Saudi Journal of Kidney Diseases and Transplantation

: 2002  |  Volume : 13  |  Issue : 4  |  Page : 445--450

Post-transplant Tuberculosis

Paulose P Thomas 
 Department of Nephrology, Christian Medical College & Hospital, Vellore, Tamil Nadu, India

Correspondence Address:
Paulose P Thomas
Department of Nephrology, Christian Medical College & Hospital, Vellore, Tamil Nadu

How to cite this article:
Thomas PP. Post-transplant Tuberculosis.Saudi J Kidney Dis Transpl 2002;13:445-450

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Thomas PP. Post-transplant Tuberculosis. Saudi J Kidney Dis Transpl [serial online] 2002 [cited 2019 Aug 23 ];13:445-450
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Infectious complications are major causes of morbidity and mortality following organ transplantation. Increased frequency of tuberculosis has been demonstrated in solid organ transplant recipients. This has been attributed to the immunosuppressive agents used after transplantation. Most cases of tuberculosis after renal transplantation are due to reactivation of old dormant tuber­culosis. [1] Hence the incidence of post transplant tuberculosis can vary and can be expected to be more frequent in those countries of South East Asia, East Asia, South America and Africa where tuberculosis is more common in addition to China and Russia. The reported prevalence of post transplant tuberculosis is low in countries where this disease is not very common in the general population. The prevalence is 1% in Germany, [2] 1.7% in UK, [3] 2-3.1% in Eastern Europe, [4],[5] 2.4-3.6% in South America, [6],[7] 3.5% in Saudi Arabia, [1] 4.2% in Spain, [8] 4.1­5.8% in Turkey, [9],[10] 4.5-4.9% in South Africa [11],[12] and 9.5-14.7% in India. [13],[14],[15] The prevalence is 5-50 times more than in general population. [1],[7],[8]

 Risk Factors

Opportunistic infections, such as tuber­culosis, usually occur after six months of renal transplantation. Rubin identified these patients as those with serum creatinine concentration higher than 176 µgm/L (2 mg/dl), those on a daily prednisone dose of more than 20 mg, those receiving multiple anti­rejection therapies and patients with chronic viral infections such as Hepatitis C. [16] In a multivariate analysis, it was found that patients on cyclosporine immunosuppression had the highest risk of developing tuber­culosis with a relative risk of 2.5. Patients with diabetes mellitus had a relative risk of 2.2 and those with chronic liver disease had a relative risk of 1.7 for developing post transplant tuberculosis. [13] The transplanted kidney has been suspected to transmit tuberculosis. [17] Disseminated tuberculosis occurred in allograft recipients of kidneys procured from a donor who was found to have tuberculosis subsequently. [18]

