digoxin and Acute-Kidney-Injury

The high rates of drug-induced acute renal failure, worsening chronic renal dysfunction and systemic toxicity of renally excreted drugs in the elderly can be minimised by carefully assessing renal function, avoiding potentially nephrotoxic drugs as much as possible and closely monitoring drug concentrations and renal function when they must be used. The co-existence of impaired renal function, degenerative vascular disease or cardiac failure in the elderly substantially increases the risk of renal toxicity. When in doubt about potential nephrotoxicity or an increased risk of systemic toxicity from renally excreted drugs in the elderly, the practitioner should consult the numerous published guidelines.

Topics: Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Aminoglycosides; Angiotensin-Converting Enzyme Inhibitors; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents; Chronic Disease; Contrast Media; Digoxin; Diuretics; Humans; Kidney; Kidney Diseases; Kidney Function Tests; Middle Aged; Risk Factors

Topics: Acute Kidney Injury; Airway Obstruction; Anemia, Hemolytic; Arteriovenous Fistula; Asphyxia Neonatorum; Cardiac Output; Digoxin; Ductus Arteriosus, Patent; Female; Heart Failure; Humans; Hyperthyroidism; Hypoglycemia; Infant; Infant, Newborn; Isoproterenol; Medical History Taking; Pregnancy; Pulmonary Edema; Pulmonary Valve; Sepsis; Streptococcal Infections; Tachycardia, Paroxysmal; Tricuspid Valve Insufficiency

Topics: Abortion, Septic; Acute Kidney Injury; Analgesics; Angiotensin II; Animals; Anti-Bacterial Agents; Antihypertensive Agents; Catecholamines; Digoxin; Disseminated Intravascular Coagulation; Diuretics; Dogs; Female; Hemodynamics; Humans; Hypnotics and Sedatives; Hypotension; Kidney; Kidney Concentrating Ability; Kidney Cortex Necrosis; Pregnancy; Pregnancy Complications, Infectious; Prostaglandins; Rabbits; Renal Dialysis; Renin; Sepsis; Shock, Septic; Sympathetic Nervous System; Tranquilizing Agents; Water-Electrolyte Balance

Topics: Acute Kidney Injury; Administration, Oral; Arrhythmias, Cardiac; Digitoxin; Digoxin; Drug Interactions; Electric Countershock; Half-Life; Humans; Injections, Intramuscular; Injections, Intravenous; Liver Diseases; Malabsorption Syndromes; Pharmaceutical Vehicles; Phenytoin; Potassium; Thyroid Diseases

Acute renal failure (ARF) is a clinical critical syndrome with rapid and severe decline of renal function. Complications of ARF, especially its cardiac complications (cardiorenal syndrome type 3, CRS-3), are the main causes of death in patients with ARF. However, the shortage and limited efficacy of therapeutic drugs make it significant to establish new large-scale drug screening models. Based on the Nitroreductase/Metronidazole (NTR/MTZ) cell ablation system, we constructed a

Topics: Acute Kidney Injury; Animals; Animals, Genetically Modified; Cardio-Renal Syndrome; Cardiovascular Diseases; Digoxin; Disease Models, Animal; Drug Evaluation, Preclinical; Enalapril; Epithelial Cells; Humans; Kidney Tubules; Larva; Metronidazole; Regional Blood Flow; Thioctic Acid; Treatment Outcome; Zebrafish

Digoxin is commonly prescribed for heart failure and atrial fibrillation, but there is limited data on its safety in patients with chronic kidney disease (CKD). We conducted a population-based cohort study using the pre-end stage renal disease (ESRD) care program registry and the National Health Insurance Research Database in Taiwan. Of advanced CKD patient cohort (N = 31,933), we identified the digoxin user group (N = 400) matched with age and sex non-user group (N = 2,220). Multivariable Cox proportional hazards and sub-distribution hazards models were used to evaluate the association between digoxin use and the risk of death, cardiovascular events (acute coronary syndrome, ischemic stroke, or hemorrhagic stroke) and renal outcomes (ESRD, rapid decline in estimated glomerular filtration rate-eGFR, or acute kidney injury). Results showed that all-cause mortality was higher in the digoxin user group than in the non-user group, after adjusting for covariates (adjusted hazard ratio, aHR 1.63; 95% CI 1.23-2.17). The risk for acute coronary syndrome (sub-distribution hazard ratio, sHR 1.18; 95% CI 0.75-1.86), ischemic stroke (sHR 1.42; 95% CI 0.85-2.37), and rapid eGFR decline (sHR 1.00 95% CI 0.78-1.27) was not significantly different between two groups. In conclusion, our study demonstrated that digoxin use was associated with increased mortality, but not cardiovascular events or renal function decline in advanced CKD patients. This finding warns the safety of prescribing digoxin in this population. Future prospective studies are needed to overcome the limitations of cohort study design.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases; Digoxin; Female; Humans; Male; Middle Aged; Renal Insufficiency, Chronic; Taiwan

