Renal Allograft Tuberculosis with Infected Lymphocele Transmitted from the Donor

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Case Report

Maryam Ali Al-Nesf1, Omar Isam Al-Ani2, Ahmed Abdul-Rahman Al-Ani1, Awad Hamed Rashed1

Departments of 1Medicine and 2Surgery, Hamad General Hospital, Doha, Qatar

ABSTRACT. Transmission of tuberculosis (TB) from a donor through renal transplantation is a rare incident. We are reporting a 53-year-old Qatari woman diagnosed with renal allograft TB infection. The disease was confirmed by isolation of Mycobacterium tuberculosis from fluid from the lymphocele and demonstration of caseating granuloma in graft biopsy with acid-fast bacilli seen on Ziehl–Neelsen staining. The diagnosis was made quite early post-transplantation. The presence of the granuloma, which is unusual with patients on intensive immunosuppressant medications, suggests that transmission of the infection occurred from the donor rather than from the activation of latent infection. In reviewing the literature, we found ten case reports of TB in transplanted kidney with transmission of TB infection from the donor. The presence of TB in lymphocele in association with the infected transplant by TB, to the best of our knowledge, was reported only once in the literature. Our case had unfavorable outcome and ended by renal allograft nephrectomy and hemodialysis. We are presenting this case of TB infection of renal allograft and lymphocele diagnosed early post-transplantation transmitted from the donor and perti- nent review from the literature.

Introduction dence differs in the literature from region to region, accounting for as high as 5.7–11.8 % in Tuberculosis (TB) is one of the most com- India and less than 1% in the United States.1,2 It mon opportunistic infections developing follo- carries a high mortality and morbidity rate in wing renal transplantation. The incidence of addition to graft dysfunction and loss among TB among organ recipients is as much as 74- renal transplant recipients.2 times that of the general population.1 The inci- Mycobacterium tuberculosis can be transmit- Correspondence to: ted by transplantation (Table 1). It was estimated previously to account for 4% of the repor- Dr. Maryam Ali Al-Nesf, ted post-transplant TB cases.1 The presence of Department of Medicine, TB-infected lymphocele or para-nephric ab- Hamad Medical Corporation, scess along with the transplanted kidney is a P. O. Box 3050, Doha, Qatar rare occurrence, and, to the best of our know- E-mail: [email protected] ledge, was reported only once before.3 [Downloaded free from http://www.sjkdt.org on Friday, April 04, 2014, IP: 202.241.78.236] || Click here to download free Android application for this journal

Renal allograft tuberculosis with infected lymphocele 371

prior to transplantation. No isoniazid (INH) prophylaxis was given. She was maintained on multiple immunosuppressant drugs including mycophenolate mofetil, cyclosporine and pred- nisolone. Physical examination showed a febrile patient (38.2°C) with stable hemodynamic status. There was no lymphadenopathy or rash. Retina examination showed no evidence of choroidal TB. Abdominal examination revealed left side palpable allograft kidney. Other systemic exa- minations were unremarkable. The initial investigations showed hemoglobin 6.9 g/dL, total leukocyte count 2100/mm3, polymorphs 38.6%, lymphocytes 48% and platelets 125,000/µL. The erythrocyte sedi- Figure 1. Renal allograft biopsy showing acid- mentation rate was 102 mm in the first hour. fast bacilli was stained positive (modified Ziehl– Urine examination was negative and no acid- Neelsen stain) seen in granuloma (arrow). fast bacilli (AFB) was seen in Ziehl–Neelsen (Z-N) staining. Serum urea was 15.5 mmol/L, Case Report creatinine was 128 µmol/L and calcium was 2.17 mmol/L. Blood and urine cultures done A 53-year-old Qatari female patient with this time were sterile. Chest X-ray and com- chronic kidney disease secondary to long-stan- puted tomography (CT) scan of the chest were ding diabetes mellitus (DM) and hypertension, normal. Ultrasound, CT scan and magnetic had two live unrelated renal allograft trans- resonance imaging of the abdomen showed a plants. The first transplant was performed in large lymphocele surrounding the transplant, 1993. She sustained chronic allograft rejec- with normal angiographic appearance of pelvic tion and ended up in transplant failure in early veins and arteries, atrophic native and normal- 2000. The second renal transplant was per- appearing renal graft. There was no evidence formed in November 2005. The transplantation of TB at any site. Transplant renogram showed was carried out in a different center (in normal perfusion with normal parenchymal Philippines) with a haplo-matched donor. Fur- appearance. ther detailed information about the donor was Repeated gram staining and cultures of lym- not available. It was followed by multiple phocele fluid were negative. However, lym- complications, including dehiscence of the phocele fluid was reported positive for AFB transplant wound with a sinus having persis- staining and the culture grew Mycobacterium tent discharge from lymphocele. She deve- tuberculosis. The second transplant kidney loped allograft dysfunction; the initial one was biopsy showed tubulo-interstitial inflammation secondary to cyclosporine toxicity proven by with non-caseating granulomas with AFB seen the allograft biopsy in December 2005. on Z-N staining. There was no evidence of She was re-admitted in January 2006 with concomitant fungal infections (Figure 1). rising urea and creatinine. She was complai- The patient was started on full-dose qua- ning of abdominal pain and low-grade fever. druple anti-tubercular therapy (rifampicin, iso- Escherichia coli wound infection was found niazide, ethambutol and pyrazinamide). Despite and was treated initially, but the patient conti- the early diagnosis and treatment, the patient nued to be febrile. There was no past history of continued to have deterioration of the kidney TB in the patient or in her family. Purified function associated with symptomatic volume protein derivative (PPD) skin test was negative overload requiring hemodialysis. Because of [Downloaded free from http://www.sjkdt.org on Friday, April 04, 2014, IP: 202.241.78.236] || Click here to download free Android application for this journal

