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Bts Guidelines

Bts Guidelines

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How should we treat tuberculosis in adult patients...
Te aim o this review is to high‑
light the key messages rom the 2010 British To‑racic Society (BS) Guidelines or the preventionand management o 
 Mycobacterium tuberculosis
ection and disease in adult patients with chron‑
ic kidney disease (CKD),
and to give some in‑
ormation on the background leading to the rec‑
ommendations. It is not intended as a substi‑
tute or the ull guidelines, which can be accessed
at www.brit‑thoracic.org.uk/tuberculosis/tuber
culosis‑guidelines.aspx. It is strongly recommend‑
ed that clinicians aced with tuberculosis (B)
in a patient with advanced kidney disease reer di‑rectly to the guidelines or advice. Te recommen‑
dations are based on the best evidence available or,
where evidence is lacking, the advantages and dis‑
advantages o possible options or management
are discussed. Te advice given cannot be ully
comprehensive and there will always be patients
who do not t into the categories used. Much o 
clinical practice has developed rom experience
over many years and is not based on concrete
evidence rom trials. Tis kind o inormation is
also valuable, however, when discussing possibleadvice. As there is little or no evidence to inormwhen to screen or latent B inection (LBI), or
example, we have discussed the merits and dis‑
advantages o various options and have suggest‑
ed a rational approach, but it is or the individualclinician to make a judgment based on the partic‑
ular circumstances (s)he encounters.
It is likely that B will be seen more
requently in patients with CKD as people rom
How should we treat tuberculosis in adultpatients with chronic kidney disease?
Key messages from the British Thoracic Society Guidelines
Heather J. Milburn
Department of Respiratory Medicine, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom
Correspondence to:
Heather J. Milburn, MSc, MD, FRCP,Chest Clinic, Guy’s Hospital, GreatMaze Pond, London SE1 9RT, UK,phone: +44-207-188-5847,fax: +44-207-188-1289,e-mail: heather.milburn@gstt.nhs.uk
August 2, 2010.
August 2, 2010.
Conflict of interests: none declared.
Pol Arch Med Wewn. 2010;120 (10): 417-422Copyright by Medycyna Praktyczna,Kraków 2010
This review highlights the key messages from the 2010 British Thoracic Society Guidelines on
the management of
 Mycobacterium tuberculosis
infection and disease in adult patients with chronic
kidney disease. These guidelines were developed in response to many requests for advice from
respiratory and infectious diseases physicians who treat patients with tuberculosis, as there was
very little information available to help clinicians manage the disease in this population of often
very sick patients. Renal units in the United Kingdom were prescribing variable chemoprophylaxisregimens that frequently had no basis in evidence, and drug doses used to treat tuberculosis wereoften inappropriate because of clinicians’ natural concern about poisoning a patient with little or norenal function. The guidelines address these issues together with when and how to screen for latentinfection and the different needs of patients with renal impairment, those needing dialysis and thosewith a transplanted kidney. It became very clear in compiling these guidelines that there is a short-age of both background information on rates of tuberculosis in such patients in countries with low
background prevalence, and good randomized controlled trials of treatment regimens. Wherever
possible, the recommendations made are evidence-based, but this was not always available. This
review gives a summary of those recommendations and reiterates some of the important messages;
in particular, tuberculosis should be managed with the full involvement of the chest or infectiousdiseases physician who is the local lead for this important infection.
KEy WoRds
chronic kidneydisease, guidelines,tuberculosis
2010; 120 (10)
low levels. Te quality o evidence in this eld is
generally limited, with much based on case se‑
ries rather than RCs, and this is reected in 13o the 22 recommendations being graded D andonly 6 graded A.Levels o renal impairment in CKD have been
graded according to the criteria used by the Renal
 Association (UK) and are shown in the
What i the extent f the prblem f tuberculi
in chronic kidney disease?
Immunodeciency isa eature o CKD and this is urther compoundedby immunosuppressive therapy, making these pa‑tients more susceptible to reactivation o LBI ornew inection. Identiying patients at risk o B isnot always straightorward, and diagnosing activedisease can be delayed as the clinical presentationmay be uncharacteristic. Extrapulmonary disease,
particularly peritoneal disease, is relatively com‑mon and symptoms may be nonspecic.
Both CKD and B are more common in Asians
and black people than in the indigenous white
population in the UK,
but there is little inorma‑tion on the prevalence o B in CKD in countrieswith low background prevalence. Most o the pub‑lished case series are rom areas o the world with
high background rates o B, and reported case
rates are enormously variable but always high. In
attempting to quantiy the risk o developing ac‑tive B, we have used the relative risks reported
by NICE:
× 20 or patients with CKD or on dialy‑sis, and × 37 or renal transplant recipients. Tesegures are, however, based on a small series rom
and management o rejection ollowingtransplant has been rened considerably since
then, leading to a rise in inective complications.