Topics: Acute Kidney Injury; Aged, 80 and over; Amoxicillin; Anti-Arrhythmia Agents; Anti-Bacterial Agents; Atrial Fibrillation; Bradycardia; Bundle-Branch Block; Clarithromycin; Digoxin; Drug Interactions; Electrocardiography; Female; Helicobacter Infections; Helicobacter pylori; Humans; Hyperkalemia; Immunoglobulin Fab Fragments; Omeprazole; Tachycardia, Ventricular

Topics: Acute Kidney Injury; Aged, 80 and over; Anti-Arrhythmia Agents; Atrial Fibrillation; Digoxin; Electrocardiography; Female; Humans

Topics: Acute Kidney Injury; Aged, 80 and over; Atrial Fibrillation; Confusion; Delirium; Diagnosis, Differential; Digoxin; Electrocardiography; Female; Heart Failure; Humans; Immunoglobulin Fab Fragments; Lung Diseases; Medically Uninsured; Nausea; Poisoning; Radiography, Thoracic; Vomiting

Topics: Acute Kidney Injury; Aged; Agglutinins; Anti-Arrhythmia Agents; Atrial Fibrillation; Bradycardia; Digoxin; Dosage Forms; Dose-Response Relationship, Drug; Drug-Related Side Effects and Adverse Reactions; Electrocardiography; Fatigue; Humans; Male; Treatment Outcome; Vision Disorders; Vomiting

Dose adjustment for certain drugs is required in patients with reduced renal function to avoid toxicity as many drugs are eliminated by the kidneys. The aim of this study was to assess whether appropriate dosage adjustments were made in hospitalized patients with renal impairment.. A prospective cross-sectional study was carried out in the internal medicine wards of Tikur Anbessa Specialized Hospital. All patients with creatinine clearance ≤ 59 ml/min admitted to hospital between April and July, 2013 were included in the analysis. Data regarding serum creatinine level, age, sex and prescribed drugs and their dosage was collected from the patients' medical records. Serum creatinine level ≥ 1.2 mg/dL was used as a cutoff point in pre-selection of patients. The estimated creatinine clearance was calculated using the Cockcroft- Gault (CG) equation. Guideline for Drug prescribing in renal failure provided by the American College of Physicians was used as the standard for dose adjustment.. Nine percent (73/810) of medical admissions were found to have renal impairment (CrCl  ≤ 59 ml/min). There were 372 prescription entries for 73 patients with renal impairment. Dose adjustment was required in 31 % (115/372) of prescription entries and fifty eight (51 %) prescription entries requiring dose adjustment were found to be inappropriate. Of 73 patients, 54 patient received ≥ 1 drug that required dose adjustment (median 2; range 1-6). Fifteen (28 %) patients had all of their drugs appropriately adjusted while twenty two (41 %) patients had some drugs appropriately adjusted, and seventeen (31 %) of patients had no drugs appropriately adjusted. No patients were documented to have received dialysis.. The findings indicate that dosing errors were common among hospitalized patients with renal impairment. Improving the quality of drug prescription in patients with renal impairment could be of importance for improving the quality of care.

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Aged, 80 and over; Allopurinol; Anti-Arrhythmia Agents; Anti-Bacterial Agents; Anti-Ulcer Agents; Antifungal Agents; Antihypertensive Agents; Ceftazidime; Cimetidine; Creatinine; Cross-Sectional Studies; Digoxin; Diuretics; Drug Dosage Calculations; Drug Prescriptions; Enalapril; Ethiopia; Female; Fluconazole; Gout Suppressants; Hospitalization; Humans; Male; Medication Errors; Middle Aged; Pharmaceutical Preparations; Prospective Studies; Renal Insufficiency, Chronic; Severity of Illness Index; Spironolactone; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin; Young Adult

Topics: Acute Kidney Injury; Cardiomyopathy, Dilated; Cardiotonic Agents; Colectomy; Critical Care; Digoxin; Drug Interactions; Female; Humans; Laparotomy; Middle Aged; Norepinephrine; Shock, Septic; Vasoconstrictor Agents

