Can digoxin (digitalis) cause Acute Kidney Injury (AKI)?

From the Guidelines

Yes, digoxin can cause Acute Kidney Injury (AKI), particularly in patients with pre-existing kidney disease, the elderly, and those on multiple medications. Digoxin-induced AKI typically occurs through indirect mechanisms rather than direct nephrotoxicity, involving digoxin toxicity leading to cardiac dysfunction, which subsequently reduces renal perfusion 1. When digoxin levels become elevated, it can cause arrhythmias, bradycardia, and decreased cardiac output, all of which can compromise blood flow to the kidneys.

Key Considerations

• Digoxin has a narrow therapeutic window and is primarily eliminated by the kidneys, creating a potentially dangerous cycle where initial kidney dysfunction leads to drug accumulation, which further worsens kidney function.
• Regular monitoring of digoxin levels, kidney function, and electrolytes (especially potassium, as hypokalemia increases digoxin toxicity) is essential for patients on this medication.
• Early signs of digoxin toxicity include nausea, vomiting, visual disturbances, and confusion, which may precede kidney injury.

Patient Risk Factors

• Pre-existing kidney disease
• Elderly patients
• Patients on multiple medications, particularly diuretics, ACE inhibitors, or certain antibiotics like clarithromycin

Recommendations

• Temporary discontinuation of digoxin is recommended in people with a GFR < 60 ml/min/1.73 m2 who have serious intercurrent illness that increases the risk of AKI 1.
• Close monitoring of digoxin levels and kidney function is crucial to prevent AKI in patients taking digoxin.

From the FDA Drug Label

Digoxin is primarily excreted by the kidneys; therefore, patients with impaired renal function require smaller than usual maintenance doses of digoxin Laboratory Test Monitoring Patients receiving digoxin should have their serum electrolytes and renal function (serum creatinine concentrations) assessed periodically; Furthermore, caution should be exercised when combining digoxin with any drug that may cause a significant deterioration in renal function, since a decline in glomerular filtration or tubular secretion may impair the excretion of digoxin

Digoxin and Acute Kidney Injury (AKI):

• The FDA drug label does not directly state that digoxin can cause AKI.
• However, it does mention that digoxin is primarily excreted by the kidneys and that patients with impaired renal function require smaller doses.
• It also recommends monitoring renal function in patients receiving digoxin.
• Caution is advised when using digoxin in patients with renal impairment or when combining it with drugs that may worsen renal function, as this may increase the risk of toxicity 2.
• The label does not provide direct evidence of digoxin causing AKI, but it highlights the importance of careful dose selection and monitoring in patients with renal impairment 2.

From the Research

Digoxin and Acute Kidney Injury (AKI)

• Digoxin toxicity can be life-threatening, and its management is challenging, especially in patients with acute kidney injury (AKI) 3.
• The use of digoxin-specific antibody fragments is recommended in severe digoxin toxicity, but their clearance is prolonged in severe renal impairment, leading to rebound toxicity 3.
• Plasma exchange (PEX) has been used to remove digoxin-DSA complexes in patients with severe digoxin toxicity and AKI, bypassing renal excretion 3.

Risk of Elevated Digoxin Concentrations

• The optimal loading dose of digoxin in patients with reduced kidney function is unknown, and tertiary references recommend reduced loading doses 4.
• A retrospective analysis found that the frequency of supratherapeutic digoxin concentrations was similar between patients with AKI, chronic kidney disease (CKD), and non-AKI/CKD 4.
• However, another study found that patients with creatinine clearance below 60 mL/min were more likely to experience toxic serum concentrations of digoxin after a loading dose 5.

Digoxin Toxicity and AKI

• Digoxin toxicity can be precipitated by acute renal failure, and physicians should maintain a high index of suspicion and be comfortable with administering digoxin-specific antibody fragments in these scenarios 6.
• A case report highlighted the challenges in managing severe digoxin toxicity in patients with concurrent AKI, and the use of PEX enabled digoxin-DSA complex removal 3.

Drug-Induced Acute Kidney Injury

• Drug-induced acute kidney injury (DI-AKI) is a significant cause of AKI, and digoxin is one of the nephrotoxic medications that can cause DI-AKI 7.
• A cohort study found that DI-AKI showed lower severity and mortality compared to other AKI etiologies, but had a similar need for acute kidney support therapy (AKST) 7.