HomeEnd-stage kidney disease requiring dialysis is a well-established risk factor for TB disease, with incidence rates 7 times higher than the general population.131–133 Evidence is emerging to suggest that TB risk is also increased in people with earlier stages of chronic kidney disease (CKD), with risk rising as estimated glomerular filtration rate drops below 50 ml/min.133–135
Susceptibility to TB in CKD appears multifactorial.136,137 People with CKD often have low 25-hydroxy vitamin D levels and higher rates of protein malnutrition. As uremic waste products accumulate in later stages of renal disease, a broad cellular immune dysfunction develops. The risk of TB may be compounded by associated co-morbid conditions such as diabetes and use of immune suppressive drugs.
The clinical presentation of TB in people with CKD is often insidious and atypical.136 Systemic symptoms, such as fever, anorexia and weight loss, may mimic uremia and can result in a delay of diagnosis. People with CKD frequently have extra-pulmonary TB, rather than the more recognizable pulmonary disease.138 Delayed recognition may contribute to the higher mortality rates seen in these populations.136
A special consideration in this population is to ensure renal-adjusted dosing for some TB drugs.136 Rifampin and INH are primarily metabolized and excreted through the liver with little urinary clearance. Thus, dose adjustment of these agents is not required for patients with renal insufficiency.138 Although PZA is also metabolized primarily through the liver, some of its metabolites are eliminated renally and so its dose should be adjusted in people with advanced CKD ((Stage 4/5, GFR < 30ml/min).138,139 Ethambutol (EMB) is mostly excreted unchanged by the kidneys and people with advanced CKD have substantially reduced clearance of the drug.140 Ethambutol-induced ocular toxicity is largely dose-related and so dose adjustment and regular visual acuity testing is necessary in those with advanced CKD.
Because therapeutic efficacy of both PZA and EMB appears dependent on peak concentrations, the dosing interval for both drugs should be extended in people with advanced kidney disease, rather than decreasing the dose administered.
There is insufficient evidence to guide dosing of people with moderate kidney disease (GFR 30-60mL/min). In this range, people should be monitored carefully for toxicity, and therapeutic drug monitoring might be necessary to guide appropriate dosing.
The mechanism of drug removal by peritoneal dialysis is not the same as by hemodialysis and so TB drug-dosing recommendations for people receiving hemodialysis may not necessarily apply. There is comparatively little clinical experience in TB drug-dose adjustment in people receiving peritoneal dialysis.141,142 Thus, people receiving peritoneal dialysis should be monitored carefully for drug toxicity and therapeutic drug monitoring may be necessary.
Treatment extension solely based on CKD is not recommended, as neither slower response to treatment nor higher relapse rates have been reported in these patients.
Recommendation
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We conditionally recommend, in people with advanced chronic kidney disease (Stage 4/5, GFR < 30ml/min), that dose intervals should be modified to three times weekly for pyrazinamide (25-30 mg/kg) and ethambutol (15-20 mg/kg) (poor evidence).
Good practice statement
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Pyrazinamide and ethambutol (and other first-line TB drugs) should be dosed after dialysis session in people on hemodialysis.
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