The management of digoxin therapy using pharmacokinetics in a patient undergoing continuous venovenous hemofiltration (CVVH) is reported.. A 46-year-old African-American woman with New York Heart Association class IV, American College of Cardiology- American Heart Association stage D heart failure arrived from an outside facility with complaints of dyspnea after minimal exertion, orthopnea, and lower-extremity edema. A transthoracic echocardiogram revealed an estimated left ventricular ejection fraction of 15%. The patient subsequently required left ventricular assist device placement on hospital day 5 as a potential bridge to transplantation. A total digoxin loading dose of 500 μg i.v. (8.2 μg/kg) was given in two divided doses six hours apart. The next morning, the serum digoxin concentration was 1.9 ng/mL, and the patient was started on a maintenance digoxin dosage of 125 μg i.v. daily. On postoperative day (POD) 20, the patient developed acute kidney injury, and CVVH was initiated. The sieving coefficient (Sc), transmembrane clearance (CLtm), digoxin concentration in ultrafiltration fluid (Cuf), and need for supplemental digoxin were determined to account for CVVH- associated digoxin loss. After 14 days of CVVH, the patient's clinical condition improved, and CVVH was transitioned to intermittent hemodialysis. On POD 66, the patient was discharged to an extended-care facility without adverse reactions related to digoxin therapy.. Analysis of serum digoxin concentration and digoxin Cuf values suggested that digoxin was cleared by CVVH, allowed calculation of Sc and CLtm values, and facilitated determination of digoxin requirements in a critically ill patient requiring CVVH.

Topics: Acute Kidney Injury; Cardiotonic Agents; Critical Illness; Digoxin; Dose-Response Relationship, Drug; Echocardiography; Female; Heart Failure; Heart-Assist Devices; Hemofiltration; Humans; Middle Aged

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Bradycardia; Cardiotonic Agents; Digoxin; Female; Humans; Takotsubo Cardiomyopathy

Topics: Acute Kidney Injury; Antidotes; Bromazepam; Digoxin; Female; Fluid Therapy; Humans; Hydroxyethyl Starch Derivatives; Hyperkalemia; Immunization, Passive; Immunoglobulin Fab Fragments; Middle Aged; Poisoning; Polygeline; Suicide, Attempted; Time Factors; Ventricular Premature Complexes

Topics: Acute Kidney Injury; Aged; Ankle Injuries; Anti-Arrhythmia Agents; Antidotes; Digoxin; Female; Fractures, Bone; Humans; Immunoglobulin Fab Fragments; Respiratory Tract Infections; Syncope

Topics: Acute Disease; Acute Kidney Injury; Aged; Antibodies; Digitalis; Digoxin; Humans; Immunoglobulin Fab Fragments; Immunoglobulin Fragments; Plasmapheresis

Topics: Acute Kidney Injury; Aged; Atrial Fibrillation; Bundle-Branch Block; Digitalis; Digoxin; Electrocardiography; Humans; Male; Metoprolol; Tachycardia, Ventricular

Topics: Acute Kidney Injury; Aged; Cardiotonic Agents; Chronic Disease; Digoxin; Emergency Medicine; Fatal Outcome; Female; Heart Failure; Humans; Hyperkalemia; Immunoglobulin Fab Fragments; Natriuretic Peptide, Brain

The aim of this study was to clarify the effects of renal failure on intestinal secretion of quinolone antibacterial drugs.. Pharmacokinetics of grepafloxacin, levofloxacin, and ciprofloxacin in cisplatin-induced acute renal failure (ARF) rats were evaluated, and intestinal and biliary clearance studies were examined. Transport experiments using culture cells were performed.. The bioavailability of grepafloxacin in ARF rats was 1.2-fold higher than that in normal rats. On the other hand, the bioavailability of ciprofloxacin in ARF rats was markedly decreased to half of that in normal rats, and that of levofloxacin was not changed. Intestinal clearance of grepafloxacin in ARF rats was 75% of that in normal rats, whereas that of ciprofloxacin was 1.4-fold higher than in normal rats, and that of levofloxacin was comparable between normal and ARF rats. Transport experiments using P-glycoprotein-expressing LLC-GA5-COL150 cells and human intestinal Caco-2 cells suggested that grepafloxacin and levofloxacin were substrates of P-glycoprotein and that ciprofloxacin was not, and that intestinal secretion of ciprofloxacin was mediated by a specific transport system distinct from organic cation and anion transporters and multidrug resistance-associated protein 2.. Cisplatin-induced ARF differentially modulated the bioavailability and intestinal secretion of quinolones in rats.

