatp4c1 protein is localized at the basolateral membrane of the proximal tubule cell in the kidney. These data suggest that human OATP4C1/rat Oatp4c1 might be a first step of the transport pathway of digoxin and various compounds into urine in the kidney.

Topics: Amino Acid Sequence; Animals; Base Sequence; Cell Line; Cloning, Molecular; Digoxin; DNA, Complementary; Dogs; Female; Humans; Kidney; Kinetics; Male; Molecular Sequence Data; Organic Anion Transporters; Phylogeny; Rats; Recombinant Proteins; Renal Insufficiency; RNA, Messenger; Sequence Homology, Amino Acid; Tissue Distribution; Transfection

To evaluate three methods for digoxin dose adjustment in aged patients.. We determined the plasma digoxin levels that would be attained in 87 old patients with doses adjusted to the kidney function by means of three separate procedures.. Age: 79.0 "6.3 years of age; creatinin clearance (Clc): 0.70" 0.23 ml/Kg of lean body weight and minute. Only the methods that adjust both the digoxin clearance and the volume of distribution to the Clc achieve the independence between the digoxinemia and the kidney function. The best of them, by calculating the elimination constant (K) and the volume of distribution (V) as linear functions of the Clc, so that K ranges between 0.173 and 0.462 days-1 and V between 4 and 10 l/Kg of lean body weight when the Clc varies from 0 to 110 ml/minute, achieve digoxinemia figures between 0.8 y 2.0 ng/ml and above 2.0 ng/ml in the 81.6% and 0.0% of the patients (95% confidence intervals (95% CI): 72.2% to 88.4 and 0.0% to 4.6%), respectively; with a precision and a bias of 0.43 and -0.06 ng/ml (95% CI: 0.38 to 0.48 and -0.16 to 0.03 ng/ml), respectively.. The described method would lead to good results if digoxin has not been prescribed in order to control the cardiac frequency in the setting of auricular fibrilation.

Topics: Aged; Aged, 80 and over; Anti-Arrhythmia Agents; Digoxin; Female; Humans; Kidney; Male; Renal Insufficiency

A new turbidimetric inhibition immunoassay for digoxin (Tina-quant [a] Digoxin, Boehringer Mannheim) was evaluated in seven laboratories. It can be performed without sample pretreatment with ready-to-use reagents on nondedicated analyzers in combination with routine clinical chemistry. The studies revealed a good analytical performance: lower limit of detection 0.12 microg/L (3 SD from mean of blank); linearity up to 7.5 microg/L; median between-run CVs 8.1% (0.6 microg/L), 2.8% (1.5 microg/L), 1.9% (3 microg/L); mean analytical recovery in control sera 98-102%; slopes from 0.97 to 1.09 and intercepts from -0.28 to 0.10 microg/L in comparison with four immunoassays; and a high resistance to common interferents. The test was more resistant to digoxin-like immunoreactive factor (DLIF) interference than other methods, showing cross-reactivity only in some intensive care patient samples. Among 192 patients in whom DLIF is expected (e.g., pregnant women, patients with renal failure, newborns), 90% of results were < or =0.26 microg/L digoxin. Cortisol showed no cross-reactivity and digoxigenin had a low reactivity. An interlaboratory survey revealed a good comparability of the Tina-quant [a] test with the median of all methods (slope 0.99, intercept -0.06 microg/L). An HPLC method for digoxin based on isocratic separation of samples on an RP-18 column followed by detection by an immunoassay yielded a reasonable comparability with the immunochemical tests with noncritical samples. Divergent results of immunoassays caused by DLIFs or different cross-reactivities with digoxin metabolites or derivatives can be explained by the use of this HPLC method.

Topics: Anticoagulants; Chromatography, High Pressure Liquid; Critical Care; Digoxin; Female; Humans; Immunoassay; Indicators and Reagents; Infant, Newborn; Laboratories; Nephelometry and Turbidimetry; Pregnancy; Quality Control; Reference Values; Renal Dialysis; Renal Insufficiency; Sensitivity and Specificity

To further define the chemical structure of human endogenous digoxinlike immunoreactive factors (DLIF) we used human pleural effusions as a source of the substance. Digoxinlike immunoreactive factor activity was detected by radioimmunoassay in the pleural fluid of each of four patients; average concentration was 0.35 ng/mL. The chemical profile of DLIF was determined by initial extraction and concentration of DLIF by ion exchange chromatography followed by reverse phase-high-pressure liquid chromatography (RP-HPLC) separation and purification. Using high-pressure liquid chromatography cochromatography of DLIF, together with several radioactively marked glycosides, we observed a single peak of DLIF activity that was chromatographically identical to digoxin. The present study further supports the recent finding that DLIF is related structurally to the cardiac glycosides, and for the first time it has been proven that DLIF is present in pleural fluids.

