Tuberculosis is one of the leading infections after renal transplant, particularly in developing countries where the incidence and prevalence in the general population are high. Diagnosis requires bacteriologic and histologic confirmation. Interactions among the antitubercular drugs and the immunosuppressive agents have to be considered while prescribing, and surveillance for adverse effects is required. Although rare, case reports are available on extrapulmonary tuberculosis in allograft recipients. Here, we present a 25-year-old kidney transplant recipient who was diagnosed with lymph node tuberculosis under uncommon circumstances but who had a good outcome. This case report illustrates the difficulties in diagnosis of tuberculosis, changes in therapeutic protocols, and prognostic factors and highlights the effects of infectious complications with immunosuppressive therapy in this particular patient population.
Key words : Immunocompromised host, Kidney transplant, Lymph nodes, Mycobacterium infections
Tuberculosis (TB) is a common opportunistic infection in renal transplant patients, with high prevalence in developing countries and having an estimated frequency in transplant patients of 20 to 74 times greater than the general population.1 In some reports, the prevalence of TB after kidney transplant has ranged from 0.5% to 15%.1 In our transplant unit, between 1986 and 2013, the prevalence of TB was estimated at 3.2% among 491 renal transplant recipients.2 Tuberculosis causes significant morbidity that imposes significant economic burden on patients and healthcare agencies. Pyrexia of unknown origin is a common clinical presentation. Laboratory culture and sensitivity tests are required for all cases. In this report, we present a patient treated at our center and review the existing knowledge on TB after renal transplant, the difficulties in diagnosis, treatment modalities in this particular population, prognosis, and risk factors.
We present a 25-year-old Tunisian male patient who had been seen at our nephrology department since 2002 for renal failure attributed to a vesicoureteral reflux secondary to posterior urethral valve. This condition had been discovered at age of 7 months and had required multiple urologic surgeries, the latest being right ureteronephrectomy. In December 2008, he had a preemptive renal transplant from a living related donor (his father) with 3 HLA matches. The postoperative course was uneventful. As induction therapy, he received antilymphocyte serum for 7 days, methylprednisolone, and mycophenolate mofetil (MMF). The patient was maintained on prednisone at 10 mg/day, mycophenolate mofetil at 500 mg twice per day, and tacrolimus at 4 mg twice per day and showed adequate renal function.
In May 2011, the patient was hospitalized with fever, asthenia, abdominal pain, and myalgia. Physical examination on admission revealed an asthenic patient, with fever up to 40°C, blood pressure of 100/50 mm Hg, and pulse rate of 96 beats/min. The patient indicated graft pain on palpitation. There were no peripheral lymph nodes or hepatosplenomegaly. Laboratory investigations revealed white blood cell count of 17 410/mm3, platelet count of 186 000/mm3, hematocrit level of 32%, serum urea nitrogen level of 16 mmol/L, elevated serum creatinine level of 147μmol/L, and elevated C reactive protein serum level of 166 mg/L. The erythrocyte sedimentation rate was 120 mm/h. Liver function tests, lipid profile, and chest radiography were normal. Abdominal computed tomography scan revealed an appendiceal abscess measuring 44 × 28 mm associated with several adenomegalies, with a large iliac adenomegaly measuring 11.5 cm (Figure 1). The patient underwent an appendectomy (the appendix was plagued) and drainage of the abscess. Antibiotic therapy included cefotaxime, metronidazole, and amikacin. Despite the treatment course, he remained febrile. Abdominal echography showed intra-abdominal fluid collection (Figure 2). A second computed tomography scan revealed necrotic mesenteric lymphadenopathy and intra-abdominal fluid collection (Figure 3).
When we considered the radiologic findings of the patient and the fact that our country is endemic for TB, our diagnosis was directed toward tuberculosis of the lymph node, despite negative TB skin test. Tests for Mycobacterium tuberculosis by sputum and urine specimens were negative. Bacteriologic examination of the drainage liquid isolated Escherichia coli and showed the presence of Mycobacterium tuberculosis. The patient underwent surgical drainage of lymph nodes. In vitro studies showed the organisms to be fully susceptible to all antituberculosis drugs. Four drugs (isoniazid, rifampin, ethambutol, and pyrazinamide) were administered orally along with the usual doses of ciprofloxacin and piperacillin sodium/tazobactam sodium. The dose of corticosteroids was increased and that of tacrolimus was adjusted to the recommended therapeutic range. Patient outcome with antitubercular therapy has so far been favorable, with prolonged apyrexia and regression of the pulmonary abnormalities. This regimen, maintained over 18 months, was well tolerated without any modification in liver tests and graft function and complete regression of lymphadenopathy and abdominal fluid collections shown with computed tomography scan. At 5-year follow-up, the patient was still doing well after TB infection.