Topics: Acute Kidney Injury; Animals; Anti-Infective Agents; Antineoplastic Agents; Bile Ducts; Biological Availability; Blotting, Western; Caco-2 Cells; Ciprofloxacin; Cisplatin; Duodenum; Fluoroquinolones; Humans; Injections, Intravenous; Levofloxacin; Male; Ofloxacin; Piperazines; Rats; Rats, Wistar; Time Factors

Digoxin-specific antibodies (Fab) are currently the treatment of choice for digoxin intoxication. These fragments bind to digoxin, leading to Fab-digoxin complexes, and promote the release of receptor-bound digoxin. These complexes are renally excreted. In the case of anuria, they could be dissociated and lead to renewed intoxication. In this case plasma exchanges are proposed. We report the case of an anuric patient with digoxin intoxication, treated with a Fab injection, followed by a plasma exchange 16 hours later, a second Fab injection was given followed by two plasma exchanges, 38 and 86 hours later. The disappearance of cardiac abnormalities showed the efficiency of the Fab, the drop in serum digoxin concentration and the high digoxin concentration in the exchanged plasma indicate effective elimination. The association of Fab and plasma exchanges could be proposed in the case of digoxin intoxication in the anuric patient.

Topics: Acute Kidney Injury; Aged; Anti-Arrhythmia Agents; Anuria; Digoxin; Humans; Immunoglobulin Fab Fragments; Male; Plasma Exchange

Topics: Acute Kidney Injury; Aged; Aged, 80 and over; Atrial Fibrillation; Cardiotonic Agents; Digoxin; Electrocardiography; Fatal Outcome; Female; Humans; Immunoglobulin Fab Fragments

Life-threatening digoxin toxicity may be effectively treated with digoxin-specific antibody fragments (Fab). However, in end-stage renal disease, the digoxin-Fab complexes persist in the circulation and dissociate, potentially resulting in rebounding free digoxin levels and the recurrence of symptomatic toxicity. To prevent this rebound phenomenon, plasma exchange (PE) has been implemented for the removal of the digoxin-Fab complexes in renal failure. However, there is only one case report describing its use in this setting. To better determine the optimal timing of PE after Fab administration, we performed two PE treatments (each preceded by Fab) in a patient with acute renal failure and acute digoxin poisoning. The admission serum digoxin level was 21 ng/mL. The timing of the PE treatments relative to Fab dosing was as follows: the first PE was performed 26 hours post-Fab, and the second PE was performed 2.5 hours post-Fab. The plasma ultrafiltrate digoxin concentration was 2.5-fold greater when PE was performed 2.5 hours versus 26 hours after Fab administration (19.9 versus 8.1 ng/mL). The combined total amount of digoxin removed in the ultrafiltrate plasma was minimal (0.13 mg), less than 1% of the total amount of ingested drug. We conclude that the optimal timing of PE is within the first 3 hours after Fab administration. Although PE is efficacious for removing digoxin-Fab complexes, thus preventing rebound digoxin toxicity, it is not efficacious for improving total digoxin clearance because of the large apparent volume of distribution of digoxin (5 to 8 L/kg).

Topics: Acute Kidney Injury; Digoxin; Humans; Immunoglobulin Fab Fragments; Male; Middle Aged; Plasma Exchange; Poisoning; Suicide, Attempted

The 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors lovastatin and simvastatin have been associated with rhabdomyolysis in cardiac transplant recipients. Herein, we report a case of a 52-year-old male recipient of a cardiac transplant who developed rhabdomyolysis and acute renal failure caused by simvastatin precipitated by multiple drug interactions.. The patient had a history of cardiac transplantation (5 years before) and presented with a 2-day history of dark urine preceded by 2 weeks of diffuse myalgias. He had been maintained on cyclosporine throughout the entire post-transplant period. Simvastatin was added and pravastatin was discontinued 2 months before admission. Two weeks before the onset of muscle symptoms, digoxin and verapamil were started for new-onset atrial fibrillation. Creatinine phosphokinase levels peaked at 950,000 IU with serum creatinine of 3.3 mg/dL (baseline, 1.8 mg/dL).. Review of the medication history indicates a temporal association between the addition of 3 drugs (simvastatin, verapamil, and digoxin) to the medication regimen already containing cyclosporine and the episode of rhabdomyolysis. All of these drugs are cytochrome P450 3A4 and/or P-glycoprotein substrates that are known from previous pharmacokinetic studies to individually produce substantial increases in levels of simvastatin.. We believe this case illustrates that avoiding the use of drugs that are cytochrome P450 3A4 and/or P-glycoprotein substrates reduces the risk of rhabdomyolysis caused by 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors.