Topics: Cardenolides; Chromatography, High Pressure Liquid; Chromatography, Ion Exchange; Digoxin; Female; Humans; Lung Neoplasms; Male; Pleural Effusion; Renal Insufficiency; Saponins

To study the influence of age and renal function on digoxin-specific Fab (DS-Fab) pharmacokinetics.. Sixteen patients (35-91 years) with creatinine clearance ranging from 10.6 to 122.1 ml min(-1) who had been admitted to hospital with severe digoxin or digitoxin self-poisoning were treated with DS-Fab (80 to 800 mg). Plasma DS-Fab concentrations were determined by radioimmunoassay.. The mean (s.d.) distribution and elimination half-lives, apparent volume of distribution and total body clearance were 1.1 +/- 0.4 h, 20.2 +/- 7.3 h, 13.1 +/- 5.8 l, and 17.6 +/- 10.8 ml min(-1), respectively. Interindividual variability of DS-Fab total body clearance was linked linearly with the decrease in creatinine clearance or with the increase in age and DS-Fab distribution volume was not dependent on creatinine clearance or age.. The data suggest that DS-Fab should be given to elderly and renal-impaired patients at doses similar to those given to younger or normal renal function patients.

Topics: Adult; Aged; Aged, 80 and over; Aging; Area Under Curve; Digoxin; Female; Half-Life; Humans; Immunoglobulin Fab Fragments; Kidney; Male; Middle Aged; Renal Insufficiency; Tissue Distribution

We examined the specificity of three automated digoxin immunoassays (Abbott TDxFLx Digoxin II assay, Baxter-Dade Stratus II Digoxin assay, and Ciba Corning ACS Digoxin assay) applied without modification to (a) sera from 229 digoxin-free patients in 12 cohorts associated with nonspecific or endogenous digoxin-like immunoreactive factor (DLIF) interference, and (b) drug-free serum supplemented with the major metabolites and analogs of digoxin. We observed three patterns of apparent digoxin results among the DLIF samples: one common to kidney and liver failure patients, where TDx and Stratus assays showed significant positive results; one common to newborns and cord blood, where only the TDx assay had significant interference; and one from cardiac surgery patients, where the Stratus assay alone showed interference. Of the three assays, the ACS had the least interference from DLIF. The assays also behaved differently with respect to cross-reactivity with digoxin metabolites, digitoxin, and digitoxin metabolites. The ACS assay again had the least analog or metabolite cross-reactivity. The three methods agreed well on digoxin-positive specimens, with a mean bias of <0.15 microgram/L digoxin for each and discrepancies (defined as >3 SD between the assay pairs compared) of only 3-5%.

Topics: Antibody Specificity; Autoanalysis; Blood Proteins; Cardenolides; Cohort Studies; Digoxin; Fetal Blood; Humans; Immunoassay; Infant, Newborn; Liver Failure; Reagent Kits, Diagnostic; Renal Insufficiency; Saponins; Sensitivity and Specificity

We have evaluated the new Roche digoxin "On Line" procedure for use in a pediatric population with particular interest in the potential for interference by digoxin-like immunoreactive factor (DLIF). An initial study comparing digoxin values obtained with the new Roche procedure with determinations on an Abbott TDx, American Dade Stratus, and COBAS-FARA using Microgenics Cedia reagents, found good correlations with these established methods. The Roche method was suitably precise and utilized either serum or plasma. Interference by DLIF was assessed by analyzing specimens from patients not receiving digoxin but likely to contain DLIF, with the argument that non-zero values represent cross-reactivity of anti-digoxin antibodies with DLIF endogenous to these specimens. When specimens from neonates, women with second/third trimester pregnancies, and patients with renal and liver failure were assayed with the Roche, Stratus, and TDx methods, all three methods measured DLIF in some specimens, but the Roche method possessed the lowest overall DLIF interference. The modest extent of DLIF interference and the requirement of a small amount of specimen make the Roche method superior in monitoring digoxin in a pediatric population.