 Clinical Features

Symptoms and signs of tuberculosis that are usually obvious in the normal host can be subtle in the immunosuppressed transplant recipient. Fever, cough and infiltrates on chest x-ray are the usual presenting features. [19] Pyrexia of unknown origin (PUO) may be the presentation in 15.7-68% of the patients. [13],[14],[20],[21] The involvement was pulmonary in 40.2-63% [1],[20] and disseminated in 19.3-38.7%. [1],[13],[22] In another study, the majority of patients with tuberculosis after transplantation had high intermittent fever, while the majority of patients with tuber­culosis on hemodialysis had persistent low­grade fever. [14] Tubercular peritonitis is an unusual presentation after transplantation unlike in hemodialysis patients. [14] Tuber­culous involvement is pulmonary in most post transplant patients as compared to predominant lymph nodal involvement in patients on hemodialysis. [23] Some patients may reveal granulomatous interstitial nephritis on renal biopsy. [24] The diagnosis is suspected and established only retros­pectively following clinical response to empiric anti tubercular treatment of PUO in 15.7% or of pleural effusion or pulmonary lesion in 10.2%. [13] There is an increased incidence of atypical mycobacterial infection among kidney transplant recipients. [3] Atypical mycobacteria were responsible for 29% of disseminated infections, 8% of pulmonary infections and all cases of cutaneous and articular tuberculosis.[1] Some patients may present with rectal bleeding and tuberculosis may be diagnosed on hemicolectomy and colonic biopsy. [25],[26] Rarely, it can present with acute hepatitis, [27] tuberculous meningo-encephalitis, or bowel perforation. Non-healing skin ulcer, pyomyositis and cerebral abscess are other rare presenting diagnosis. Chest radiograph findings revealed consolidation in 64%, miliary pattern in 18%, pleural effusion in 13.6%, tuberculoma and cavitation in 9% of the cases. [11] It was diagnosed in the first year after transplantation in 18-58% of the patients. [22],[28] Post transplant tuberculosis occurs earlier in cyclosporine treated patients as compared to those receiving prednisone and azathioprine for immunosuppression. In patients receiving immunosuppressive therapy with prednisolone and azathioprine, only 14.7% of tuberculosis cases occurred within one year, while in patients on cyclosporine 65% of the cases occurred within one year of transplantation. [29] In another report, 35% of tuberculosis occurring in patients on cyclosporine was disseminated, while all patients receiving azathioprine and prednisone had exclusively pulmonary disease. [7] The reason for the early occurrence and dissemi­nated nature of post transplant tuberculosis in patients on cyclosporine is not known. It is possible that cyclosporine, by down regulating the release of IL2 and TNF alpha, depresses lymphocyte proliferation and macrophage function leading to occurrence of tuberculosis. In one report, 57% of patients with post transplant tuberculosis also had other significant infections such as CMV, Nocardia, Pneumocystis or disseminated Herpes simplex [6] and hence co-infections should be excluded in all patients.


It is important to have a high index of suspicion in an appropriate clinical setting as late diagnosis due the slow growth of the bacteria in culture and delay in instituting [30],[31] treatment may be fatal.Temporary effervescence following antibiotic therapy with ofloxacin can contribute to the fatal diagnostic delay and death. [32] Early broncho alveolar lavage (BAL) may help in diagnosis and treatment. [33],[34] In a group of 199 patients who were either sputum negative for acid fast bacillus (AFB) or had had no expectoration, AFB was identified in gastric aspirate of 23 patients. BAL only revealed an additional 3 cases of tuberculosis. The remaining patients on follow up had no evidence of tuberculosis. [35] Thus the sensitivity of the test is 88.5% and hence useful in an area of high endemicity. The specificity of the test has to be established. Use of polymerase chain reaction may assist in the rapid detection of mycobacteria from body fluids or tissue samples. [36]


The mortality of tuberculosis after renal transplantation varies from 14.3 to 31.9%. [4],[5],[9],[13],[22],[28] The mortality rate from disseminated disease was 37% and from all other forms of tuberculosis was 11%. [1] In another study, 31.9% patients with post transplant tuberculosis died, 10.2% due to the post transplant tuberculosis itself and 6.6% due to other infections associated with tuberculosis. [13]

Tuberculosis following bone marrow transplantation (BMT)

Tuberculosis has been reported in solid organ transplantations other than the kidneys. Tuberculosis occurred in 4.9% of orthotopic liver transplantation. [12] Of five BMT series with a total of more than 5,000 patients, only 10 cases of Mycobacterium tuberculosis infection were described, with an overall incidence of 0.19%. [19] Relative risk for tuberculosis was 23.7 in allogenic BMT, 4.9 for total body irradiation and 3.6 for graft-versus-host disease. [19] The low prevalence of post transplant tuberculosis after BMT may be due to shorter duration of immunosuppression used in these patients.