Topics: Acute Kidney Injury; Anti-Arrhythmia Agents; Cyclosporine; Digoxin; Drug Interactions; Enzyme Inhibitors; Heart Transplantation; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunosuppressive Agents; Male; Middle Aged; Rhabdomyolysis; Simvastatin; Verapamil

Cardiac involvement rarely occurs in classic hemolytic uremic syndrome (HUS); it is often fatal.. The first patient, a 21-month-old boy, developed classic HUS with acute renal failure. Peritoneal dialysis was performed for 20 days. On the 10th day of dialysis, myocardial infarction occurred, probably related to coronary thrombus. The patient was given heparin and antibiotics because of an unexplained fever. The outcome was favorable despite antero-apical cardiac necrosis, and moderated chronic renal failure. The second patient, a 24-month-old girl, also showed a classic HUS, which required peritoneal dialysis for 10 days. Dilated cardiomyopathy with cardiac failure appeared on the 4th day of dialysis, not related to the volume overload and metabolic consequences of the acute renal failure, such as systemic hypertension or ineffective dialysis. On the 5th day of dialysis neurological involvement appeared. Neurological, cardiac and renal outcome was favorable. The third patient, a 25-month-old girl, developed a classical HUS, requiring peritoneal dialysis for 25 days. No cardiac insult appeared during the acute phase of the disease. After dialysis, the child had chronic renal failure (creatinine clearance: 15 mL/min/1.73 m2). Dilated cardiomyopathy appeared 3 months later, without definite etiology. The outcome was favorable with digoxin treatment.. A cardiac involvement should also be searched for in the acute phase of HUS and several months later.

Topics: Acute Kidney Injury; Cardiac Output, Low; Cardiomyopathy, Dilated; Cardiotonic Agents; Creatinine; Digoxin; Female; Follow-Up Studies; Hemolytic-Uremic Syndrome; Humans; Infant; Kidney Failure, Chronic; Male; Myocardial Infarction; Peritoneal Dialysis; Psychomotor Agitation; Sleep Stages; Treatment Outcome

Topics: Acute Kidney Injury; Calcium Chloride; Cardiotonic Agents; Digoxin; Humans; Hyperkalemia

Topics: Acute Disease; Acute Kidney Injury; Cardiotonic Agents; Chronic Disease; Digoxin; Humans; Hyperkalemia

Topics: Acute Kidney Injury; Calcium Chloride; Cardiotonic Agents; Digoxin; Humans; Hyperkalemia

Review of the literature suggests that misdiagnosis of terminal illness is infrequent. In the first 6 months of the recently established Edmonton Regional Palliative Care Program, two of 330 referrals proved to be in the category of erroneous diagnosis of terminal disease. These two cases are reported, along with discussion of aspects of the time-honored usefulness of careful history and physical examination. This experience highlights the importance of assessment, investigation, and aggressive therapy, even in "terminal" patients, including those in the geriatric population.

Topics: Acute Kidney Injury; Adaptation, Psychological; Aged; Aged, 80 and over; Analgesics, Opioid; Anti-Inflammatory Agents, Non-Steroidal; Antidepressive Agents, Tricyclic; Chest Pain; Coronary Disease; Depression; Diagnosis, Differential; Diagnostic Errors; Digoxin; Female; Geriatrics; Grief; Humans; Morphine; Neoplasms; Nortriptyline; Palliative Care; Stomach Ulcer; Terminally Ill; Weight Loss

Digitalis intoxication is a common problem, mainly because of the narrow margin of safety of digoxin. These patients may have concomitant renal failure. In patients who have renal failure and who have been treated with digoxin-Fab, the elimination of the digoxin-Fab complex is significantly delayed, and there is a risk of dissociation of the complex with rebound of free digoxin and recurrence of toxicity. The high molecular weight of digoxin and digoxin-Fab complex prevents its elimination by hemodialysis or continuous arteriovenous hemofiltration. A 3-day-old newborn with digoxin overdose and acute renal failure was treated with digoxin immune Fab and peritoneal dialysis. Low levels of total digoxin were measured in the dialyzate, indicating poor elimination of the digoxin-Fab complex through peritoneal dialysis.

Topics: Acute Kidney Injury; Adult; Child; Digoxin; Drug Overdose; Female; Humans; Immunoglobulin Fab Fragments; Infant, Newborn; Peritoneal Dialysis; Pregnancy

Topics: Acute Kidney Injury; Aged; Anuria; Digoxin; Female; Humans; Immunoglobulin Fab Fragments

Topics: Acute Kidney Injury; Anti-Bacterial Agents; beta 2-Microglobulin; Creatinine; Digoxin; Hemofiltration; Humans; Metabolic Clearance Rate; Molecular Weight; Phosphates; Renal Dialysis; Urea; Uric Acid

A patient with renal failure due to myeloma kidney and coincident digitalis intoxication due to prescribed daily digoxin administration was treated with digoxin-specific antibody fragments and plasmapheresis. Rapid response to therapy was noted, removal of digoxin-antidigoxin antibody complexes was confirmed, and prevention of delayed rebound toxicity was documented. We suggest that this is the therapy of choice in similar individuals.

