Mycobacterium tuberculosis Infection in Renal Transplant Recipients

Mycobacterium tuberculosis Infection in Renal Transplant Recipients

Mycobacterium tuberculosis Infection in Renal Transplant Recipients I. Ergun, Y. Ekmekci, S. Sengul, S. Kutlay, F. Dede, B. Canbakan, and B. Erbay ABS...

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Mycobacterium tuberculosis Infection in Renal Transplant Recipients I. Ergun, Y. Ekmekci, S. Sengul, S. Kutlay, F. Dede, B. Canbakan, and B. Erbay ABSTRACT Mycobacterium tuberculosis (TB) infection is more common among renal allograft recipients compared with the general population due to immunosuppression. The epidemiological risk in a country is an important determinant of transplant TB after transplantation. We retrospectively analyzed 283 renal transplant recipients who underwent renal transplantation between 1990 and 2004. We evaluated the incidence, patient and disease characteristics, prognosis, and outcome of TB infection. Tuberculosis developed in 10 (seven men and three women of mean age of 41 ⫾ 9 years) among 283 patients (3.1%). All patients were culture-positive for M tuberculosis. Although pulmonary TB was the most common presentation in the general population, 50% of patients in the study group developed extrapulmonary TB. The mean elapsed time from renal transplantation was 38 months. Three patients (1%) developed TB in the first year after transplantation. All patients were treated with a quartet of anti-TB therapy. One patient developed isoniazidrelated reversible hepatotoxicity. No acute allograft rejection occurred during the anti-TB therapy. Two patients (20%) with pulmonary TB died due to dissemination of the disease. In conclusion, extrapulmonary presentations of TB are more common among renal transplant recipients with the increased risk of mortality.

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UBERCULOSIS (TB) is an important cause of mortality and morbidity among solid organ transplant recipients. Due to immunosuppression and recent development of newer potent immunosuppressive drugs, renal transplant recipients are more prone to both primary infections and reactivation of Mycobacterium tuberculosis compared with the general population (36- to 74-fold higher).1 M tuberculosis infection among renal transplant recipients presents important diagnostic difficulties because of the greater incidence of extrapulmonary involvement and the atypical presentation of the disease.2 In this study, we sought to assess the incidence, patient and disease characteristics, prognosis, and outcome of TB infection in renal transplant recipients.

PATIENTS AND METHODS We retrospectively analyzed 283 renal allograft recipients who underwent kidney transplantation between 1990 and 2004. Fortyfour had received a cadaveric (15.5%) and 239 of them, a living related (84.5%) allograft. The diagnosis of TB was based on microbiological growth in a culture of Lowenstein-Jensen medium. All patients had immunosuppression including corticosteroid ⫹ azathioprine/mycophenolate mofetil ⫹ cyclosporine/tacrolimus. Cadaveric allograft recipients also received antithymocyte globulin induction.

RESULTS

TB was diagnosed in 10 of 283 kidney allograft recipients (3.5%). The mean age of the study population was 30 ⫾ 10 years, whereas it was 41 ⫾ 9 years in the TB infection group (P ⬎ .05). Tuberculosis developed in seven men and three women patients. Two of them were recipients of cadaveric and eight of living related transplantations. The causes of chronic renal failure were glomerulonephritis in four patients, interstitial renal diseases in two patients, and other diseases/unknown etiologies in four patients. The incidence of TB was 3.5% in our population. The most common presentation was pulmonary TB (n ⫽ 5, 50%) with fewer cases of pleural TB (n ⫽ 2), intestinal TB (n ⫽ 1), peritoneal TB (n ⫽ 1), and otitis media (n ⫽ 1). The time between TB infection and renal transplantation was 38 months (range, 3 to 81 months). In 3 of 283 patients (1%), TB was diagnosed in the first year after transplantaFrom the Department of Nephrology, Ankara University School of Medicine, Ankara, Turkey. Address reprint requests to Dr Ihsan Ergun, MD, Department of Nephrology, Ankara University School of Medicine, Ibni Sina Hospital, Sihhiye, Ankara D6100, Turkey. E-mail: ihsanerg@ yahoo.com

0041-1345/06/$–see front matter doi:10.1016/j.transproceed.2006.03.029

© 2006 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710

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Transplantation Proceedings, 38, 1344 –1345 (2006)

