Nephrotoxicity in Anti-Tuberculosis Treatment

Introduction to Nephrotoxicity

• Nephrotoxicity from anti-tuberculosis drugs is a significant cause of raised renal function tests in patients undergoing anti-tuberculosis treatment, with aminoglycosides being the primary culprits, according to the Centers for Disease Control and Prevention (CDC) 1
• Aminoglycosides, such as streptomycin, amikacin, and kanamycin, cause nephrotoxicity in 2-25% of patients, with capreomycin being the most nephrotoxic, as reported by the CDC 1

Risk Factors for Nephrotoxicity

• Pre-existing renal impairment, advanced age (>59 years), larger cumulative doses, concurrent use of other nephrotoxic agents, and dehydration are risk factors for nephrotoxicity, as identified by the CDC 1

Monitoring and Management

• The CDC recommends performing baseline renal function tests before starting anti-tuberculosis treatment and assessing for pre-existing risk factors, including age >59 years, diabetes mellitus, hypertension, and pre-existing renal disease 1
• Monthly assessment of renal function is recommended for all patients, with more frequent monitoring (every 1-2 weeks) for high-risk patients, such as those receiving aminoglycosides, patients with baseline renal impairment, and elderly patients, as suggested by the CDC 1
• The recommended monitoring schedule is as follows:

2

• Therapeutic drug monitoring is essential for amikacin therapy, with target peak levels of 25-35 μg/mL and trough levels of <5-10 μg/mL, as recommended by the American Thoracic Society 3

Dosing and Administration

• The recommended dose for adults with normal renal function is 15 mg/kg/day (maximum 1.0 g/day) administered as a single daily dose, with dose reduction to 10 mg/kg/day (maximum 750 mg) for patients over 59 years of age, as supported by the American Thoracic Society and the Centers for Disease Control and Prevention 3, 1
• For infants and children, the recommended dose is 15-30 mg/kg/day as a single daily dose, with a maximum dose of 1 gram per day, according to the American Thoracic Society, the CDC, and the Clinical Infectious Diseases society 3, 1, 4
• Patients with renal impairment require dose adjustment, with the American Thoracic Society recommending maintaining the dose at 12-15 mg/kg but extending the interval between doses to 2-3 times per week 3, 1

Contraindications and Interactions

• Amikacin is contraindicated in pregnancy due to the risk of fetal nephrotoxicity and congenital hearing loss, as stated by the American Thoracic Society and the British Thoracic Society guidelines 3, 2, 1
• Amikacin should not be used simultaneously with other aminoglycosides or nephrotoxic agents, and can interact with diuretics and bisphosphonates, increasing the risk of ototoxicity and hypocalcemia, as recommended by the British Thoracic Society guidelines 2, 1

Treatment Outcomes

• Single daily dosing has advantages, including higher peak concentrations that enhance concentration-dependent bactericidal effect while allowing longer drug-free periods to reduce toxicity, as supported by the CDC and the American Thoracic Society 1, 3
• Amikacin is more effective than kanamycin and capreomycin in the treatment of resistant tuberculosis, according to 5
• The Centers for Disease Control and Prevention recommends initially daily dosing (5-7 days/week), then reducing to 2-3 times weekly after 2-4 months or after culture conversion 3, 1