Indian J Nephrol 2003;13: 69-71

69

ARTICLE

Treatment of tuberculosis in chronic renal failure,

maintenance dialysis and renal transplant
KK Malhotra
Senior Consultant and Head Department of Nephrology,
Pushpawati Singhania Research Institute, New Delhi 110017

Introduction
Host resistance to infection is primarily mediated by
cellular immunity which is deficient in patients with
chronic renal failure (CRF)1. The occurrence of infections
including tuberculosis (TB) is therefore high in such
patients. The incidence of TB in patients on maintenance
haemodialysis (MHD) has been reported to be 6 to 16
times that of general populations2. Most of MHD patients
are potential candidates for renal transplantation (RT)
and infected patients may carry the burden of TB during
the post-transplant period. Renal transplant recipients
are on various immunosuppressive drugs which causes 2.
additional risk to development of TB3,4. There is need for
proper investigations to detect TB in such patients; this
is especially so in endemic areas of TB. Principles of
anti-tubercular chemotherapy in patients of CRF, MHD
and RT include avoidance of nephrotoxic drugs,
modification of dose of drugs depending on the degree
of renal failure and attention to interactions between
immunosuppressive drugs and anti-tubercular drugs.
This article will discuss pharmacological and therapeutic 3.
principles of commonly employed anti-tubercular drugs
in CRF and RT recipients and the drug regimes followed
in such cases. It will also review current status of
chaemoprophylaxis in RT recipients.

Anti-tubercular drugs pharmacological and

therapeutic considerations

which it is acetylated. However, normal daily doses

of isoniazid (300 mg or 5-6 mg/kg) can be given in
patients with severe renal impairment as
administration of these doses in such cases will be
equivalent to 8-9 mg/kg which is well tolerated6. It
has been demonstrated that reducing isoniazid
doses to 200 mg/day results in significant reduced
therapeutic potency7. Keeping this background
information in mind, most clinicians do not alter
normal doses of isoniazid in patients of CRF and
MHD.
Rifamipicin The effects of renal impairment on
rifamipicin elimination are negligible at doses of 450
mg, modest at 600 mg and substantial at 900 mg6.
There is unanimous recommendation that rifampicin
doses need not be reduced below 600 mg/day.
Rifampin has been shown to cause acute interstitial
nephritis in some cases8 and can cause deterioration
of renal function. Hence patients on this drug should
be watched for this possible complication.
Ethambutal This drug makes a significant
contribution to preventing drug resistant failure and
is generally used during initial two months of
chemotherapy. About 80% of ingested dose of
ethambutal is excreted in urine and hence dose
reduction has been advocated in patients with
renal.impairment9. About 50% dose reduction is
advised in patients with creatinine clearance of less
than 10ml/min10. It has been observed that ocular
toxicity of the drug is dose dependent and must be
kept in mind during chemotherapy.

The commonly employed anti-tubercular drugs in

patients of CRF, MHD and RT are isoniazid, rifampicin,
ethambutal, pyrazinamide, streptomycin and fluoroquinolones (ofloxacin or ciprofloxacin). It will be desirable
to consider pharmacological and therapeutic principles 4. Pyrazinamide This drug is usually included in
management of TB during initial two months of
of above drugs.
treatment. It has been shown that thrice weekly
1. Isoniazid Oral absorption of isoniazid is excellent.
treatment is therapeutically more effective than daily
The primary metabolic route determining the rate
treatment11 and results in a greatly reduced risk of
at which it is eliminated from the body is acetylation5.
arthralgia. It is therefore advisable that patients of
There are differences in individuals in the rates at
CRF should be treated either thrice or twice weekly
doses of 40 mg or 60 mg/kg of the drug respectively.
Address for Correspondence:
For patients on MHD, it might be convenient to give
KK Malhotra
such doses approximately 24 hours before start of
Senior Consultant and Head
each dialysis session. Dose modification of the drug
Department of Nephrology,
is needed in cases of advanced renal failure (with
Pushpawati Singhania Research Institute,
creatinine clearance of less than 10 ml/min)10.
New Delhi 110017

Copyright 2003 by The Indian Society of Nephrology

70

Indian Journal of Nephrology

Indian J Nephrol 2003;13: 69-71

Table 1 : Dose modification of Anti-tubercular Drugs in Chronic Renal Failure10

Drugs

Dose for Normal

Renal Function

Dose modification for GFR (ml/min)

