Can ethambutol (anti-tuberculosis medication) be withheld in patients with Acute Kidney Injury (AKI)?

Ethambutol Management in Acute Kidney Injury

Ethambutol should not be withheld in patients with acute kidney injury (AKI), but the dosage must be adjusted based on renal function to prevent toxicity. 1, 2

Dosing Adjustments in Renal Impairment

• Ethambutol is cleared primarily by the kidneys, and its metabolites can accumulate in patients with renal insufficiency, requiring dose adjustment 3
• For patients with renal impairment, the dose or dosing interval should be adjusted when creatinine clearance is less than 70 ml/minute 3
• For patients with end-stage renal disease on dialysis, ethambutol should be administered at a reduced dose of 15-20 mg/kg three times weekly after dialysis 3, 2
• Marked accumulation of ethambutol has been demonstrated in patients with renal insufficiency, increasing risk of toxicity 4

Monitoring Requirements

• Baseline visual acuity testing (Snellen chart) and color discrimination testing (Ishihara tests) should be performed before starting treatment 3, 5
• Monthly monitoring of visual acuity and color discrimination is recommended for all patients with renal insufficiency receiving ethambutol 3, 5
• Renal function should be monitored regularly during ethambutol therapy, especially in patients with pre-existing renal impairment 1, 2
• Measuring serum ethambutol levels is recommended in patients with kidney dysfunction to prevent toxicity 5

Risk of Toxicity in Renal Impairment

• Pre-existing renal insufficiency significantly increases the risk of ethambutol toxicity, particularly ocular toxicity 1, 2, 5
• The most serious side effect is retrobulbar neuritis, which can lead to potentially irreversible vision loss if not promptly identified 5, 6
• Patients with end-stage renal disease on dialysis are at particularly high risk of developing severe and potentially irreversible ethambutol-induced optic neuritis 6, 7
• Higher doses (>30 mg/kg/day) further increase the risk of toxicity in patients with renal impairment 2, 5

Management Algorithm for Ethambutol in AKI

1. Assess severity of renal impairment by measuring creatinine clearance 3, 2
2. Adjust ethambutol dosage based on renal function:
   • For mild-moderate renal impairment: Reduce dose to 15 mg/kg/day 3, 8
   • For severe renal impairment: Consider 15-20 mg/kg three times weekly 3, 2
3. Perform baseline visual acuity and color discrimination testing 3, 5
4. Monitor monthly:
   • Visual acuity and color discrimination 3, 5
   • Renal function 1, 2
   • Ask about visual disturbances at each visit 3, 5
5. Discontinue ethambutol immediately and permanently at first sign of visual toxicity 3, 5

Important Considerations

• Ethambutol is included in initial TB treatment regimens primarily to prevent emergence of rifampin resistance when primary resistance to isoniazid may be present 3
• A study of renal function-based anti-TB drug dosage adjustments showed that proper dose adjustment in CKD patients resulted in similar therapeutic outcomes to those in patients without CKD 8
• However, adverse events requiring regimen changes were more common in patients with severe CKD, even with appropriate dose adjustments 8
• Patients with AKI may be at risk for additional nephrotoxicity from other anti-TB medications, such as rifampin 9, 10

Pitfalls to Avoid

• Never use standard doses of ethambutol in patients with renal impairment, as this can lead to drug accumulation and increased toxicity 3, 4
• Do not overlook the need for regular visual monitoring in patients with renal impairment receiving ethambutol 3, 5
• Avoid assuming that all visual changes are reversible; some patients with renal impairment may develop permanent visual impairment despite drug discontinuation 6, 7
• Do not continue ethambutol if any visual symptoms develop; the drug should be discontinued immediately and permanently 3, 5