372 Al-Nesf MA, Al-Ani OI, Al-Ani AA, et al

persistent fever despite anti-tubercular and false-negative tests among chronic renal fai- empirical antifungal therapy, although with no lure patients,4 it is being advised now by apparent focus of fungal infection, transplant others.6,7 INH hepatotoxicity may not be as nephrectomy was performed. Histopathology high as previously thought, especially in non- of the removed graft was positive for fungal hepatic transplant recipients.1 hyphae and spores; however, no culture was The diagnosis of TB is often made retros- performed. After nephrectomy, the patient res- pectively after observing a complete response ponded well to treatment. She was continued to anti-TB therapy. The most common site for on anti-tubercular therapy for a total of one TB is pleuro-pulmonary in renal transplant pa- year. She is currently maintained on regular tients, accounting for 28–50%, followed by hemodialysis without evidence of tuberculosis disseminated TB. Patients presenting with reactivation. pyrexia of undetermined etiology account for 20–40%.4 Examination of the retina is impor- Discussion tant to differentiate disseminated TB from isolated graft infection.9 The other method is by TB is more frequent in renal transplant re- bone marrow examination, which is not rou- cipients than in the general population in tro- tinely done. pics.2,4 In developed countries, the disease The time to TB diagnosis from transplanta- represents a significant health problem in tion date in renal allograft recipients varies. On patients following renal transplantation.1 It an average, it usually occurs more than two causes serious damage to the graft and may years following transplantation. It was estima- lead to graft loss either because of delayed ted to occur 11 months following transplan- diagnosis or due to renal allograft rejection tation by some studies.1,10 that can be attributed to the reduction in effi- A search of the literature by us revealed that ciency of the immunosuppressant drugs.4,5 transmission of TB from the donor along with The risk factors of TB post-renal transplan- the transplanted kidney was reported only in tation are highly influenced by disease ende- ten patients in previous case reports and case micity and the immunosuppressant regimen series. Characteristics of those patients in com- used following transplantation.6 parison with our case are summarized in Table Early tuberculosis infection (within the first 1. Previously, it was estimated to account for year) post-transplantation was associated with 4% of the reported post-transplant TB cases.1 the use of cyclosporine therapy.6,7 Other risk Occurrence of TB in renal allograft with factors for post-transplantation TB were DM infected lymphocele or para-nephric abscess is and chronic liver diseases (CLDs). The combi- reported in only one previous case report.3 In nation of both DM and CLD and pre- or post- this case report, transmission from donor was transplantation TB, along with other co-exis- not suggested and it was diagnosed five months ting infections, are important risk factors for post-transplantation by both ultrasound-guided death.7 The risk of post-transplant TB is in- aspirate from peri-nephric collection and urine creased in relation to prolonged duration of being tested positive for AFB. Our patient did pre-transplant hemodialysis and the number of not have any of the recognized risk factors for post-transplant rejection episodes.6,8 The fre- TB, including previous exposure, malnutrition quency of TB has been also correlated with a or living in an endemic area. The incidence of maintenance steroid dose of more than 10 all forms of TB in Qatar was 55/100,000 popu- mg/day or the use of pulse steroid therapy.6 lation in 2008.11 The routine use of INH prophylaxis is contro- Our case report is unique in providing diag- versial in endemic areas. While earlier it was nosis of the TB from the lymphocele discharge not recommended by some, because of the as usually the infection is checked in the urine high degree of PPD skin test positivity in the sample and in the allograft biopsy where gra- general population and the high frequency of nulomas with AFB-positive bacilli are found.12-18 [Downloaded free from http://www.sjkdt.org on Friday, April 04, 2014, IP: 202.241.78.236] || Click here to download free Android application for this journal Renal allograft tuberculosis with infected lymphocele infected with tuberculosis allograft Renal