>50
10-50
<10

Isoniazid

300 mg q 24 hr

100%

100%

100%

Rifamipicin

600 mg q 24 hr

100%

100%

100%

Ethambutal

15 mg q 24 hr

100%

50-100%

50%

Pyrizinamide

15-30 mg q 24 hr

q 24 hr

q 24 hr

q 48-72 hr

Streptomycin

1 g q 24 hr

100%

q 24-72 hr

q 72-96 hr

Ofloxacin

400 mg q 24 hr

100%

50%

25%

Modified from Olyaei et al10

5. Streptomycin This drug is rarely used in treatment

of TB these days because of its nephrotoxicity and
other side effects. If the drug has to be used, its
dose must be reduced depending upon degree of
renal failure. It is recommended that 0.75 g to 0.5g
should be given twice or thrice weekly during first
two months of treatment. In patients on MHD doses
should be given 6 8 hours before each dialysis
session.
6. Fluoroquinolones (Ofloxacin or Ciprofloxacin)
These are second line anti-tubercular drugs and are
used either for drug-resistant TB or when first line
drugs cannot be used due to their side effects/
toxicity. These drugs are well absorbed orally and
distribute well to body fluids and tissues.
Mycrobacterial resistance to fluoroquinolones
develops rapidly and hence these drugs should be
used in selected situations as described above. Dose
adjustment is required in cases with renal
impairment 50% dose in patients with creatinine
clearance between 10-50 ml/min and 25% dose in
patients with creatinine clearance below 10 ml/min10.
Dose modification of antitubercular drugs in CRF has
been presented in Table 1 (Modified from Olyaei et al10).

Drug regime and duration of

anti-tubercular treatment
The drug regime for anti-tubercular drugs in CRF and
MHD are not well defined. The following regime is usually
employed Isoniazid, rifampicin and pyrizinamide are
given for first two months followed by isoniazid and
rifampicin for a minimum period of 10 months. Some

Copyright 2003 by The Indian Society of Nephrology

clinicians extend total period of chemotherapy for 18

months. If pyrazinamide cannot be used during initial
two months, this is usually replaced by ethambutal. If
tubercular infection is severe, four drug regime (isoniazid,
rifampicin, pyrazinamide and ethambutol) is used during
initial two months. Real problems in chemotherapy arise
when isiniazid or rifampicin can not be employed due to
their side effects (usually drug induced hepatitis) or
because of associated viral hepatitis which co-exists in
a considerable number of such patients. Under such
circumstances, one has to employ more toxic first line
drugs with or without second line drugs (ofloxacin or
ciprofloxacin).

Anti tubercular drugs in renal

transplant recipients
There are two types of renal transplant recipients (a)
Group in which TB was detected during pre-transplant
period (during MHD) and in which anti-TB treatment was
initiated during that period and needs continuation of
such treatment with some modifications. In most of such
cases renal function returns to normal after successful
RT and dose modification imposed because of CRF is
withdrawn. (b) Group in which TB manifests at variable
time periods after RT and anti-TB treatment has to be
initiated.
In all RT recipients drug interaction between anti-TB
drugs and immunosuppressive drugs need
consideration. Rifampicin is an inducer of enzymes
involved in hepatic metabolism of cortiosteroids and
therefore daily dose of corticosteroid need to be
increased to about one and half times its base line dose

Indian J Nephrol 2003;13: 69-71

Tuberculosis in dialysis and transplant patients

if rifampicin is used. Rifampicin lowers the blood level of

cyclosporin-A (CyA) by enhancing its hepatic
metabolism. Therefore blood levels of CyA need to be
monitored and its dose has to be increased accordingly.12
Isoniazid is also potential inducer of cytochrome P-450
and causes rapid metabolism of CyA and same
precaution of adjusting dose of CyA is required in
patients receiving isoniazid12. Ciprofloxacin and Ofloxacin
decrease metabolism of CyA and hence dose of CyA
has to be decreased in such patients.
The optimum duration of anti-TB treatment in RT is not
well defined. In most centers, treatment is given for a
minimum period of one year but some extend it for 18
months. Close watch has to be kept in all RT recipients
for recurrence of TB after discontinuation of
chemotherapy, as clinical features may be mild/vague
because of immunosuppression.

71

Chaemoprophylaxis in renal
transplant recipients
The role of isoniazid prophylaxis in RT recipients is still
debatable. In a double blind randomized controlled trial
of primary isoniazid prophylaxis in dialysis and transplant
patients, some degree of protection from TB was
observed. However no firm conclusion could be drawn
from this study because of high drop out rate on account
of high prevalence of viral hepatitis13. In another
prospective study from Delhi regarding effect of isoniazid
prophylaxis during renal replacement therapy (RRT)
there was a trend towards protection with isoniazid
prophylaxis but there was no statistically significant
effect14. As the incidence of viral hepatitis is high in
patients on RRT in India, there is difficulty in
interpretation of isoniazid induced hepatitis in such
cases.

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Copyright 2003 by The Indian Society of Nephrology