Topics: Acute Kidney Injury; Aged; Digoxin; Female; Humans; Immunoglobulin Fab Fragments; Multiple Myeloma; Plasmapheresis; Poisoning; Renal Dialysis

Severe digitalis intoxication today is preferentially treated by intravenous infusion of Fab fragments of digoxin antibodies (Digitalis Antidot BM). The kinetics of Fab fragments in the circulation are well known when kidney function is normal or slightly impaired. There are no data available, however, in complete renal failure. We observed a patient with life-threatening digitalis intoxication (serum digoxin, 3.7 ng/ml) and anuria, who was treated successfully by 160 mg Fab fragments i.v. Serum digoxin and Fab fragment concentrations could be followed for 229 h. The extrarenal clearance of Fab fragments was lower (5.6 ml/min) than in patients with normal kidney function (10.9 ml/min). This finding suggests that lower doses than usual might be sufficient for treating patients with severe digitalis intoxication and renal failure.

Topics: Acute Kidney Injury; Digoxin; Humans; Immunoglobulin Fab Fragments; Infusions, Intravenous; Male; Metabolic Clearance Rate; Middle Aged; Ventricular Fibrillation

A case of systemic allergic-type vasculitis after the administration of quinidine and digoxin is described. The renal biopsy findings are unique in that they describe an arteritis with eosinophilic infiltration and non-caseating granulomata. We believe quinidine is the antigen that was responsible for the reported findings.

Topics: Acute Kidney Injury; Digoxin; Drug Therapy, Combination; Eosinophilia; Granuloma; Humans; Male; Middle Aged; Quinidine; Vasculitis, Leukocytoclastic, Cutaneous

A 41-year-old man with combined renal and hepatic dysfunction was noted to have marked elevations in serum digoxin concentration subsequent to the discontinuation of digoxin therapy. These elevations (peak value 8.6 ng/ml), as measured by both radioimmunoassay and fluorescence polarization immunoassay, were not associated with electrocardiographic evidence of digitalis toxicity. Using a combined high-performance liquid chromatography/radioimmunoassay, accumulation and immunoassay cross-reactivity of conjugates of digoxigenin monodigitoxoside (cardioinactive metabolites of digoxin) were found to be the basis of the observed false elevation in digoxin concentration.

Topics: Acute Kidney Injury; Adult; Cerebral Hemorrhage; Chromatography, High Pressure Liquid; Cross Reactions; Diabetes Mellitus, Type 1; Digoxin; False Positive Reactions; Fluorescent Antibody Technique; Humans; Hypertension; Immunoassay; Liver Diseases; Male; Radioimmunoassay; Renal Dialysis

A digitalized 75-year-old patient with postoperative renal failure demonstrated a progressive rise in serum digoxin concentration, peaking at 3.4 nmol X L-1 three days following discontinuance of the drug. This was accompanied by cardiac bradyarrhythmias. Although the serum digoxin concentration had already started to climb from a therapeutic level prior to the discontinuance of the drug, the unabated and substantial rise was consistent with a dramatic decrease in the apparent volume of distribution of digoxin accompanying acute renal failure. Serum digoxin levels were determined with fluorescence polarization immunoassay, which has an improved specificity when compared to the commonly used radioimmunoassays for digoxin.

Topics: Acute Kidney Injury; Aged; Arrhythmias, Cardiac; Digoxin; Female; Humans; Kinetics; Postoperative Complications

Digitalis-like factors were assayed by radioimmunoassay of digoxin in 6 bile samples obtained from patients at autopsy and in plasma from three patients with combined hepatic and acute renal failure. None of the patients received digoxin. Digitalis like factor values in bile samples were 23 to 85 nmol digoxin equivalents/1. Bile salt concentrations ranged from 38-104 mmol/l in the bile and 28-184 mumol/l in the plasma of these subjects. Bile, plasma digitalis like factor extracts and bile salt standards (0.1-3 mM) showed concentration dependent displacement of [125I]-digoxin from digoxin antibody, inhibition of hog brain Na,K-ATPase and displacement of [3H]-ouabain from Na,K-ATPase. The concentration-displacement curves suggest that bile salts could account for 50-79% of the total digitalis like factors in the six bile samples and 2-7% in the plasma of the three patients. High performance liquid chromatographic fractionation of a bile sample showed digitalis like factor peaks co-eluating with standards of tauro- and glycocholate, tauro- and glycochenodeoxycholate and tauro- and glycodeoxycholate. These bile salt peaks accounted for 78% of the total digitalis like factors in all high performance liquid chromatographic peaks in bile, but only 7% of the total digitalis like factor activity in all high performance liquid chromatographic peaks in an extract of plasma from one of the patients with hepatic and renal failure. The bile salts appear to be examples of endogenous digitalis like compounds which do not act by simple competitive ligand binding to antidigoxin antibody and Na,K-ATPase. They make an important contribution to digitalis like factor activity in bile, but not in plasma.

