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Year : 2013  |  Volume : 12  |  Issue : 3  |  Page : 143-147  

Peculiarities of tuberculosis in kidney transplant recipients

Department of Medicine, Bayero University/AKTH, Kano, Nigeria

Date of Web Publication5-Sep-2013

Correspondence Address:
Bappa Adamu
Nephrology Unit, Department of Medicine, Aminu Kano Teaching Hospital
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1596-3519.117620

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Renal transplant is becoming increasingly available in developing countries. Significant advances have been made globally since the first successful kidney transplant in 1954, with the advent of newer, more effective and more selective immunosuppressants. As a result, allograft and patient survival has increased, leaving infection and malignancy as major challenges. The incidence rate of tuberculsis in renal transplant recipients is directly proportional to the prevalence in the general population with the developing countries having the highest rates. The objective of this paper is to review the existing literature on post renal transplant tuberculosis with a view to highlighting its peculiarities compared to tuberculosis in the general population.
Several databases (Medline, EMBASE, Cochrane data base, Google Scholar and AJOL) were searched for articles using the key words Tuberculosis (MESH), Renal (OR Kidney), AND transplant. Hand search was also made of reference list of retrieved articles. Full text of relevant original articles were retrieved and appraised.
Several studies have demonstrated increased risk of tuberculosis in renal transplant recipients, especially in developing countries. Tuberculosis in renal transplant recipients has peculiarities such as difficulty in diagnosing latent TB, atypical presentations, increased risk of dissemination, increased mortality and interactions of anti-Tb drugs with transplant medications.
Clinicians managing renal transplant recipients especially in developing countries should have a high index of suspicion for TB and be aware of its peculiarities in this patient population.

   Abstract in French 

Transplantation rénale devient de plus en plus disponible dans les pays en développement. Des avancées significatives ont été apportées à l'échelle mondiale depuis le premier rein réussi transplant en 1954, avec l'avènement de nouveaux immunosuppresseurs plus efficaces et plus sélectives. En conséquence, survie allogreffe et patient a augmenté, laissant l'infection et la malignité des défis aussi majeurs. Le taux d'incidence de tuberculsis chez des receveurs de transplantation rénale est directement proportionnel à la prévalence dans la population générale, avec les pays en développement ayant les taux les plus élevés. L'objectif de cet article est d'examiner la littérature existante sur le post transplantation rénale la tuberculose en vue de mettre en évidence ses particularités par rapport à la tuberculose dans la population générale. Plusieurs bases de données (Medline, EMBASE, base de données de Cochrane Google Scholar et AJOL) ont effectué une recherche pour articles à l'aide de la clé des mots la tuberculose (MESH), rénaux (rein ou), AND transplantation. Fouille manuelle a été effectuée aussi de la liste de référence des articles récupérées. Texte intégral des articles originaux pertinents ont été récupérée et évalué. Plusieurs études ont démontré un risque accru de tuberculose chez des receveurs de transplantation rénale, en particulier dans les pays en développement. La tuberculose chez des receveurs de transplantation rénale a des particularités comme la difficulté à diagnostiquer une tuberculose latente, présentations atypiques, un risque accru de diffusion, une mortalité accrue et interactions des médicaments anti-TB avec transplantation médicaments. Les cliniciens gestion des greffés rénaux notamment dans les pays en développement devraient ont un indice élevé de suspicion de tuberculose et être conscient de ses particularités dans cette population de patients.
Mots clés: Les pays en développement, greffe de rein tuberculose

Keywords: Developing countries, kidney transplant, tuberculosis

How to cite this article:
Adamu B. Peculiarities of tuberculosis in kidney transplant recipients. Ann Afr Med 2013;12:143-7

How to cite this URL:
Adamu B. Peculiarities of tuberculosis in kidney transplant recipients. Ann Afr Med [serial online] 2013 [cited 2022 Sep 30];12:143-7. Available from:

   Introduction Top

Kidney transplant is increasingly becoming available in developing countries. Indeed in 2004, three of the top five countries performing the greatest number of kidney transplant procedures were developing countries (India, Brazil and China). [1] In Nigeria, following the first successful kidney transplant in a private hospital in 2000, [2] several government hospitals have initiated kidney transplant activities. [3],[4],[5],[6],[7] Tuberculosis (TB) poses peculiar challenges in the post-transplant setting especially in developing countries where the burden is high. The aim of this review is to highlight the peculiarities of TB after kidney transplant especially as it applies to developing countries.

