Ethambutol and Acute Kidney Injury
Ethambutol can cause acute kidney injury (AKI), particularly in patients with pre-existing renal insufficiency, as it is primarily excreted by the kidneys and can accumulate to toxic levels when renal function is impaired. 1, 2
Mechanism of Ethambutol-Related Renal Toxicity
- Ethambutol is primarily eliminated through the kidneys, with approximately 50% of the initial dose excreted unchanged in urine within 24 hours 2
- Marked accumulation of ethambutol occurs in patients with renal insufficiency, which increases the risk of toxicity 2
- The drug's half-life is significantly prolonged in patients with impaired renal function, ranging from 7.4 to 11.8 hours compared to normal kidney function 3
Risk Factors for Ethambutol-Induced AKI
- Pre-existing renal insufficiency significantly increases the risk of ethambutol nephrotoxicity 1
- Higher doses (>30 mg/kg/day) of ethambutol increase the risk of all toxicities, including renal effects 1
- The elimination rate of ethambutol correlates significantly with creatinine clearance, making patients with reduced GFR particularly vulnerable 3
- End-stage renal disease patients on dialysis are at especially high risk due to reduced drug clearance 4, 5
Clinical Presentation and Diagnosis
- AKI is diagnosed by a 50% or greater sustained increase in serum creatinine over a short period of time, reflected as a rapid decrease in eGFR 6
- People with diabetes are at higher risk of AKI than those without diabetes 6
- Ethambutol-induced AKI may present alongside other drug toxicities, including optic neuritis (the most common serious adverse effect) 2, 4
- Renal function should be monitored regularly during ethambutol therapy, especially in patients with pre-existing renal impairment 1
Management and Prevention
- Ethambutol dosage must be adjusted in patients with renal insufficiency to prevent accumulation and toxicity 1
- For patients with end-stage renal disease, ethambutol should be administered at a dose of 15-20 mg/kg three times a week after dialysis 1
- Creatinine clearance or serum creatinine levels can serve as useful predictors for an individual patient's capacity to eliminate ethambutol 3
- If AKI is suspected to be caused by ethambutol, the drug should be discontinued and an alternative anti-tuberculosis medication considered 7
Important Considerations and Caveats
- While ethambutol can cause AKI, it is not among the most common nephrotoxic drugs (such as vancomycin, which is the primary nephrotoxin in many drug-induced AKI cases) 8
- Ethambutol-induced AKI may occur as part of a complex multineuropathy in patients with renal dysfunction, alongside optic neuritis and peripheral neuropathy 5
- The FDA label for ethambutol does not specifically list AKI as an adverse reaction, but does mention that the drug accumulates in patients with abnormal renal function 2
- Patients receiving ethambutol should be monitored not only for renal function but also for visual acuity changes, as optic neuritis is the most serious adverse effect 2