Can Anti-Tuberculosis Treatment (ATT) be continued in patients with Chronic Kidney Disease (CKD)?

Can Anti-Tuberculosis Treatment Be Continued in Chronic Kidney Disease?

Yes, anti-tuberculosis treatment (ATT) should be continued in patients with chronic kidney disease (CKD), but requires specific dose adjustments based on creatinine clearance, particularly for ethambutol and pyrazinamide. 1

Core Treatment Approach

Patients with CKD should receive the standard 6-month tuberculosis regimen (isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and rifampin for 4 months), with dosing modifications based on renal function. 1

• The standard regimen remains effective in CKD patients when appropriately dose-adjusted, with similar therapeutic outcomes to those with normal kidney function 2
• Treatment should not be withheld or delayed due to CKD, as tuberculosis poses significant mortality risk 1

Specific Dosing Adjustments by Drug

Drugs Requiring Dose Modification

For patients with creatinine clearance <30 mL/min or on hemodialysis:

• Ethambutol: Change from daily dosing to three times weekly (not dose reduction) 1, 3
• Pyrazinamide: Increase dosing interval to three times weekly 1
• These medications are primarily renally cleared and require interval adjustments rather than dose reductions to avoid subtherapeutic levels 3

Drugs NOT Requiring Adjustment

• Isoniazid: No dose adjustment needed (primarily hepatically metabolized) 1
• Rifampin: No dose adjustment needed (primarily hepatically metabolized) 1

Timing of Administration for Hemodialysis Patients

All anti-tuberculosis drugs should be administered after hemodialysis sessions to:

• Facilitate directly observed therapy 1
• Avoid premature drug removal during dialysis 1, 3
• Ensure adequate drug concentrations 3

Critical Monitoring Requirements

Enhanced surveillance is mandatory in CKD patients due to increased risk of adverse drug reactions:

• Adverse events occur in approximately 48% of CKD patients versus 14% in those with normal kidney function 4
• CKD is an independent predictor of adverse drug reactions (OR 4.96) 4
• More severe adverse events occur in CKD patients (32.6% vs 15.1% in normal kidney function) 4

Specific Adverse Events to Monitor

• Hepatobiliary toxicity: Most common (30.6% in CKD vs 8.9% in normal function) 4
• Neuropsychiatric effects: Particularly with isoniazid (10.6% vs 1.2%) 4
• Renal toxicity: Rifampin can cause acute interstitial nephritis, crescentic glomerulonephritis, or acute tubular necrosis 5
• Pyrazinamide-induced hyperuricemia: Can precipitate acute gout in CKD patients 5

Monitoring Strategy

Implement frequent clinical and laboratory monitoring:

• Baseline: Liver function tests, complete blood count, creatinine clearance calculation 1
• Serial monitoring: AST/ALT, creatinine, complete blood count at minimum every 2-4 weeks 1
• For cycloserine or ethambutol: Monitor serum drug concentrations to avoid toxicity 1
• Clinical assessment for symptoms of hepatitis, neuropathy, visual changes, and rash 1, 4

Special Considerations for Severe CKD

For patients with creatinine clearance <30 mL/min:

• Use creatinine clearance (Cockcroft-Gault equation), not eGFR, for dosing decisions 3
• Severe CKD stage is a significant risk factor for regimen change (OR 5.92) 2
• Consider therapeutic drug monitoring for ethambutol to ensure adequate levels without toxicity 1

Common Pitfalls to Avoid

• Never reduce the dose of ethambutol or pyrazinamide—increase the dosing interval instead 1, 3
• Do not use eGFR values without converting to absolute clearance for medication dosing 3
• Avoid administering medications before hemodialysis sessions 1, 3
• Do not discontinue rifampin or isoniazid due to minor gastrointestinal side effects; these are the most effective drugs and should be continued whenever possible 1
• Do not assume standard dosing is safe in CKD—even with dose adjustments, adverse events remain more common 2, 4

Treatment Duration

• Standard 6-month regimen is appropriate for most CKD patients with drug-susceptible tuberculosis 1
• Consider extending to 9 months if cavitary disease is present with positive cultures at 2 months 1
• No routine extension of therapy is needed solely based on CKD status 1