   Increased Risk of Development of TB in Kidney Transplant Recipients Top

One of the several peculiarities of TB in kidney transplant recipients [Table 1] is the increased risk of development of TB compared to the general population. The risk is directly proportional to the prevalence of TB in the general population with rates of TB in renal transplant populations of 0.5-1.0% reported in North America, 0.7-5% in Europe and 5-15% in India and Pakistan. [8],[9] This represents a 50 to 100-fold increase in the frequency of TB compared to the general population in the respective geographic regions. [10] Most cases of TB infections in kidney transplant recipients (KTRs) occur as a result of reactivation of quiescent foci of Mycobacterium tuberculosis that persist after initial asymptomatic infection [11] which explains why the prevalence of TB in KTRs is directly proportional to the prevalence in the general population. However, other potential routes of infection in KTRs include transmission by an infected graft or transmission from actively infected persons post-transplant. The increased risk of TB in KTRs is mainly as a result of iatrogenic immunosupression caused by post-transplant medications. Indeed, more potent immunosuppressant medications such as tacrolimus and mycophenolate mofetil have been shown to be associated with the development of TB earlier in the transplant period compared to other immunosupressants such as azathioprine and cyclosporine. [12]
Table 1: Peculiarities of TB in KTRs and their clinical implications

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The markedly increased risk of TB in KTRs makes it pertinent for all clinicians vested with the care of these patients to have high index of suspicion of TB for early detection and treatment.

   Difficulty in Diagnosis of Latent TB Top

Since most cases of TB in KTRs occur as a result of reactivation of latent infection, screening and treatment of latent TB in End Stage Renal Disease (ESRD) patients pre-transplant as well as post-transplant would have provided a good opportunity of the control of TB in these patient populations. Unfortunately, diagnosis of latent TB is fraught with difficulties both in pre-transplant as well as transplant recipients. Cutaneous anergy is reportedly high in ESRD patients and KTRs which can lead to false negative tuberculin reactivity test (Mantoux test). Machiraju et al found higher rates of anergy and lower rates of tuberculin reactivity in Indian ESRD patients compared to healthy controls. [13] In the same study the authours found that pre-transplant mantoux positivity has low sensitivity and specificity for predicting post-transplant tuberculosis. Another peculiarity of diagnosis of latent TB in transplant patients is that it requires an induration of only 5mm on a tuberculin test (because of iatrogenic immunosuppression post-transplant), not the 10mm induration as in the general population or dialysis patients. [8]

Despite the limitation of tuberculin test, clinical practice guidelines such as the European Best Practice Guidelines for Renal Transplantation and the American Society of Transplantation Guidelines for the Prevention and Management of Infectious Complications of Solid Organ Transplantation have recommended use of prophylactic isoniazid in patients with a past or current positive tuberculin skin test, and/or a history of TB without adequate documented treatment. [8],[14]

Interferon-gamma release assays such as T-SPOT. TB and QuantiFERON are an alternative to the tuberculin skin test for detecting latent TB infection in the general population. Unfortunately, their sensitivity and specificity have not been systematically evaluated in KTRs. Current evidence from studies on chronic kidney disease (CKD) stage five patients suggest important limitations for detecting latent TB infection which does not support their routine use in this patient population at present. [15],[16],[17],[18]

