What is the recommended anti-tuberculosis treatment (ATT) regimen for a patient with chronic kidney disease (CKD)?

Anti-Tuberculosis Treatment in Chronic Kidney Disease

For CKD patients with creatinine clearance <30 mL/min or on hemodialysis, use isoniazid and rifampin at standard daily doses, but switch pyrazinamide and ethambutol to three-times-weekly dosing at 25-35 mg/kg and 20-25 mg/kg respectively, with all medications given post-dialysis. 1

Core Dosing Strategy by Renal Function

Mild CKD (GFR 60-89 mL/min)

• Use standard anti-tuberculosis regimens without dose reduction 2
• Follow national guidelines for drug-susceptible TB with isoniazid, rifampin, pyrazinamide, and ethambutol at conventional doses 3, 4, 5

Moderate CKD (GFR 30-59 mL/min)

• Continue standard daily dosing for isoniazid and rifampin 1
• Begin monitoring more closely for drug accumulation, particularly with pyrazinamide and ethambutol 1

Severe CKD (GFR <30 mL/min) and Hemodialysis

• Isoniazid: 300 mg daily (standard dose) - hepatically metabolized, no adjustment needed 1, 3
• Rifampin: 600 mg daily (standard dose) - hepatically metabolized, no adjustment needed 1
• Pyrazinamide: 25-35 mg/kg three times weekly (NOT daily) - metabolites accumulate despite hepatic metabolism 1
• Ethambutol: 20-25 mg/kg three times weekly (NOT daily) - 80% renally cleared 1

Critical Principle: Extend Intervals, Never Reduce Doses

The fundamental error to avoid is reducing the milligram dose of pyrazinamide or ethambutol - you must extend the dosing interval instead to maintain therapeutic peak concentrations while preventing toxicity. 1 This approach preserves the concentration-dependent killing needed for bacterial eradication while allowing adequate time for drug clearance between doses 6.

Timing with Dialysis

• Administer all anti-tuberculosis medications immediately after hemodialysis sessions 1
• This prevents premature drug removal during dialysis and facilitates directly observed therapy 1
• Exception: Moxifloxacin (if used) can be given at any time as it is not significantly removed by dialysis 7

Fluoroquinolone Selection for Drug-Resistant TB

Moxifloxacin (Preferred in Severe CKD)

• Dose: 400 mg once daily without any adjustment for renal function 7
• Undergoes hepatic metabolism, maintaining standard dosing across all levels of renal impairment 7
• Can be administered at any time relative to dialysis 7
• Higher doses (600-800 mg daily) may be used for resistance, though long-term safety data are limited 7

Levofloxacin (Requires Complex Adjustment)

• Dose in severe CKD: 750-1000 mg three times weekly when creatinine clearance <50 mL/min 7
• 80% renal clearance necessitates careful dosing modifications 7
• Must be given post-dialysis if patient is on hemodialysis 6
• Avoid within 2 hours of antacids or divalent cations (calcium, magnesium, iron, aluminum) 6

Moxifloxacin is strongly preferred over levofloxacin in severe CKD because it eliminates the complexity of renal dose adjustments and maintains consistent therapeutic levels. 7

Injectable Agents (Second-Line)

• Streptomycin, kanamycin, amikacin, and capreomycin are essentially 100% renally excreted 1
• Require strict frequency reduction in CKD 1
• Generally avoided in severe renal impairment due to high nephrotoxicity and ototoxicity risk 1

Essential Monitoring Requirements

Before Treatment Initiation

• Calculate creatinine clearance - never assume normal serum creatinine indicates adequate renal function in elderly or sarcopenic patients 1
• Baseline visual acuity testing (for ethambutol monitoring) 1
• Baseline audiogram and vestibular testing (if injectable agents considered) 1
• Liver function tests 1

During Treatment

• Monthly renal function assessment 1
• Monthly questioning about visual symptoms (blurred vision, color discrimination changes) 1
• Serum drug concentration monitoring for ethambutol, cycloserine, or injectable agents if used 1
• Consider therapeutic drug monitoring in patients with borderline renal function or multiple comorbidities 6

Treatment Efficacy and Safety Data

A retrospective study of 241 pulmonary TB patients demonstrated that renal function-based dosage adjustments achieved similar therapeutic outcomes across all CKD severity groups, with 78% sputum culture conversion at 2 months and 5.8% TB-related mortality 8. However, adverse events requiring drug discontinuation were more frequent in severe CKD (P=0.051), and severe CKD stage was a significant risk factor for regimen change (OR=5.92) 8.

Common Pitfalls to Avoid

• Never reduce the milligram dose of pyrazinamide or ethambutol in CKD - extend the interval to three times weekly instead 1
• Do not assume normal creatinine means normal kidney function - calculate creatinine clearance, especially in elderly or low muscle mass patients 1
• Avoid restarting rifampin after acute kidney injury develops during treatment - two patients died from severe renal failure after rifampin rechallenge 9
• Do not give medications before dialysis - all TB drugs should be administered post-dialysis except moxifloxacin 1, 7

Alternative Regimens for Rifampin-Induced AKI

If acute interstitial nephritis develops (most commonly from rifampin), consider restarting anti-TB treatment without rifampin, substituting levofloxacin or moxifloxacin 9. Short-term steroid administration may be beneficial for pathologically confirmed acute interstitial nephritis 9. Twelve of 15 patients (80%) normalized renal function after restarting treatment without rifamicin 9.

Newer Regimens (BPaL/BPaLM)

For drug-resistant TB in CKD patients, the WHO's newer regimens (bedaquiline, pretomanid, linezolid, with or without moxifloxacin) are mostly safe due to dominant hepatic metabolism 10. Exercise caution with linezolid due to increased hematologic side effects and bedaquiline due to QTc prolongation risk 10.