It is likely, thereore, that this risk has increased
over time, and new studies are needed rom coun‑tries in Europe and North America with relativelylow background rates o B. Tere have been veryew studies in patients on peritoneal dialysis and
case rates are dicult to determine.
When and hw huld we creen fr latent tuber‑
culi infectin?
Given the substantially in‑
creased risk o active B in patients with CKD,
on dialysis or awaiting transplant, there is clearly
a need to try to reduce that risk. Tere are, how‑
ever, conicting data on when and how these pa‑
tients should be screened or LBI. Some groups
recommend tuberculin skin testing (S) or all
with CKD or as evaluation o potential trans‑
plant recipients,
but, because o underlyingimmunodeciency, this test lacks sensitivity in
these patients, with reported anergy rates o up to50%.
A positive test can be helpul but a negative
result cannot be assumed to be a true negative.
Te intereron gamma release assays (IGRA) have
not been ully evaluated in these patients, but
the limited evidence to date suggests that both
the QuantiFERON‑Gold tests (Cellestis, Austra‑
lia) and the ‑SPO.
(Oxord Immunotec, UK)are probably more useul screening tools or LBIin this patient group than the S. Indeterminate
the areas o the world with high background lev‑
els o B are also at increased risk o CKD.
Al‑though the management o uncomplicated pul‑monary B is well established in patients with
intact renal unction, evidence or management
o this disease in patients with CKD, on dialy‑
sis or ollowing renal transplantation, is sparse
and oten conicting. Tis lack o clarity has led
to increased requests or advice rom respirato‑ry and inectious diseases physicians who man‑
age B in these patients.
In 2008, the Joint uberculosis Committee
(JC) o the BS set up a working group to exam‑
ine the available evidence and produce compre‑
hensive guidance on screening or active B dis‑
ease and latent inection, together with manage‑
ment o these conditions in adult patients with
CKD, on dialysis and ollowing renal transplanta‑tion. In addition to several chest physicians with
experience in both the management o B and
the production o guidelines, the group included
renal physicians representing the Renal Associa‑
tion (United Kingdom [UK]), a microbiologist, in‑
ectious diseases physician, and pharmacologist.
Te JC and BS have been responsible or sev‑
eral other well‑respected guidelines relating tothe management o B,
and we hope the cur‑
rent guidelines will be similarly useul. Tey are
based on current practice in the UK but should be
equally relevant to the rest o Europe. In the UK,
the 1998 and 2000 BS guidelines were largely
superseded by the National Institute or ClinicalExcellence (NICE) guidelines in 2006,
but these
gave very little help on how to manage B in pa‑
tients with renal disease. Te American Torac‑ic Society had a larger section on treatment o 
B in renal disease in their 2003 B guidelines,
 and we reerred to these and incorporated some
o the recommendations, particularly those re‑
garding drug dosage. Te new BS guidelines havealso, however, given recommendations on screen‑ing and management o LBI and prophylaxis or
patients going on to transplantation.
Each recommendation in the guidelines isgraded by the strength o the supporting evi‑
dence using the revised Scottish Intercollegiate
Guidelines Network grading system. Levels o ev‑
idence are graded rom 1++ (“high quality meta‑‑analyses, systematic reviews o randomized con‑
trolled trials [RCs] or RCs with very low risk
o bias”) through to 4 (“expert opinion”), and
recommendations graded rom A through to D,
where A indicates high levels o evidence and D
Grades of renal impairmentstage 1 CKD: normal creatinine clearance and function but urinary tractabnormality, e.g., polycystic kidney, structural abnormalitystage 2 CKD: creatinine clearance 60–90 ml/minstage 3 CKD: creatinine clearance 30–60 ml/minstage 4 CKD: creatinine clearance 15–30 ml/minstage 5 CKD: creatinine clearance <15 ml/min with or without dialysisAbbreviations: CKD – chronic kidney disease
How should we treat tuberculosis in adult patients...
a chemoprophylactic regimen should be takenwith the involvement o a B specialist. Someimportant recommendations are made on dos‑
ages to dispel myths about dose reductions. Iso‑
niazid and riampicin can generally be used innormal doses in CKD, during dialysis or ollow‑
ing renal transplantation. Adequate regimens
given are: 6 months isoniazid (300 mg) daily, or
15 mg/kg 3 × per week (max. 900 mg) in stages 4and 5 CKD and dialysis, plus pyridoxine 10–25 mg
daily; 3 months riampicin plus isoniazid plus
pyridoxine in normal daily doses or weight; 4–6
months riampicin alone in normal daily doses
or weight.