   Uncertainty of Effectiveness of Universal Anti-TB Prophylaxis in KTRs Top

Considering the very high risk of TB in KTRs and the unreliability of the diagnosis of latent TB infection in stage five CKD and KTRs, it looks reasonable to give universal prophylaxis for TB in post transplant period when there is highest immunosupression (first six months to one year) particularly in developing countries. Randomized controlled trials carried out in India and Pakistan have evaluated the benefit of prophylactic treatment with isoniazid for KTRs. [19],[20],[21],[22] Results of these studies suggest reduced risk of TB in patients who are treated with Isoniazid. However, these studies should be interpreted with caution as they are relatively small studies, open-labelled, with no placebo control and therefore are susceptible to bias, especially detection bias. Despite the limitations of these trials, the overall evidence supports the use of isoniazid prophylaxis in KTRs in TB endemic regions of the world. A systematic review and meta-analysis of these trials and other observational studies, by Currie et al concluded that isoniazid is valuable for TB prophylaxis in KTRs at risk of active TB infection. [23] Another on-going meta-analysis [24] will possibly further clarify the evidence especially if there are any new trials published after the meta-analysis by Currie et al. [23] In addition, several observational studies have demonstrated benefits of anti-TB prophylaxis in renal transplant recipients. [25],[26],[27],[28]

One factor against universal prophylaxis for TB in KTRs is that some observational studies showed no benefit of prophylaxis. [29],[30] Other factors against universal prophylaxis include potential hepatotoxicity of Isoniazid, development of resistance, and increased pill burden in these patients who are already on many medications.

Larger randomized controlled trials with placebo control and adequate blinding are needed to clarify the benefits and harms of TB prophylaxis in KTRs, considering the global importance of TB and the markedly increased risk in KTRs.

   Difficulty and Delay in Diagnosis of Clinical TB Top

Diagnosis of active TB in transplant patients is the same as in the general population, requiring confirmation by the demonstration of acid fast bacilli (AFB) in study materials, its growth in special culture media, demonstration of caeseating granulomata with or without AFB in histological materials, and more recently, the use of polymerase chain reaction (PCR). While establishing the diagnosis may be straight forward in some cases, [31] t may be delayed or difficult to establish in KTRs because of some peculiarities. As a result of drug induced imminosupression, symptoms may be attenuated, leading to delayed diagnosis. [32],[33] There are many reports of TB co-existing with other infections such as fungal infections, cytomegalo virus infection, as well malignancies such as Kaposi's sarcoma, which may all lead to atypical presentations and therefore delayed or difficult diagnosis. [34],[35],[36]

   Drug Interactions between anti-TB and Immunosupressants and Consequent Graft Loss Top

Another peculiarity of TB in KTRs is the interaction of anti-TB medications with immunosuppressants. Rifampicin for example, is an inducer of cytochrome P450 micro enzymes, leading to reduced levels of calcineurin inhibitors, mammalian target of rapamycin inhibitors and steroids. [37] In one study, this was associated with a 30% incidence of graft rejection and 20% incidence of graft loss. [38] In order to minimize this untoward effect, several steps have been recommended. First, blood levels of calcineurin inhibitors and mammalian target of rapamycin inhibitors should be closely monitored during treatment with rifampicin. [10] Secondly, rifabutin can be substituted for rifampicin since rifabutin achieves similar therapeutic efficacy while minimizing the potential for drug-drug interactions. [10] However, these two approaches may not be the best options in resource limited countries where rifabutin may not be available and frequent therapeutic drug monitoring adds additional cost of patient care. An alternative approach is rifampicin avoidance, in which rifampicin is substituted with a fluoroquinolone, and taken with isoniazid, ethambutol and pyrazinamide for the first two months of TB therapy. After this, pyrazinamide and ethambutol are stopped and fluoroquinolone and isoniazid continued for another 10-12 months. This approach has also been shown to be effective in the treatment TB in KTRs. [39],[40]

   Increased Morbidity and Mortality Top

Many studies have demonstrated that KTRs who develop TB are at increased risk of developing extra-pulmonary/disseminated TB and therefore increased morbidity. [32],[41],[42] Some studies report pulmonary TB as the commonest mode of presentation, but even in these reports, extra-pulmonary TB occurs in a significant proportion of patients. [33],[43],[44]

Mortality is also increased in KTRs with TB compared to TB in the general population, reportedly up to ten-fold. [10] Although there are no studies directly comparing mortality in kidney transplant and non-transplant populations, many observational studies from both developed and developing countries [26],[45],[46] revealed high mortality in KTRs with TB compared to TB mortality in the general population, with TB mortality up to 34.9% in one study. [26] The reported mortality rates in these studies are higher than TB mortality rates in the general population both in developed and developing countries. [47]

   Conclusion Top

Several studies have demonstrated increased risk of tuberculosis in renal transplant recipients, especially in developing countries. Tuberculosis in renal transplant recipients has peculiarities such as difficulty in diagnosing latent TB, atypical presentations, increased risk of dissemination, increased mortality and interactions of anti-Tb drugs with transplant medications.

