Treatment of Tuberculosis in Chronic Kidney Disease
Core Recommendation
For patients with CKD and drug-susceptible TB, use the standard rifampin-isoniazid-pyrazinamide-ethambutol regimen with dose adjustments based on creatinine clearance: rifampin and isoniazid require no adjustment, while pyrazinamide and ethambutol must be given three times weekly (not daily) when CrCl <30 mL/min. 1, 2
Initial Assessment and Renal Function Determination
Calculate actual creatinine clearance using a 24-hour urine collection if borderline renal function is suspected, as serum creatinine alone can be misleading, especially in elderly patients with reduced muscle mass who may have severe renal impairment despite "normal" creatinine values 2, 1
For patients with CrCl 30-50 mL/min, standard doses are used but measurement of serum concentrations at 2 and 6 hours after timed administration should be performed to optimize dosing 1, 2
Close monitoring is mandatory as TB patients with chronic renal failure have worse clinical outcomes than those without renal failure 2
Drug-Specific Dosing for CrCl <30 mL/min or Hemodialysis
No Dose Adjustment Required
Isoniazid: 300 mg once daily or 900 mg three times weekly - hepatically metabolized and not significantly affected by renal impairment 1, 2
Rifampin: 600 mg once daily or 600 mg three times weekly - hepatically metabolized and conventional dosing can be used 1, 2
Moxifloxacin (if needed): 400 mg once daily - undergoes less renal clearance than levofloxacin 1, 2
Dose Adjustment Required (Frequency Change)
Pyrazinamide: 25-35 mg/kg three times weekly (NOT daily) - metabolites (pyrazinoic acid and 5-hydroxy-pyrazinoic acid) accumulate in renal insufficiency 1, 2
Ethambutol: 20-25 mg/kg three times weekly (NOT daily) - approximately 80% renally cleared and will accumulate with daily dosing 1, 2
Levofloxacin (if needed): 750-1000 mg three times weekly (NOT daily) - undergoes greater renal clearance than moxifloxacin and requires dose adjustment 1, 2
Injectable Agents (if required for drug-resistant TB)
- Streptomycin, amikacin, kanamycin, capreomycin: 15 mg/kg two to three times weekly (NOT daily) - all require frequency adjustment 1
Critical Timing for Hemodialysis Patients
All anti-TB medications must be administered after hemodialysis on dialysis days to prevent premature drug clearance and facilitate directly observed therapy 1, 2. This is particularly important for pyrazinamide, which is cleared significantly by hemodialysis, while rifampin is not cleared by hemodialysis 1.
Therapeutic Drug Monitoring
Serum drug concentration monitoring should be performed to ensure adequate drug absorption without excessive accumulation, especially for pyrazinamide and ethambutol given their altered pharmacokinetics in renal impairment 1, 2. This is particularly important in patients with end-stage renal disease who often take multiple medications that interact with anti-TB drugs 1, 2.
Treatment Duration and Regimen Selection
The standard 6-month regimen (2 months intensive phase with 4 drugs, followed by 4 months continuation phase with rifampin and isoniazid) remains appropriate for drug-susceptible TB in CKD patients 1. For patients with GFR 60-89 mL/min, anti-tuberculosis regimen should be carried out according to national standards without reducing doses 3.
Multidrug-Resistant TB in CKD
For MDR/RR-TB patients with severe renal impairment, the WHO recommends:
Group A agents (levofloxacin or moxifloxacin, bedaquiline, linezolid) should be included with at least four effective agents in the intensive phase 1
Bedaquiline requires no dose adjustment in renal impairment 1
Linezolid: 600 mg daily (no adjustment needed) 1
Cycloserine: 250 mg once daily or 500 mg three times weekly with therapeutic drug monitoring 1
Kanamycin and capreomycin are not recommended for MDR/RR-TB patients on longer regimens 1
Common Pitfalls to Avoid
Never simply reduce doses - this lowers peak concentrations and compromises efficacy; instead, extend the dosing interval 2
Do not assume normal dosing is safe based on "normal" serum creatinine alone in elderly or low muscle mass patients 2
Do not give anti-TB drugs before hemodialysis - this wastes medication through dialytic clearance 2
Do not use daily dosing for pyrazinamide and ethambutol when CrCl <30 mL/min - accumulation will occur leading to toxicity 1, 2
Adverse Event Monitoring
Patients with severe CKD are at significantly increased risk for adverse events requiring regimen change, even with renal function-based dosage adjustment 4. Drug-induced hepatitis and cutaneous reactions are particularly common and are significant risk factors for regimen change (OR = 35.6 and 17.4, respectively) 4. Weekly liver function tests for the first two weeks, then at two-weekly intervals during the first two months of treatment are recommended 1.
Special Considerations
Renal function and proteinuria should be monitored carefully during the first few months of therapy, as rifampin and isoniazid can rarely cause minimal change disease with acute renal failure 5
For unconscious patients unable to swallow, isoniazid and rifampin can be given as syrup via nasogastric tube, or rifampin and isoniazid can be administered by intravenous infusion 1
All new dialysis patients should undergo interferon-gamma release assay testing for latent TB 6