MYCOBACTERIUM TUBERCULOSIS INFECTION

tion. The immunosuppressive drugs were prednisolone (in all patients) with cyclosporine (n ⫽ 9) or tacrolimus (n ⫽ 1) and azathioprine (n ⫽ 9 or mycophenolate mofetil (n ⫽ 1). All patients with posttransplant TB were treated with isoniazid, rifampicin, ethambutol, and pyrazinamide or morfazinamide. Only one patient developed isoniazid-related hepatotoxicity, but after tapering the isoniazid dose, the hepatic transaminase levels returned to normal. No allograft rejection occurred during anti-TB therapy. Eight patients successfully responded to therapy, other two patients (20%) died due to dissemination of disease. They were both in the first year after transplantation and both had pulmonary involvement. DISCUSSION

TB is a serious infection associated with a high risk of mortality after renal transplantation. Due to improved living conditions, TB incidence is lower in industrialized countries than in developing countries. The annual case rate in the United States3 was 5.1 per 100,000, while it was 168 per 100,000 in India.4 The epidemiological risk in a country determines the risk of developing TB after transplantation. Similar to the general population the reported incidence of posttransplant TB was lower in United States5 (0.45%) than in India6 (12% to 20%). The incidence of TB in Turkey7 was about 26.2 per 100,000 population; in our study the incidence of posttransplant TB was 3.5%. The higher incidence in our study than in United States was probably associated with the moderately high frequency of TB in Turkey. The most common presentation of TB in the general population is pleuropulmonary involvement, but extrapulmonary involvement is more common in renal transplant recipients.8 In our study, 50% of patients developed extrapulmonary TB. Because of the immunosuppression and atypical presentation of extrapulmonary TB, the diagnosis of TB is often delayed, frequently being complicated in renal allograft recipients. We previously described TB otitis media in a renal allograft recipient, which was complicated with a postauricular fistula after using several courses of empiric antibiotics for the treatment of recurrent chronic otitis media.9 The immunosuppressive medications to prevent organ rejection are the most important factors predisposing to the

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development of TB after transplantation. The relation between cyclosporine therapy and early posttransplant TB has been previously described. It was suggested to be associated with the depressing effect of cyclosporine on lymphocyte proliferation and macrophage function.6 Although, nine patients were on cyclosporine therapy in our study, the incidence of TB in the first year after transplantation was not high (1%). It has been demonstrated that rifampin leads to increased cyclosporine metabolism due to cytochrome P450 induction. This may cause an acute rejection episode due to the decreased blood levels of cyclosporine.10 However, no acute allograft rejection occurred among our patients during rifampin treatment. In conclusion, the diagnosis of posttransplant TB is often difficult and associated with a high risk of mortality. The physicians should be aware of the atypical presentations of the extrapulmonary disease among renal transplantation patients.

REFERENCES 1. Niewczas M, Ziolkowski J, Rancewicz Z, et al: Tuberculosis in patients after renal transplantation remains still a clinical problem. Transplant Proc 34:677, 2002 2. Dridi A, Kaaroud H, Boubaker K, et al: Tuberculosis in renal transplant recipients. Transplant Proc 35:2682, 2003 3. Centers for Disease Control and Prevention (CDC): Trends in tuberculosis—United States, 1998 –2003. MMWR Morb Mortal Wkly Rep 19:209, 2004 4. Maher D, Raviglione M: Global epidemiology of tuberculosis. Clin Chest Med 26:167, 2005 5. Jie T, Matas AJ, Gillingham KJ, et al: Mycobacterial infections after kidney transplant. Transplant Proc 37:937, 2005 6. John GT, Shankar V, Abraham AM, et al: Risk factors for posttransplant tuberculosis. Kidney Int 60:1148, 2001 7. Zozio T, Allix C, Gunal S, et al: Genotyping of Mycobacterium tuberculosis clinical isolates in two cities of Turkey: description of a new family of genotypes that is phylogeographically specific for Asia Minor. BMC Microbiol 26:44, 2005 8. Queipo JA, Broseta E, Santos M, et al: Mycobacterial infection in a series of 1261 renal transplant recipients. Clin Microbiol Infect 9:518, 2003 9. Ergun I, Keven K, Sengul S, et al: Tuberculous otitis media in a renal transplant recipient. Am J Kidney Dis 43:e1, 2004 10. Klote MM, Agodoa LY, Abbott K: Mycobacterium tuberculosis infection incidence in hospitalized renal transplant patients in the United States, 1998 –2000. Am J Transplant 4:1523, 2004