Clinicians managing renal transplant recipients especially in developing countries should have a high index of suspicion for TB and be aware of its peculiarities in this patient population. Prophylaxis with Isoniazid in the first six months to one year after transplant should be given to KTRs in TB endemic regions of the world even though more trials are desirable in future to make this a strong evidence-based recommendation.

   References Top

1.Medina-Pestana JO, Duro-Garcia V. Strategies for establishing organ transplant programs in developing countries: The Latin America and Caribbean experience. Artif Organs 2006;30:498-500.  Back to cited text no. 1
2.Bamgboye EL. Barriers to a functional renal transplant program in developing countries. Ethn Dis 2009 Spring;19(1 Suppl 1):S1-56-9.  Back to cited text no. 2
3.Badmus TA, Arogundade FA, Sanusi AA, Akinsola WA, Adesunkanmi AR, Agbakwuru AO, et al. Kidney transplantation in a developing economy: Challenges and initial report of three cases at Ile Ife. Cent Afr J Med 2005;51:102-6.  Back to cited text no. 3
4.Bappa A, Abdu A, Borodo MM, Alhassan SU. Three years follow up of the first Renal Transplant in Aminu Kano Teaching Hospital. Tropical Journal of Nephrology 2006;1:29-32.  Back to cited text no. 4
5.Available from: [Last accessed on 2012 Mar 26].  Back to cited text no. 5
6.Available from: [Last accessed on 2012 Mar 29].  Back to cited text no. 6
7.Available from: [Last accessed on 2012 Mar 30].  Back to cited text no. 7
8.EBPG Expert Group on Renal Transplantation. European best practice guidelines for renal transplantation. Section IV: Long-term management of the transplant recipient. IV.7.2. Late infections. Tuberculosis. Nephrol Dial Transplant. 2002;17 Suppl 4:39-43.  Back to cited text no. 8
9.Jha V, Chugh KS. Posttransplant infections in the tropical countries. Artif Organs 2002;26:770-7.  Back to cited text no. 9
10.Kidney Disease: Improving Global Outcomes (KDIGO) Transplant Work Group. KDIGO clinical practice guideline for the care of kidney transplant recipients. Am J Transplant 2009;9 (Suppl 3):S1-155.  Back to cited text no. 10
11.Drobniewski FA, Ferguson J. Tuberculosis in renal transplant units. Nephrol Dial Transplant 1996;11:768-70.  Back to cited text no. 11
12.Atasever A, Bacakoglu F, Toz H, Basoglu OK, Duman S, Basak K, et al. Tuberculosis in renal transplant recipients on various immunosuppressive regimens. Nephrol Dial Transplant 2005;20:797-802.  Back to cited text no. 12
13.Shankar MS, Aravindan AN, Sohal PM, Kohli HS, Sud K, Gupta KL, et al. The prevalence of tuberculin sensitivity and anergy in chronic renal failure in an endemic area: Tuberculin test and the risk of post-transplant tuberculosis. Nephrol Dial Transplant 2005;20:2720-4.  Back to cited text no. 13
14.Subramanian A, Dorman S; AST Infectious Diseases Community of Practice. Mycobacterium tuberculosis in solid organ transplant recipients. Am J Transplant 2009;9(Suppl 4):S57-62.  Back to cited text no. 14
15.Triverio PA, Bridevaux PO, Roux-Lombard P, Niksic L, Rochat T, Martin PY, et al. Interferon gamma release assays versus tuberculin skin testing for detection of latent tuberculosis in chronic haemodialysis patients. Nephrol Dial Transplant 2009;24:1952-6.  Back to cited text no. 15