Long‑term use o isoniazid is not recommend‑
ed. Tere is no evidence to support use o lower
doses as these are inadequate or treatment o LBI and lead to lower peak levels and possible
development o drug resistance. Vigilance should
always be maintained or signs o toxic side e‑
ects or the possible development o active B in
these patients.
Makig a iagi  active tuberculi
pulmonary B is common in renal patients, oc‑curring in 30% to 50% o cases o B, and clas‑
sic symptoms are not always present. Peritoneal
disease has been reported to occur in 57% o pa‑tients on dialysis.
Te possibility o B should
always be considered in any patient with a chron‑ic cough, unexplained weight loss or night sweats,
a cloudy peritoneal dialysate, lymphadenopathy or
chronic site‑specic symptoms. Appearances on
a chest radiograph should be compared with pre‑
vious lms and, i new abnormalities are present,advice should be sought rom a respiratory physi‑cian. Every efort should be made to obtain a spec‑
imen or culture and sensitivity. Histological ap‑
pearances o granulomata, with or without ca‑
seation or necrosis, are helpul, but a portion o 
all biopsy specimens should be sent in a plainpot (without ormalin) to the microbiology lab‑oratory or culture. Patients producing sputum
should be asked or 3 consecutive early morningspecimens or direct smear, culture, and sensitiv‑
ity. New chest radiograph abnormalities should
prompt additional investigations i sputum is
not available, such as induced sputum or exi‑
ble bronchoscopy. Mediastinal lymph nodes can
be assessed by endobronchial ultrasound‑guidedtransbronchial needle aspiration or mediastinos‑
copy, depending on local availability.
optimal management f tuberculi in renal
Patients ound or suspected o having
active pulmonary B should be isolated, preer‑
ably in negative pressure acilities. Positive pres‑
sure rooms should never be used or these pa‑
tients, particularly on renal units, as the inec‑tion could be disseminated to other vulnerable
patients.Te pharmacological properties o the antitu‑berculous drugs have been extensively reviewed,
but clear guidance on dosing, dosage schedule,assays are, however, more likely in this popula‑
tion, and there is scant evidence on negative pre‑
dictive values. It is thereore important to inter‑pret them in the light o previous history o B,
oreign travel, ethnic and environmental back‑
ground, and radiographic changes.
Screening o all patients with CKD, or even just
those on hemo‑ or peritoneal dialysis, would be
time consuming and expensive and unlikely to
be cost‑efective. It is recommended that screen‑ing in this group should be by good clinical prac‑
tice o detailing any history o prior B and its
treatment, B contact, a clinical examination,and a chest radiograph in any patient at high
risk (those o Asian or Arican ethnic origin and
anyone born in an area o high background risk). An IGRA test, with or without a S, can be used
i there is concern, but routine assessment o 
these patients using these screening tests is not
recommended. Any patient with an abnormalchest radiograph consistent with previous B,
but who has been adequately treated, should be
monitored regularly, and renal physicians may
wish to seek advice rom the local respiratory orinectious diseases physician who is the lead orB. Neither the S nor IGRA tests are suitable
or such patients with a positive history as none
o them is able to distinguish between distant
and recent inection.
Te risk o developing active B ollowing renal
transplantation is particularly high, and screen‑
ing may be benecial in this group. Tis can be
achieved while the patient is on the waiting list
or transplantation so that chemoprophylaxis
may be given beore transplantation, reducing
the problematic drug interactions with posttrans‑
plant immunosuppression. Te guidelines givetables or individual risk assessments. In gener‑al, these show that all black and Asian patients
and those born overseas should be screened and
considered or prophylaxis, either beore or a‑
ter transplant. In many renal units, the current
practice is to give blanket chemoprophylaxis toall at‑risk transplant recipients without assess‑
ment. Inevitably, this means that some patientswill receive chemoprophylaxis without evidence
o LBI. Whether or not this has any advantages
over screening and targeted treatment is, how‑
ever, unknown.
Hw hul we give chemprphlaxi?
prophylaxis or B itsel carries a risk, particularlyo hepatitis, and the rates o drug‑induced hepati‑
tis rom various regimens are given in the guide‑lines. Tese rates are, however, taken rom stud‑
ies in populations with intact renal unction, and
it is possible that they may be diferent in the re‑
nally impaired. In patients at low risk o LBI andwhere there is no evidence rom a positive S or
IGRA test, the risk o hepatitis rom chemopro‑
phylaxis oten outweighs that o development o active B, thus mitigating against routine chemo‑
prophylaxis or all transplant recipients. Gen‑
erally, it is recommended that the decision on

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