CAT I ATT Regimen for CKD Patients
For CKD patients requiring Category I anti-tuberculosis treatment, use the standard four-drug regimen (isoniazid, rifampin, pyrazinamide, ethambutol) with dose adjustments based on creatinine clearance: maintain standard dosing for isoniazid and rifampin regardless of renal function, but reduce the frequency (not the dose) of pyrazinamide and ethambutol to three times weekly when creatinine clearance is <30 mL/min. 1
Core Regimen Components
Drugs Requiring No Adjustment
- Isoniazid: Use standard dosing of 300 mg once daily or 900 mg three times weekly, regardless of renal function 1
- Rifampin: Use standard dosing of 600 mg once daily or 600 mg three times weekly, regardless of renal function 1
- Both drugs are metabolized hepatically and do not require dose reduction in CKD 1
Drugs Requiring Frequency Adjustment
For patients with creatinine clearance <30 mL/min or on hemodialysis:
Pyrazinamide: 25-35 mg/kg three times weekly (NOT daily) 1
Ethambutol: 20-25 mg/kg three times weekly (NOT daily) 1
Critical Dosing Principle
The key principle is to extend the dosing interval rather than reduce the milligram dose. 1, 2 This maintains peak serum concentrations necessary for bactericidal activity while allowing adequate drug clearance between doses 1. Reducing the actual dose amount may compromise treatment efficacy 1, 2.
Monitoring Requirements
- Baseline assessment: Obtain creatinine clearance (24-hour urine collection may be needed for borderline function) 1
- Therapeutic drug monitoring: Consider measuring serum concentrations at 2 and 6 hours post-dose to optimize dosing, especially in patients with creatinine clearance 30-50 mL/min 1
- Regular monitoring: Assess renal function and drug toxicity throughout treatment 1
Timing of Administration
All anti-tuberculosis medications should be administered after hemodialysis on dialysis days 1. This approach:
- Facilitates directly observed therapy 1
- Prevents premature drug removal by dialysis 1
- Ensures adequate drug exposure 1
Special Considerations for Advanced CKD
For CKD Stage 4-5 (GFR <30 mL/min):
- Use three times weekly dosing for pyrazinamide and ethambutol 1
- Maintain daily or three times weekly dosing for isoniazid and rifampin 1
- Monitor closely as this population has higher TB-related mortality 3
For Hemodialysis Patients:
- Follow the same dosing adjustments as creatinine clearance <30 mL/min 1
- Pyrazinamide is significantly cleared by hemodialysis 1
- Isoniazid and ethambutol are cleared to some degree 1
- Rifampin is NOT cleared by hemodialysis 1
Common Pitfalls to Avoid
- Do not reduce the milligram dose of pyrazinamide or ethambutol—only extend the interval 1, 2
- Do not use daily dosing for pyrazinamide and ethambutol in severe CKD 1
- Do not administer drugs before dialysis as this leads to premature drug removal 1
- Do not assume standard dosing is safe for patients with creatinine clearance 30-50 mL/min without therapeutic drug monitoring 1
Treatment Duration
Standard 6-month regimen applies: 2 months intensive phase (all four drugs) followed by 4 months continuation phase (isoniazid and rifampin) 1. However, extrapulmonary TB is more common in CKD patients (60-75% of cases), and some forms may require extended therapy 4, 3.
Drug Interactions and Toxicity
- Aminoglycosides (streptomycin): If needed for drug-resistant TB, reduce frequency to 15 mg/kg two to three times weekly (not daily) in severe CKD 1
- Ethambutol: Monitor for optic neuritis, which may be more difficult to detect in patients with uremic complications 1
- Nephrotoxic agents: Avoid concurrent use of other nephrotoxic drugs when possible 1