RetourPatients with chronic renal failure (CRF) have more frequent adverse events and higher mortality rates than patients without CRF. This has been attributed to increased host susceptibility from the cellular immunosuppressive effects of CRF and to social determinants of health among those with CRF (85).
The severity of renal insufficiency is classified using creatinine clearance: it is mild when the rate of clearance is 60–120 mL/minute, moderate at 30–59 mL/minute, severe at 10–29 mL/minute and very severe at below 10 mL/minute. According to some experts, for patients with DS-TB on dialysis, a thrice-weekly dosing of pyrazinamide and ethambutol should be administered after the dialysis cycle (61, 85). Creatinine clearance is calculated using the following formula:
body weight (kg) × (140 minus age in years) × 0.85 (in women) / 72 × creatinine value.
Dose adjustments in adults with creatinine clearance below 30 mL/minute are as follows (unless otherwise indicated):
- Pyrazinamide: 25–35 mg/kg per dose, three times per week after dialysis.
- Ethambutol: 15–25 mg/kg per dose, three times per week after dialysis.
- Rifapentine and moxifloxacin, which are both used in regimens for DS-TB, do not require renal dose adjustment (18, 86).
Experts recommend close monitoring of creatinine every week or every 2 weeks, and adequate hydration (70). Given the frequent occurrence of electrolyte disturbances in CRF, weekly monitoring of electrolytes is also recommended.
In the case of severe hypokalaemia, treatment is with intravenous potassium chloride (KCl) at 10 mEq/ hour⁻¹ (10 mEq of KCl will raise the serum potassium by 0.1 mEq/L⁻¹). If the potassium level is low, checking the magnesium is recommended by experts; if this is not possible, empirical treatment with magnesium (i.e. magnesium gluconate at 1000 mg twice daily) should be considered in all cases of hypokalaemia. The use of spironolactone, 25 mg daily, is suggested in refractory cases (70).
Given the risk of QT prolongation (particularly due to moxifloxacin) and electrolyte imbalance, an ECG should be performed, taking into account that hypokalaemia may be refractory if the concurrent hypomagnesaemia is not corrected; the risk is higher if the intensive phase of treatment is prolonged for any reason; and electrolyte disturbances are reversible, although the disturbance might last weeks or months.
Implementation considerations
- Both the diagnosis of CRF and the treatment of TB in patients with CRF are challenging. There is little evidence to support evidence-based guidance for these patients.
- Given the complexities of the management of TB disease in patients with CRF, a close collaboration between infectious disease specialists, pulmonologists and nephrologists in this patient population is necessary. A TB consilium to support the management of people with TB that is difficult to treat may be of help (62, 73).