16.Hursitoglu M, Cikrikcioglu MA, Tukek T, Beycan I, Ahmedova N, Karacuha S, et al. Acute effect of low-flux hemodialysis process on the results of the interferon gamma-based QuantiFERON-TB Gold In-Tube test in end-stage renal disease patients. Transpl Infect Dis 2009;11:28-32.  Back to cited text no. 16
17.Winthrop KL, Nyendak M, Calvet H, Oh P, Lo M, Swarbrick G, et al. Interferon-gamma release assays for diagnosing mycobacterium tuberculosis infection in renal dialysis patients. Clin J Am Soc Nephrol 2008;3:1357-63.  Back to cited text no. 17
18.Kobashi Y, Mouri K, Obase Y, Fukuda M, Miyashita N, Oka M, et al. Clinical evaluation of QuantiFERON TB-2 G test for immunocompromised patients. Eur Respir J 2007;30:945-50.  Back to cited text no. 18
19.Agarwal SK, Gupta S, Dash SC, Bhowmik D, Tiwari SC. Prospective randomised trial of isoniazid prophylaxis in renal transplant recipient. Int Urol Nephrol 2004;36:425-31.  Back to cited text no. 19
20.Naqvi R, Naqvi A, Akhtar S, Ahmed E, Noor H, Saeed T, et al. Use of isoniazid chemoprophylaxis in renal transplant recipients. Nephrol Dial Transplant 2010;25:634-7.  Back to cited text no. 20
21.Vikrant S, Agarwal SK, Gupta S, Bhowmik D, Tiwari SC, Dash SC, et al. Prospective randomized control trial of isoniazid chemoprophylaxis during renal replacement therapy. Tranpl Infect Dis 2005;7:99-108.  Back to cited text no. 21
22.John GT, Thomas PP, Thomas M, Jeyaseelan L, Jacob CK, Shastry JC. A double-blind randomized controlled trial of primary isoniazid prophylaxis in dialysis and transplant patients. Transplantation 1994;57:1683-4.  Back to cited text no. 22
23.Currie AC, Knight SR, Morris PJ. Tuberculosis in Renal Transplant Recipients: TheEvidence for Prophylaxis. Transplantation 2010;90(7):695-704.  Back to cited text no. 23
24.Adamu B, Abdu A, Abba AA, Borodo MM, Tleyieh IM. Antibiotic prophylaxis for preventing post solid organ transplant tuberculosis. Cochrane Database Syst Rev 2010, Issue 7. Art. No.: CD008597. DOI: 10.1002/14651858.CD008597.   Back to cited text no. 24
25.Higgins RM, Cahn AP, Porter D, Richardson AJ, Mitchell RG, Hopkin JM, et al. Mycobacterial infections after renal transplantation. Q J Med 1991;78:145-53.  Back to cited text no. 25
26.Matuck TA, Brasil P, Alvarenga Mde F, Morgado L, Rels MD, da Costa AC, et al. Tuberculosis in renal transplants in Rio de Janeiro. Transplant Proc 2004;36:905-6.  Back to cited text no. 26
27.Apaydin S, Altiparmak MR, Serdengeçti K, Ataman R, Oztürk R, Erek E. Mycobacterium tuberculosis infections after renal transplantation. Scand J Infect Dis 2000;32:501-5.  Back to cited text no. 27
28.Sayiner A, Ece T, Duman S, Yildiz A, Ozkahya M, Kiliçaslan Z, et al. Tuberculosis in renal transplant recipients. Transplantation 1999;68:1268-71.  Back to cited text no. 28
29.Yildiz A, Sever MS, Türkmen A, Ecder T, Bes¸is¸ik F, Tabak L, et al. Tuberculosis after renal transplantation: Experience of one Turkish centre. Nephrol Dial Transplant 1998;13:1872-5.  Back to cited text no. 29
30.Spence RK, Dafoe DC, Rabin G, Grossman RA, Naji A, Barker CF, et al. Mycobacterial infections in renal allograft recipients. Arch Surg 1983;118:356-9.  Back to cited text no. 30
31.Abdu A, Adamu B, Sani MU, Mohammed AZ, Borodo MM. Post kidney transplant tuberculosis in Nigeria: A case report. Niger J Med 2008;17:217-9.  Back to cited text no. 31
32.Canet E, Dantal J, Blancho G, Hourmant M, Coupel S. Tuberculosis following kidney transplantation: Clinical features and outcome. A French multicentre experience in the last 20 years. Nephrol Dial Transplant 2011;26:3773-8.  Back to cited text no. 32