Kidney transplant recipients are at a higher risk of developing TB than the general population.2,3 Tuberculosis generally occurs in the first year of renal transplant.4-6 However, our patient was diagnosed with TB at 5 years after renal transplant. The mode of contamination was probably a reactivation of latent infection.7 The use of immunosuppressive drugs and corticosteroids decreased the host resistance to infection by interfering with T-cell-mediated function.8 Recipients who receive grafts from deceased donors and preoperative evidence of latent TB are 2 major risk factors for developing TB in kidney transplant recipients.9 A previous history of infection, long duration of dialysis before transplant, and poor socioeconomic conditions are also considered as risk factors.10 In our case, we did not identify any of the risk factors reported in the literature.
The clinical presentation of TB may be unusual in renal transplant recipients.4 Pulmonary symptoms are sometimes atypical and may include an unusual gastrointestinal symptomatology11-13 as in our patient. In kidney recipients with prolonged fever with unusual clinical manifestations, TB should be considered, especially in endemic countries.2,4,10
The bacteriologic evidence of Mycobacterium tuberculosis infection is difficult. The TB skin tests and culture are often negative in the transplant population.14,15 As shown in our patient, traditional tests such as Ziehl-Neelsen staining and culture of sputum specimens for revealing Mycobacterium tuberculosis were negative. Therefore, multiple tissue specimens obtained from lymph nodes, bone marrow specimens, liver, kidney, and pleural and peritoneal samples, according to the clinical context, may be necessary. High-resolution computerized tomography, which may show characteristic lesions, may help in an improved ability to diagnose.16 In addition, histopathologic proof, whenever possible, may also improve obtaining a diagnosis. Any histopathologic tissue with evidence of granuloma should be suspected to be due to tuberculosis unless proven otherwise.17 Interferon-gamma detection is a diagnostic test developed recently to improve sensitivity, which allows a rapid TB diagnosis, particularly in patients with culture-negative TB.14 However, it should not be used initially for diagnosis of active TB.
In transplant patients, TB is a major therapeutic problem. Both treatment delay and toxicity from TB care are responsible for many clinical complications and for high mortality in this population.18-20 Some authors have reported an increased rate of acute rejection and a higher rate of graft loss because of interactions between corticosteroids and rifampicin.4,9 Rifampicin, a vital drug in antitubercular therapy, induces the cytochrome P450 microsomal enzyme system, which is responsible for metabolizing cyclosporine, sirolimus, and prednisolone. An adequate and regular monitoring of immunosuppressive drugs avoids the risk of rejection. Acute rejection has been observed in 18% to 29% of patients in the literature.21 It can be seen even after antitubercular therapy was discontinued.15 Blood levels of calcineurin inhibitors should be monitored closely with an increase in doses.21,22 Antilymphocyte globulin can be used as antirejection prophylaxis.15 Chronic allograft nephropathy has been reported in 65% of patients, which has a negative impact on graft survival.23 However, a favorable renal outcome was observed in our patient.
The mortality in renal transplant patients with TB varies from 14.3% to 31.9%. It is mostly related to the severity of TB and the complications of anti-TB therapy.24,25 Mortality is higher when TB occurs during the first year after kidney transplant, among poor-nourished patients, those treated with steroids, and those with hypoxia.26
Tuberculosis after renal transplant is a common problem, particularly in developing countries where the incidence and prevalence in the general population is high. A high index of suspicion is important in diagnosing the problem. The interactions between anti-TB drugs and immunosuppressive agents should be considered, and adverse effects should be monitored.
Volume : 15
Issue : 1
Pages : 200 - 203
DOI : 10.6002/ect.mesot2016.P79
From the Nephrology Department, Laboratory of Renal Pathology and Laboratory of
Kidney Transplantation Immunology and Immunopathology, Charles Nicolle Hospital,
Acknowledgements: The authors declare that they have no sources of funding for this study, and they have no conflicts of interest to declare.
Corresponding author: Meriam Hajji, Nephrology Department, Laboratory of Renal Pathology and Laboratory of Kidney Transplantation Immunology and Immunopathology, Charles Nicolle Hospital, Tunis, Tunisia
Phone/Fax: +216 21578 566
Figure 1. High Cecum Located With Side-To-Cecal Appendix Measuring 9.3 mm in Contact With Liquid Formation, Measuring 44 × 28mm, Enhanced After Contrast Injection and With Right Iliac Adenomegaly at Most Voluminous Measuring 11.5 mm
Figure 2. Presence of a New Intra-abdominal Fluid Near the Upper Pole of the Graft
Figure 3. Computed Tomography Scan After Appendectomy, Flattening of Appendiceal Abscess, and Drainage Blade