Table 1. Tuberculosis isolated to renal allograft transmitted from donor with or without dissemination of tuberculosis by case reports and case series. Time from Case No. of transplantation Tuberculosis Type of transplant Diagnosis methods Outcome report patients to TB diagnosis dissemination no. (months) Graft biopsy showing caseating Deceased donor renal 1 29 No granuloma and urine culture grows Recovery 15 transplant AFB. Graft showing caseating granuloma, Deceased donor renal with AFB seen on Z-N staining. Failure with allograft 1 3 No 8 transplant Positive early morning urine cultures nephrectomy for MTB. Deceased donor renal Both urine grows AFB, both 2 2, 6 Yes, both 13 transplant (same donor) disseminated TB. First: Bone marrow aspirate positive for AFB. Former expired, Deceased donor renal 2 1.5, 1.5 Yes, both Second: Blood and urine AFB, bone second patient reco- 12 transplant (same donor) marrow granuloma and PCR posi- very tive. No available 1 - Yes - - 9 information First: Bone marrow, urine and pleural Failure with allograft Deceased donor renal First: Yes, 2 1, 1 fluid positive for AFB. Second: nephrectomy (both) 10 transplant (same donor) Second: No Urine positive for AFB. Graft biopsy showing caseating Deceased donor renal granuloma, with AFB seen on Z-N Failure with allograft 1 14 No 14 transplant staining + positive early morning nephrectomy urine cultures for MTB. Graft biopsy showing caseating Failure with allograft Living unrelated renal Our 1 2 No granuloma, with AFB seen on Z-N nephrectomy transplant case staining. Lymphocele.

Z-N stain: Ziehl–Neelsen stain, MTB: Mycobacterium tuberculosis, AFB: Acid-fast bacilli 37 3 [Downloaded free from http://www.sjkdt.org on Friday, April 04, 2014, IP: 202.241.78.236] || Click here to download free Android application for this journal