33.Chen CH, Lian JD, Cheng CH, Wu MJ, Lee WC, Shu KH. Mycobacterium tuberculosis infection following renal transplantation in Taiwan. Transpl Infect Dis 2006;8:148-56.  Back to cited text no. 33
34.Alshaebi F, Adamu B, Alghareeb W. Concurrent Kaposi′s sarcoma, tuberculosis, and allograft dysfunction in a renal transplant patient. Saudi J Kidney Dis Transpl 2009;20:270-3  Back to cited text no. 34
35.Ram R, Swarnalatha G, Prasad N, Dakshinamurty KV. Tuberculosis in renal transplant recipients. Transpl Infect Dis 2007;9:97-101.  Back to cited text no. 35
36.Chen SY, Wang CX, Chen LZ, Fei JG, Deng SX, Qiu J, et al. Tuberculosis in southern Chinese renal-transplant recipients. Clin Transplant 2008;22:780-4.  Back to cited text no. 36
37.Aguado JM, Torre-Cisneros J, Fortun J, Benito N, Meije Y, Doblas A, et al. Tuberculosis in solid-organ transplant recipients: Consensus statement of the group for the study of infection in transplant recipients (GESITRA) of the Spanish Society of Infectious Diseases and Clinical Microbiology. Clin Infect Dis 2009;48:1276-84.  Back to cited text no. 37
38.Singh N, Paterson DL. Mycobacterium tuberculosis infection in solid-organ transplant recipients: Impact and implications for management. Clin Infect Dis 1998;27:1266-77.  Back to cited text no. 38
39.Jha V, Sakhuja V, Gupta D, Krishna VS, Chakrabarti A, Joshi K, et al. Successful management of pulmonary tuberculosis in renal allograft recipients in a single center. Kidney Int 1999;56:1944-50.  Back to cited text no. 39
40.Vachharajani TJ, Oza UG, Phadke AG, Kirpalani AL. Tuberculosis in renal transplant recipients: Rifampicin sparing treatment protocol. Int Urol Nephrol 2002;34:551-3.  Back to cited text no. 40
41.Guida JP, Bignotto Rosane D, Urbini-Santos C, Alves-Filho G, Ribeiro Resende M, Mazzali M. Tuberculosis in renal transplant recipients: A Brazilian center registry. Transplant Proc 2009;41:883-4.  Back to cited text no. 41
42.El-Agroudy AE, Refaie AF, Moussa OM, Ghoneim MA. Tuberculosis in Egyptian kidney transplant recipients: Study of clinical course and outcome. J Nephrol 2003;16:404-11.  Back to cited text no. 42
43.Rungruanghiranya S, Ekpanyaskul C, Jirasiritum S, Nilthong C, Pipatpanawong K, Mavichak V. Tuberculosis in Thai renal transplant recipients: A 15-year experience. Transplant Proc 2008;40:2376-9.  Back to cited text no. 43
44.García-Goez JF, Linares L, Benito N, Cervera C, Cofán F, Ricart MJ, et al. Tuberculosis in solid organ transplant recipients at a tertiary hospital in the last 20 years in Barcelona, Spain. Transplant Proc 2009;41:2268-70.  Back to cited text no. 44
45.Ghafari A, Makhdoomi K, Ahmadpoor P, Afshari AT, Fallah MM, Rezaee K. Tuberculosis in Iranian kidney transplant recipients: A single-center experience. Transplant Proc 2007;39:1008-11.  Back to cited text no. 45
46.Klote MM, Agodoa LY, Abbott K. Mycobacterium tuberculosis infection incidence in hospitalized renal transplant patients in the United States, 1998-2000. Am J Transplant 2004;4:1523-8.  Back to cited text no. 46
47.Glaziou P, Floyd K, Korenromp EL, Sismanidis C, Bierrenbach AL, Williams BG, et al. Lives saved by tuberculosis control and prospects for achieving the 2015 global target for reducing tuberculosis mortality. Bull World Health Organ 2011;89:573-82.  Back to cited text no. 47


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