From the Guidelines
Starting anti-tuberculous treatment in patients with chronic kidney disease (CKD) requires careful dose adjustments and monitoring due to altered drug metabolism and increased risk of toxicity, with the general approach involving either estimating or measuring creatinine clearance to guide dosing recommendations 1. When initiating treatment, it is essential to consider the patient's glomerular filtration rate (GFR) to determine the appropriate dosing regimen.
- For patients with mild to moderate CKD (GFR >30 mL/min), standard doses of isoniazid (300 mg daily) and rifampin (600 mg daily) can be used as they are primarily metabolized by the liver 1.
- However, pyrazinamide should be dosed at 25-35 mg/kg three times weekly instead of daily, and ethambutol should be reduced to 15-25 mg/kg three times weekly to avoid accumulation of toxic metabolites 1.
- For severe CKD (GFR <30 mL/min) or dialysis patients, isoniazid remains at 300 mg daily, rifampin at 600 mg daily, but pyrazinamide should be 25 mg/kg three times weekly, and ethambutol 15 mg/kg three times weekly 1. It is crucial to administer medications after dialysis sessions to prevent drug removal and to facilitate direct observation therapy (DOT) 1.
- Close monitoring of liver function tests is essential as CKD patients have an increased risk of drug-induced hepatotoxicity.
- Additionally, supplementation with pyridoxine (vitamin B6, 25-50 mg daily) is crucial to prevent isoniazid-induced peripheral neuropathy, which CKD patients are particularly susceptible to.
- Regular monitoring of visual acuity and color discrimination is necessary due to the increased risk of ethambutol-related optic neuritis in these patients. The key to successful treatment is careful dose adjustment, regular monitoring, and supplementation to minimize the risk of toxicity and ensure optimal treatment outcomes in patients with CKD 1.
From the Research
Adjusting Drug Doses in CKD
To start anti-tuberculous treatment in a patient with Chronic Kidney Disease (CKD), it is crucial to consider the adjustment of drug doses.
- Drugs excreted by the kidney require dose reduction in CKD, as stated in 2.
- The adjustment depends on the severity of the disease and the proportion of the drug eliminated by the kidneys.
- The estimated glomerular filtration rate (eGFR) can guide dose adjustment in patients with stable kidney function.
Considerations for Drug Dosing
- At extremes of body mass, the eGFR can under- or overestimate kidney function, and it may need to be adjusted for body surface area, particularly for drugs with a narrow therapeutic range or requiring a minimum concentration to be effective, as mentioned in 2.
- Close monitoring of drug effect and toxicity is also needed and can be supported by therapeutic drug monitoring.
- For short courses of drugs with a wide therapeutic index, dose adjustment may not be needed, as stated in 2.
General Principles for CKD Management
- Medication dosing errors are a significant problem in patients with CKD, and adequate renal function is essential to avoid toxicity, as highlighted in 3.
- Patients with renal impairment often have alterations in their pharmacokinetic and pharmacodynamic parameters.
- The clearance of drugs eliminated primarily by renal filtration is decreased by renal disease, and special consideration should be taken when these drugs are prescribed to patients with impaired renal function.
Treatment of CKD
- Treatment of CKD can slow its progression to end-stage renal disease (ESRD), but the therapies remain limited, as discussed in 4.
- Blood pressure control using angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs) has the greatest weight of evidence.
- Glycemic control in diabetes seems likely to retard progression.
- Several metabolic disturbances of CKD may prove to be useful therapeutic targets but have been insufficiently tested.
Recent Advances in CKD Treatment
- New drug classes to augment renin-angiotensin-aldosterone system (RAAS) inhibitors as the standard of care have scarcely met their primary endpoints until recently, as mentioned in 5.
- Contemporary data suggest that augmenting RAAS inhibitors with new drug classes has the potential to improve clinical outcomes in a broad range of patients with CKD.
- Significant reductions in the risk of kidney failure were observed in trials evaluating the RAAS inhibitors and sodium-glucose co-transporter 2 (SGLT2) inhibitors.