Abstract

 

Guidelines have been compiled by the Joint Tuberculosis Committee of the British Thoracic Society for the prevention and management of Mycobacterium tuberculosis infection and disease in patients with all grades of renal impairment.

 

Patients with renal disease are at increased risk of tuberculosis (TB). This is true for all patients with chronic kidney disease (CKD), but particularly so for those from ethnic minority groups who are both at increased risk of developing active TB disease and in whom the prevalence of CKD is also substantially higher. Despite this increased risk, there are few guidelines for the investigation and treatment of TB disease in CKD. Although there is broad agreement over drug treatment and its duration, there are differing views regarding dosing. There are no randomized controlled trials into outcomes in patients with advanced CKD, and little information specifically dealing with issues of immunosuppression and transplantation. The evidence to guide protocols for active case finding (screening) and treatment of latent disease is limited and there is variation in practice to approaches to prevent reactivation. Evidence consists of small prospective studies of haemodialysis clearance, pharmacokinetic studies of therapy in renal failure, retrospective observational data, case reports and expert opinion.

 

The objectives of these guidelines are to quantify the risks of developing active disease and to give advice where possible on the management of TB infection and disease in patients (1) with all stages of CKD; (2) on peritoneal dialysis and haemodialysis; and (3) with renal transplants. The risks of developing disease and the risks and benefits of treatment for latent TB infection are covered. These guidelines are intended to inform renal physicians and surgeons, respiratory physicians and infectious diseases physicians treating TB together with specialist nurses in those disciplines.

 

 

Evidence informing these guidelines supports the following:

 

Patients with chronic kidney disease (CKD), on dialysis and following transplantation are at significantly increased risk of tuberculosis (TB).

Patients born overseas who have been in the UK for <5 years, those of African, Asian, South American or Eastern European ethnicity and anyone with a history of contact with smear positive pulmonary disease have an additional significantly increased risk of TB.

Around 50% of patients with CKD have reduced skin test responsiveness to the tuberculin skin test; that is, freedom from TB cannot be inferred from a negative tuberculin skin test in a patient with CKD.

There is little or no evidence at present to answer the following points:

There is no evidence on when to screen for latent TB infection (LTBI) or which patients should receive chemoprophylaxis.

Supporting evidence for methods of screening for LTBI is limited.

There is inconsistency in published dosages, dose intervals and timing of doses for patients on dialysis.

 

 

All patients with chronic kidney disease (CKD) considered at risk for tuberculosis (TB) should have a history of prior TB or TB contact sought, any history of prior TB treatment checked (including drugs taken and treatment duration), an appropriate clinical examination, a chest x-ray and, if appropriate, an interferon gamma release assay (IGRA) test specific for Mycobacterium tuberculosis antigens (see text). (D)

 

Any patient with CKD with an abnormal chest x-ray consistent with past TB, or previous history of extrapulmonary TB but who has previously received adequate treatment should be monitored regularly and considered for referral to and assessment by a specialist with an interest in TB, either a thoracic or infectious diseases physician. (D)

 

Routine assessment of patients with CKD or those on haemodialysis or peritoneal dialysis with a tuberculin skin test (TST) or IGRA test is not recommended. Renal physicians may wish to assess individual patients at high risk of latent TB infection (LTBI) with an IGRA test (with or without a TST, a negative test being unhelpful) and discuss the results with a chest/infectious diseases specialist in TB. (D)

 

Patients on the waiting list for renal transplantation may be assessed with an IGRA test (with or without a TST, as above), giving the opportunity for chemoprophylaxis before transplantation. An individual risk assessment can be made (see below). In general, all black African and Asian patients born outside the UK should be screened and considered for chemoprophylaxis before or after transplantation. (D)

 

The decision on chemoprophylaxis regimen should be made by the thoracic or infectious disease physician after discussion with both the patient and renal team. (D)

 

In general, isoniazid and rifampicin can be used in normal doses in renal impairment, during dialysis and following transplantation (see below). (D)

 

For chemoprophylaxis, use 6 months of isoniazid 300 mg daily plus pyridoxine 10–25 mg daily, or isoniazid plus rifampicin (as Rifinah) plus pyridoxine for 3 months or rifampicin alone for 4–6 months. Any of these regimens is adequate for chemoprophylaxis. Long-term use of isoniazid is not recommended. (A)

 

There is no evidence to support chemoprophylaxis regimens of longer than 6 months for isoniazid alone, 3 months for isoniazid plus rifampicin, or 4–6 months for rifampicin alone. (A)

 

There is no evidence to support use of lower doses. These are inadequate for treatment of LTBI and lead to lower peak levels and possible development of drug resistance. (D)

 

If patients who have had chemoprophylaxis develop symptoms suggestive of clinical TB, they should be promptly and appropriately investigated. (A)

 

If active TB is suspected, every effort should be made to isolate an organism for sensitivity testing. (B)

 

Patients with active pulmonary disease should be isolated, preferably in negative pressure facilities. (D)

 

All cases of TB should be notified to the proper officer, usually the local consultant in Communicable Disease Control. (A)

 

Close cooperation between renal physicians and specialists in the management of TB is strongly recommended. (D)

 

Active TB should be excluded in patients with CKD by appropriate investigations in patients who have an abnormal chest x-ray or a history of prior pulmonary or extrapulmonary TB that has been either inadequately or not previously treated. Chemoprophylaxis should be given. (A)

 

TB should be considered in all patients with unexplained systemic or system-specific symptoms as extrapulmonary TB is common, particularly in patients on dialysis, with peritoneal TB being common in patients on chronic ambulatory peritoneal dialysis. (B)

 

Any patient with active TB, either pulmonary or non-pulmonary, should receive standard chemotherapy agents, albeit with dose interval modifications where appropriate (see text) and for standard duration as per the NICE guidelines. (A)

 

Peak and trough drug levels should be monitored, particularly for ethambutol and the aminoglycosides, especially if there is concern regarding over- and under-dosing. (D)

 

For patients with stages 4 and 5 CKD, dosing intervals should be increased to three times weekly for ethambutol, pyrazinamide and the aminoglycosides. (D)

For patients on haemodialysis, dosing intervals for ethambutol, pyrazinamide and the aminoglycosides should be increased to three times weekly to reduce the risk of drug accumulation and toxicity. (D)

 

Treatment can be given immediately after haemodialysis to avoid premature drug removal. With this strategy there is a possible risk of raised drug levels of ethambutol and pyrazinamide between dialysis sessions. Alternatively, treatment can be given 4–6 h before dialysis, increasing the possibility of premature drug removal but reducing possible ethambutol or pyrazinamide toxicity. The choice of strategy may be influenced by a need to ensure adherence (when post dialysis offers the opportunity for directly observed therapy), practical issues (post dialysis for morning shift patients) and expected pharmacokinetics or drug interactions. (D)

 

Rifampicin in particular can interact with immunosuppressive regimens, increasing the chance of graft rejection, and doses of mycophenolate mofetil, tacrolimus and ciclosporin may need adjustment. Corticosteroid doses should be doubled in patients receiving rifampicin. (B)

 

 

Heather Milburn, Neil Ashman, Peter Davies, Sarah Doffman, Francis Drobniewski, Saye Khoo, Peter Ormerod, Marlies Ostermann, Catherine Snelson. Guidelines for the prevention and management of Mycobacterium tuberculosis infection and disease in adult patients with chronic kidney disease. Thorax 2010;65:559-570.

http://thorax.bmj.com/content/65/6/559.long