374 Al-Nesf MA, Al-Ani OI, Al-Ani AA, et al

Moreover, our case was unusual compared with the same donor should be checked as well. previously reported cases as the transmission occurred from a live unrelated transplant rather Conflict of Interest than a deceased donor transplant (Table 1). Finding a granuloma formation in the early The authors of this manuscript have no con- course post-transplantation supports the high flicts of interest to disclose as described by the possibility of transmission of the infection Saudi Journal of Kidney Diseases and Trans- from the donor kidney rather than activation of plantation. Also, this manuscript was not pre- latent infection in the host. It was assumed pared or funded by any commercial organi- earlier that a high dose of corticosteroids plays zation. an important role in the presentation of an exudative form of TB, preventing the forma- References tion of granulomas, and granulomatous forms occur mainly after the first year of trans- 1. Singh N, Paterson DL. Mycobacterium tuber- plantation.5 culosis infection in solid-organ transplant reci- The initial renal graft biopsy was negative for pients: Impact and implications for manage- presence of granulomatosis disease. We be- ment. Clin Infect Dis 1998;27:1266-77. lieve that the reason for that is related to the 2. Sakhuja V, Jha V, Varma PP, Joshi K, Chugh KS. The high incidence of tuberculosis among nature of granulomatosis that was scattered renal transplant recipients in India. Transplan- throughout and not involving the whole organ. tation 1996;61:211-5. Possibly, the first biopsy missed an area with 3. Wong TY, Szeto CC, Ho KK, Leung CB, Li granulomas. Also, it is important to mention PK. Successful medical eradication of tuber- that superinfection with E. coli masked the culosis paranephric abscess in renal trans- presentation. Moreover, the fungal infection plantation. Nephrol Dial Transplant 1999;14: that involved the transplanted kidney was not 1288-90. present at the beginning and it was not shown 4. Jha V, Chugh S, Chugh KS. Infections in dia- in either biopsy taken earlier. The immuno- lysis and transplant patients in tropical coun- suppression was stopped with nephrectomy tries. Kidney Int 2000;57:S85-93. 5. Biz E, Pereira CA, Moura LA, et al. The use of performed in order to gain control of the infec- cyclosporine modifies the clinical and histo- tion. These are common problems with this pathological presentation of tuberculosis after type of patient. renal transplantation. Rev Inst Med Trop Sao Transmission of TB from the donor should be Paulo 2000;42:225-30. suspected when there is absence of clear risk 6. John GT, Shankar V, Abraham AM, Mukundan factors or other evidence from recipient pre- U, Thomas PP, Jacob CK. Risk factors for transplantation screening.16 Other recipients post-transplant tuberculosis. Kidney Int 2001; from a common donor might be at risk and 60:1148-53. should be evaluated for TB as well.9,14,16,17 7. John GT. Infections after renal transplantation TB of the renal allograft should be seriously in India. Indian J Nephrol 2003;13:14-9. 8. Basiri A, Moghaddam SM, Simforoosh N, et considered in any transplant patient with pyre- al. Preliminary report of a nationwide case- xia of unknown origin. Renal allograft biopsy control study for identifying risk factors of should be performed as early as possible for tuberculosis following renal transplantation. every transplant case where a cause for fever is Transplant Proc 2005;37:3041-4. not reached. 9. Mansour AM. Renal allograft tuberculosis. Because it often goes unsuspected, a high Tubercle 1990;71:147-8. index of suspicion is needed to diagnose it 10. Naqvi R, Akhtar S, Noor H, et al. Efficacy of timely in order to avoid graft loss. TB transmit- isoniazid prophylaxis in renal allograft reci- ted with the organ donor should be thought of pients. Transplant Proc 2006;38:2057-8. if the donor status is unknown or if the donor 11. TB Unit of the WHO Regional Office for Eastern-Mediterranean Region: Country profile is from endemic areas. Other recipients from [Downloaded free from http://www.sjkdt.org on Friday, April 04, 2014, IP: 202.241.78.236] || Click here to download free Android application for this journal

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2008-2009: QATAR. Oklahoma and Texas, 2007. MMWR Morb 12. Siu YP, Tong MK, Leung KT, Yung CY. Mortal Wkly Rep. 2008;57:333-6. Successful kidney re-transplantation in a 16. Mourad G, Soulillou JP, Chong G, Pouliquen patient with previous allograft kidney tuber- M, Hourman M, Mion C. Transmission of culosis. Transpl Infect Dis 2004;6:132-5. Mycobacterium tuberculosis with Renal Allo- 13. Qunibi WY, al-Sibai MB, Taher S, et al. grafts. Nephron 1985;43:82-5. Mycobacterial infection after renal transplan- 17. Graham JC, Kearns AM, Magee JG, et al. tation-report of 14 cases and review of the Tuberculosis transmitted through transplan- literature. Q J Med 1990;77:1039-60. tation. J Infect 2001;43:251-4. 14. Peters TG, Reiter CG, Boswell RL. Trans- 18. Malone A, McConkey S, Dorman A, Lavin P, mission of tuberculosis by kidney transplan- Gopthanian D, Conlon P. Mycobacterium tation. Transplantation 1984;38:514-6. tuberculosis in a renal transplant transmitted 15. Transplantation-Transmitted Tuberculosis - from the donor. Ir J Med Sci 2007;176:233-5.