Active infection by M. tuberculosis should be treated with four anti-tuberculous drugs in view of the emergence of isoniazid resistant and multi drug resistant tuber­culosis. [37] It is recommended to start with isoniazid, pyrazinamide, ethambutol, and ofloxacin or streptomycin. Rifampicin can be used instead of ofloxacin or strepto­mycin but it should be remembered that rifampicin can accelerate the hepatic metabolism of cyclosporine, tacrolimus, sirolimus and prednisolone so that rejection can be a sequela to the treatment of tuberculosis. [38] In bone marrow transplant recipients, this might aggravate graft versus host disease. [39] Rejection occurred in 5 of 10 patients on cyclosporine who were treated with rifampicin despite increasing the dose of cyclosporine in eight. [6] Use of rifampicin necessitated a mean of 2-fold increase in the cyclosporine dose. [10] In another study of 6 patients on cyclosporine and rifampicin, the total daily dose of cyclosporine had to be increased 3-5 fold, with the frequency of administration increased from twice to thrice daily. With this regimen, satisfactory cyclosporine levels were attained and there was no adverse effect on graft function. [40] The accelerated glucocorticoid metabolism with rifampicin has been known to cause graft rejection even in pre-cyclosporine era. [41] Hence the dose of steroids should also be doubled. Rifampicin co-administration caused the abrupt decrease in tacrolimus blood concentrations, leading to an appro­ximate tenfold increase in its daily dose. [42]

Because of the known cyclosporine­lowering effect of rifampicin resulting in increased cost of immunosuppressive therapy, patients were treated successfully with rifampicin-sparing therapy. [14] A four-drug regime without rifampicin given for 18 months is effective for pulmonary tuber­culosis in patients on cyclosporine. [43] Some authors have suggested that immunosup­pression should be stopped as part of the overall therapy of tuberculosis and that loss of allograft is generally of secondary importance. [44] This is neither practical in countries where post transplant tuberculosis is common nor necessary in view of the drugs that are available for treatment of tuberculosis. Isoniazid does not affect the bioavailability of cyclosporine. [45] However, hepatotoxiciy of the drugs should be closely monitored. Sensitivity test should be followed up as drug resistance may occur. [35],[46] Drugs such as clarithromycin effective against atypical mycobacterial infection such as M. avium can be administered to patients on rifampicin as it partially neutralizes the effect of rifampicin on cytochrome P4503A. [47],[48]

Hepatotoxicity of antitubercular drugs

Hepatotoxicity occurred in 10-33% patients on antituberculous therapy. [7],[10],[20] Hepato­toxicity occurred in 50% of patients receiving four or more antituberculous drugs compared to 21% in patients receiving three drugs. [20] Hence liver functions should be closely monitored after starting antitubercular therapy.

Isoniazid Prophylaxis

Many physicians use chemoprophylaxis with isoniazid. The duration of prophylaxis may be 12 to 18 months. In a study of 633 renal transplant recipients, mycobacterial infections did not occur in any of the patients receiving isoniazid prophylaxis, though it occurred in 6 of the 27 patients not receiving chemoprophylaxis. [3] In another study, tuberculosis occurred in Asian dialysis patients but not in Asian transplant recipients as the latter were on isoniazid prophy­laxis. [31] A double blind placebo controlled trial of isoniazid prophylaxis showed a trend towards lower risk of tuberculosis. Unfortunately due to the high incidence of hepatitis in the study population the drug had to discontinued in many patients. [49] It appears that the risk of renal transplant recipients developing serious hepatotoxicity with the administration of isoniazid is low and not different from normal individuals. [50] Atypical mycobacteria, which accounts for 10% of infection, may not be susceptible to isoniazid and hence these infections may not be prevented by isoniazid prophylaxis. Secondary prophylaxis for the duration of immunosuppressive regime may be desirable.


The varied presentation of tuberculosis after transplantation is a challenge to the diagnostic ability of the physician. Early diagnosis and effective therapy can subs­tantially reduce the morbidity and mortality from this condition. One should be aware of the interaction between drugs used against tuberculosis and for immunosuppression. Efficacy of preventive measures need to be evaluated in specific populations at high risk for post transplant tuberculosis.


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