What are the recent tuberculosis (TB) treatment guidelines for a patient with chronic kidney disease (CKD) and an estimated glomerular filtration rate (eGFR) of 22 milliliters per minute (ml/min)?

TB Treatment in CKD with eGFR 22 ml/min

For a patient with chronic kidney disease and eGFR of 22 ml/min, use isoniazid (INH) 300 mg and rifampin (RIF) at standard daily doses, but administer pyrazinamide (PZA) and ethambutol (EMB) three times weekly instead of daily, with all medications given post-dialysis if the patient is on hemodialysis. 1

Core Dosing Principles for Severe CKD

With an eGFR of 22 ml/min (creatinine clearance <30 ml/min), increase the dosing interval rather than decrease the dose to maintain therapeutic peak serum concentrations while avoiding toxicity. 1

First-Line Drug Adjustments

INH and RIF:

• Use standard daily doses (INH 300 mg once daily, RIF standard dose) without adjustment 1
• Both are hepatically metabolized and not significantly affected by renal insufficiency 1
• RIF is not cleared by hemodialysis due to high molecular weight and protein binding 1

PZA and EMB:

• Administer three times weekly instead of daily 1
• PZA is hepatically metabolized, but its metabolites (pyrazinoic acid and 5-hydroxy-pyrazinoic acid) accumulate in renal insufficiency 1
• EMB is approximately 80% renally cleared and will accumulate with standard daily dosing 1
• PZA and EMB are cleared to varying degrees by hemodialysis 1

Post-dialysis administration is strongly preferred to facilitate directly observed therapy (DOT) and prevent premature drug clearance during dialysis. 1

Treatment Regimen Structure

For drug-susceptible TB with eGFR <30 ml/min:

• Intensive phase: INH + RIF daily, plus PZA + EMB three times weekly 1
• Continuation phase: INH + RIF daily (or three times weekly based on clinical response) 1
• Minimum duration: Consider extending treatment duration due to immunocompromised state associated with renal insufficiency 1

Critical Monitoring Requirements

Close monitoring is essential as TB patients with chronic renal failure have worse clinical outcomes than those without renal failure. 1

Baseline Assessment

• 24-hour urine collection may be needed for borderline renal function to accurately define the degree of renal insufficiency before making regimen changes 1
• Baseline visual acuity and color discrimination testing before EMB initiation (critical given renal impairment increases EMB toxicity risk) 1

Ongoing Surveillance

• Therapeutic drug monitoring (TDM): Measure serum concentrations at 2 and 6 hours after timed administration to optimize drug dosages, particularly for patients with borderline renal function 1
• Renal function: Monitor creatinine and eGFR regularly, as further decline may necessitate additional adjustments 2
• Hepatotoxicity monitoring: Drug-induced hepatitis is more common and severe in CKD patients (30.6% vs 8.9% in normal kidney function) 3
• Neuropsychiatric effects: More frequent in CKD (10.6% vs 1.2%), particularly with INH 3
• Visual monitoring: Monthly for EMB-related optic neuritis, which has higher risk with renal accumulation 1

Adverse Event Management

ADRs occur in 48% of CKD patients versus 13.7% in those with normal kidney function, and are more severe (32.6% vs 15.1%). 3 CKD is an independent predictor for ADRs (OR 4.96,95% CI: 2.79-8.82). 3

Most Common ADRs in CKD:

• Hepatobiliary (30.6%): Monitor liver enzymes closely; drug-induced hepatitis is a significant risk factor for regimen change (OR 35.6) 3, 2
• Neuropsychiatric (10.6%): Supplement with pyridoxine 25-50 mg/day with INH to prevent peripheral neuropathy 1
• Renal toxicity (5.3%): Rifampin can cause acute interstitial nephritis, crescentic glomerulonephritis, or acute tubular necrosis even in CKD patients 4
• Cutaneous reactions: Significant risk factor for regimen change (OR 17.4) 2

Management Strategy:

• Immediate discontinuation of the offending drug is essential to limit morbidity and mortality 4
• Consider TDM to reduce adverse events while maintaining efficacy 5
• Severe CKD stage is an independent risk factor for regimen change (OR 5.92) 2

Special Considerations for Hemodialysis Patients

If the patient progresses to hemodialysis:

• Administer all medications post-dialysis to avoid premature clearance and facilitate DOT 1
• PZA and its metabolites are cleared significantly by hemodialysis; INH and EMB are cleared to some degree 1
• Monitor for rifampin-induced accelerated hypertension and thrombocytopenia, which can occur in maintenance hemodialysis patients 4
• Supplemental dosing is not necessary if drugs are given post-dialysis 1

Drug-Resistant TB Considerations

For multidrug-resistant TB in patients with eGFR <30 ml/min:

• Fluoroquinolones: Levofloxacin requires greater dose adjustment than moxifloxacin due to higher renal clearance 1
• Injectable agents (streptomycin, kanamycin, amikacin, capreomycin): Require significant dose adjustment as kidneys excrete essentially all of these drugs; approximately 40% removed by hemodialysis 1
• Expert consultation is mandatory for second-line drug dosing in severe CKD 1

Efficacy Expectations

Despite dose adjustments, therapeutic outcomes remain similar to non-CKD patients when guidelines are followed:

• Sputum culture conversion rates at 2 months do not vary significantly by CKD severity (approximately 78%) 2
• In-hospital TB-related mortality does not differ significantly between CKD groups when appropriate dosing is used 2
• However, vigilance for ADRs is critical as they are substantially more frequent and may necessitate regimen changes 3, 2