Topics: Acute Kidney Injury; Adult; Antibodies; Bile; Bile Acids and Salts; Blood Proteins; Cardenolides; Chromatography, High Pressure Liquid; Digoxin; Female; Humans; Liver Diseases; Male; Middle Aged; Ouabain; Radioimmunoassay; Saponins; Sodium-Potassium-Exchanging ATPase

Topics: Acute Kidney Injury; Adolescent; Adult; Digoxin; False Positive Reactions; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Renal Dialysis

Topics: Acute Kidney Injury; Blood Proteins; Cardenolides; Digoxin; Humans; Liver Diseases; Radioimmunoassay; Saponins

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Digoxin; Fluorescence Polarization; Humans; Immunoassay; Kidney Failure, Chronic; Middle Aged

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.

Topics: Acute Kidney Injury; Aged; Chromatography, High Pressure Liquid; Digoxin; Dose-Response Relationship, Drug; Heart Failure; Humans; Injections, Intravenous; Male; Reagent Kits, Diagnostic; Time Factors

This study was performed to get more informations on the renal and extracorporeal elimination of digoxin. The first part of this study demonstrated that a radioimmunoassay for digoxin or a specific tritium label of digoxin is necessary to measure renal digoxin clearances. Randomly labeled 3H-digoxin may loose its label and thus give incoherent results. A comparison of digoxin and inulin clearances in patients demonstrates glomerular filtration as the major renal excretion pathway of digoxin, but a major fraction of the glycoside is excreted by tubular secretion. Opposite to digoxin, beta-methyl-digoxin undergoes less tubular secretion but eventually additional tubular reabsorption. The insertion of digoxin and quinidine may be a further prove for the existence of a tubular secretion of digoxin. While the renal clearance of digoxin is significantly bigger than the renal clearance of creatinine, additional quinidine therapy reduces the renal clearance of digoxin to the one of creatinine. We studied the renal excretion mechanism of digoxin additionally in an animal model of acute prerenal failure. After a 33% reduction of renal arterial pressure glomerular filtrate dropped 68%. Under these circumstances the renal excretion mechanism of digoxin measured as the digoxin to inulin clearance ratio did not change. We evaluated the efficiency of hemodialysis, hemofiltration and hemoperfusion to eliminate digoxin. Although digoxin is eliminated by all three methods, even the most effective, hemoperfusion, can reduce total body content of digoxin less than 3%. Thus we conclude that all these methods have no indication in the treatment of digoxin intoxications.

Topics: Acetyldigoxins; Acute Kidney Injury; Animals; Digoxin; Dogs; Humans; Inulin; Medigoxin; Renal Dialysis

Topics: Acute Kidney Injury; Adult; Aged; Arrhythmias, Cardiac; Diabetes Mellitus; Digoxin; Female; Half-Life; Hemoperfusion; Humans; Hypotension; Kidney Failure, Chronic; Male; Middle Aged; Polystyrenes; Polyvinyls; Renal Dialysis

Topics: Acute Kidney Injury; Cross Reactions; Digoxin; Humans; Immunoassay; Kinetics; Male; Middle Aged; Uremia

Topics: Acute Kidney Injury; Adult; Digoxin; Female; Heart Failure; Humans

Topics: Acute Kidney Injury; Aged; Digoxin; Humans; Liver Diseases; Male

Topics: Acute Kidney Injury; Adrenergic beta-Antagonists; Anti-Inflammatory Agents; Arthritis, Rheumatoid; Coronary Disease; Digoxin; Female; Humans; Hypertension, Renal; Indomethacin; Male; Metoprolol; Middle Aged; Penicillamine

Topics: Acid-Base Imbalance; Acute Kidney Injury; Blood Volume; Cardiac Surgical Procedures; Cardiac Tamponade; Child; Child, Preschool; Digoxin; Humans; Hypokalemia; Infant; Patient Care Team; Postoperative Care; Postoperative Complications