Topics: Digoxin; Drug Monitoring; Humans; Immunoassay; Infant, Newborn; Kinetics; Liver Failure; Renal Insufficiency

To establish a method for the determination of free digoxin in serum for clinical use and to study the relationship between the free and total digoxin concentrations in chronic cardiac insufficiency patients receiving digoxin with different renal function.. The ultrafiltration with fluorescence polarization immunoassay was used to determine the concentration of free digoxin.. The concentrations of digoxin standards in serum were 0.96, 1.92, and 3.84 nmol.L-1. The relative standard deviation was < 7% for intra-day and < 6% for inter-day determinations. The average recovery was 99.95 +/- 2.18%. The ratio of free/total digoxin in chronic cardiac insufficiency patients with renal dysfunction was lower than that in patients with normal kidneys (63.5 +/- 4.7% vs 75.1 +/- 3.9%, P < 0.01).. The present method is simple and reliable. In these patients there is an over-measurement for total digoxin concentration, suggesting the presence of elevated endogenous digoxin-like immunoreactive substances.

Topics: Aged; Aged, 80 and over; Coronary Disease; Digoxin; Heart Failure; Humans; Male; Middle Aged; Renal Insufficiency

We report the first clinical application of a noncompetitive immunometric assay system that provides advantages for the rapid and robust assay of small molecules similar to those realized for larger molecules with two-site immunometric assays. This anti-immune complex assay is based on the interaction of a receptor such as a primary antibody with its ligand, such that new binding sites, recognizable by a secondary antibody, are formed. In this report the system is applied to the measurement of digoxin in serum. Utilizing an anti-complex antibody that recognizes a digoxin-bound primary antibody with affinity > 2000-fold over its binding to the primary antibody alone, we show that this anti-complex assay system provides a high-performance assay for serum samples, being conveniently simple (immobilized primary antibody binds digoxin and then labeled secondary antibody so that when excess unbound label is washed away the immunometric readout reflects the digoxin concentration), rapid (incubation time 1-10 min), sensitive (detection limit 30 ng/L), precise (3-4% within-run CV, 1-8% total CV), and free from interference from digoxin-like immunoreactive factors.

Topics: Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibody Specificity; Antigen-Antibody Complex; Binding, Competitive; Digoxin; Female; Humans; Immunoassay; Molecular Weight; Pregnancy; Quality Control; Renal Insufficiency; Sensitivity and Specificity; Time Factors

Topics: Adult; Aged; Blood Proteins; Cardenolides; Digoxin; Female; Humans; Male; Middle Aged; Reference Values; Renal Insufficiency; Saponins

Topics: Aged; Aged, 80 and over; Digoxin; Drug Interactions; Female; Humans; Renal Insufficiency

We describe a case of digoxin intoxication due to an unadjusted loading dose in a patient with renal failure. The importance of individual calculation of the digoxin dosing regimen in patients with renal failure is reemphasized. The volume of distribution of digoxin decreases significantly in chronic renal failure, due to decreased tissue binding in the uremic state. Accordingly, not only the digoxin maintenance dose, but the digoxin loading dose as well must be adjusted in this condition.

Topics: Aged; Digoxin; Female; Humans; Renal Insufficiency

Three cases are described in which renal failure was accompanied by a lowered apparent volume of distribution of digoxin. In two cases this resulted in frank digoxin toxicity and in one equivocal toxicity. In all three cases digoxin plasma levels were greater than 2 ng/ml. The possible causes of the abnormal distribution of digoxin in renal failure are discussed. Recommendations are outlined for the use of digoxin in patients with renal failure aimed at circumventing the problem raised by a lowered apparent volume of distribution of the drug.

Topics: Cardiotonic Agents; Digoxin; Female; Humans; Male; Middle Aged; Renal Insufficiency; Sodium-Potassium-Exchanging ATPase

Topics: Acute Kidney Injury; Anuria; Chlorothiazide; Diabetes Mellitus; Digoxin; Geriatrics; Gout; Hydrochlorothiazide; Hypertension; Hypertension, Renal; Kidney; Renal Insufficiency; Toxicology

Topics: Acute Kidney Injury; Biomedical Research; Blood Chemical Analysis; Chromatography; Digoxin; Drug Therapy; Feces; Heart Failure; Histocytochemistry; Humans; Peritoneal Dialysis; Renal Insufficiency; Toxicology; Tritium; Urine