Topics: Acute Kidney Injury; Aged; Colestipol; Digoxin; Female; Humans; Polyamines

The probability of experiencing adverse drug reactions increases with age. Polypharmacy, pharmacokinetic changes (altered drug distribution, reduced renal and hepatic drug clearances), unusual pharmacological effects and impaired compensatory mechanisms are the principal reasons for the diminished tolerance of elderly patients to several drugs. Especially neuroleptics, antidepressants, tranquilizers, digoxin, potent diuretics, betablockers, and antiarrhythmics have to be employed with special care. To prevent adverse reactions in geriatric patients, prescriptions should be limited to a few essential drugs, dosage reduced, and dosing regimens simplified. However, therapeutic nihilism can never be justified by old age alone.

Topics: Acute Kidney Injury; Adrenergic beta-Antagonists; Aged; Antidepressive Agents; Antipsychotic Agents; Arrhythmias, Cardiac; Benzodiazepines; Creatine; Digoxin; Diuretics; Drug-Related Side Effects and Adverse Reactions; Female; Geriatrics; Humans; Hypotension; Male

1 Twenty-two dialysis dependent patients received an intravenous loading dose of digoxin of 10 microgram/kg and the mean +/- s.d. serum digoxin concentration 24 h later was 1.5 ng/ml +/- 0.4 (range 0.8--2.1 ng/ml). No evidence of toxicity was observed. 2 The average apparent volume of distribution of digoxin in dialysis dependent patients was found to be reduced by about one third compared with that reported for individuals with normal renal function, but there was great variation. 3 An appropriate intravenous loading dose of digoxin in most patients with advanced renal failure is 10 microgram/kg.

Topics: Acute Kidney Injury; Adult; Aged; Digoxin; Electrolytes; Half-Life; Humans; Kidney Failure, Chronic; Male; Middle Aged; Time Factors

The pharmacokinetics of digoxin, the most frequently used digitalis preparation, are reviewed. The dominate serum turnover time is about 34 hours, and is not affected by the route of administration. Excretion is largely as unchanged digoxin in the urine and this excretion is compromised in renal failure. Serum levels of digoxin (determined by radioimmunoassay) are generally available and are useful clinically in assessment of both toxicity and the state of underdigitalization, even though significant overlap exists. Special problems are presented in patients with myocardial infarction, pulmonary heart disease, and thyroid disease.

Topics: Acute Kidney Injury; Aging; Digitalis Glycosides; Digoxin; Heart Rate; Kidney; Kinetics; Myocardial Contraction; Myocardial Infarction; Obesity; Pulmonary Heart Disease; Structure-Activity Relationship; Thyroid Diseases; Water-Electrolyte Balance

Plasma digoxin and digitoxin determination has proven to have an important bearing, particularly in patients with renal failure. It permits early detection of digitalis intoxication in the absence of marked clinical and ECG evidence, and adjustment of dosage accordingly. Also, in patent intoxication it makes it possible to select the right moment for resumption of therapy. To illustrate the importance of the method some cases are cited involving plasma digoxin and digitoxin determination.

Topics: Acute Kidney Injury; Bradycardia; Creatinine; Digitalis Glycosides; Digitoxin; Digoxin; Heart Failure; Humans; Kidney Failure, Chronic

Topics: Acute Kidney Injury; Cardiac Glycosides; Digoxin; Evaluation Studies as Topic; Humans

Topics: Acute Kidney Injury; Adult; Aged; Digoxin; Female; Heart Failure; Humans; Male; Middle Aged; Renal Dialysis; Strophanthins; Tritium; Uremia

Topics: Acute Kidney Injury; Aged; Aortic Aneurysm; Atrial Fibrillation; Atrial Flutter; Digoxin; Humans; Male; Middle Aged; Postoperative Complications; Tachycardia

Topics: Acute Kidney Injury; Adolescent; Adult; Aged; Blood Urea Nitrogen; Digoxin; Feces; Female; Heart Failure; Humans; Male; Middle Aged; Nephrectomy; Peritoneal Dialysis; Renal Dialysis; Tritium

Topics: Acute Kidney Injury; Animals; Digitalis; Digoxin; Hypokalemia; Membrane Potentials; Mice; Myocardium; Plants, Medicinal; Plants, Toxic; Potassium Deficiency; Tritium

Topics: Acute Kidney Injury; Adult; Animals; Bile; Chromatography, Paper; Digoxin; Humans; Intestinal Mucosa; Kidney Failure, Chronic; Liver; Middle Aged; Myocardium; Nephrectomy; Organ Size; Tritium; Ureteral Obstruction

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