Tuberculosis In Kidney Transplant Recipients Research Articles

Diagnostic and therapeutic challenges of tuberculosis in kidney transplant recipients; a case series study

Diagnostic and therapeutic challenges of tuberculosis in kidney transplant recipients; a case series study

Radiological presentation of active pulmonary tuberculosis in kidney transplant recipients: a retrospective study of four cases and a review of the literature.

Although kidney transplantation is the best therapeutic option for patients with chronic kidney disease, the immunosuppression required greatly increases susceptibility to infections that are responsible for high post-transplant mortality. Pulmonary tuberculosis (TB) represents a major cause of such infections, and its early diagnosis is therefore quite important. In view of that, we researched the manifestations of active pulmonary TB in kidney transplant recipients, through chest X-ray and computed tomography (CT), as well as determining the number of cases of active pulmonary TB occurring over a 3.5-year period at our institution. We identified four cases of active pulmonary TB in kidney transplant recipients. The CT scans provided information complementary to the chest X-ray findings in all four of those cases. We compared our CT findings with those reported in the literature. We analyzed our experience in conjunction with an extensive review of the literature that was nevertheless limited because few studies have been carried out in lowand middle-income countries, where the incidence of TB is higher.

Tuberculosis in Kidney Transplant Recipients: A Nationwide Cohort in a Low Tuberculosis Incidence Country.

World Health Organization recommends tuberculosis (TB) preventive treatment for risk groups such as patients preparing for organ transplantation. Pretransplant screening or treatment of latent TB infection has not been routine practice in Finland. In this nationwide registry study, we assessed the risk of TB among kidney transplant recipients compared to the general population. TB cases were identified by data linkage of the national infectious disease and the national transplant registries between 1995 and 2019. Standardized incidence ratios were calculated with adjustment for age, sex, and annual TB dynamics. A total of 4101 kidney transplants in 3900 recipients with a follow-up of 37 652 patient-years were included. Eighteen TB cases were detected. Patients diagnosed with TB were older (median age 64 y, interquartile range 56-66) at transplantation than those without TB (median 51 y, interquartile range 41-60, P < 0.001). The standardized incidence ratio of TB was 6.9 among kidney transplant recipients compared to general population during the whole study period 1995-2019 but decreased from 12.5 in 1995-2007 to 3.2 in 2008-2019. The standardized incidence ratio was 44.2 during the first year after transplantation. Significant differences in 5-y graft losses were not detected between TB patients and those without TB. The standardized incidence ratio of TB in kidney transplant recipients has decreased over the years, but these patients remain at risk of TB, especially during the first posttransplant year. Cost-benefit analysis is required to address feasibility of latent TB infection screening among transplant candidates in countries with low incidence of TB.

Mycobacterium Tuberculosis Infection after Kidney Transplantation: A Comprehensive Review.

Tuberculosis (TB) in kidney transplant (KT) recipients is an important opportunistic infection with higher incidence and prevalence than in the general population and is associated with important morbidity and mortality. We performed an extensive literature review of articles published between 1 January 2000 and 15 June 2022 to provide an evidence-based review of epidemiology, pathogenesis, diagnosis, treatment and outcomes of TB in KT recipients. We included all studies which reported epidemiological and/or outcome data regarding active TB in KT, and we approached the diagnostic and treatment challenges according to the current guidelines. Prevalence of active TB in KT recipients ranges between 0.3–15.2%. KT recipients with active TB could have a rejection rate up to 55.6%, a rate of graft loss that varies from 2.2% to 66.6% and a mortality rate up to 60%. Understanding the epidemiological risk, risk factors, transmission modalities, diagnosis and treatment challenges is critical for clinicians in providing an appropriate management for KT with TB. Among diagnostic challenges, which are at the same time associated with delay in management, the following should be considered: atypical clinical presentation, association with co-infections, decreased predictive values of screening tests, diverse radiological aspects and particular diagnostic methods. Regarding treatment challenges in KT recipients with TB, drug interactions, drug toxicities and therapeutical adherence must be considered.

Tuberculosis in kidney transplant recipients: A retrospective study from a tertiary care center - An observational study

Background: The incidence of tuberculosis (TB) among transplant recipients varies from 5% to 15% across the globe. We conducted a retrospective study to identify the incidence of TB among kidney transplant recipients in our transplant unit. Materials and Methods: We assessed the patients who underwent kidney transplantation in our transplant unit during the study period from January 2014 to June 2018 and included those recipients who had bacteriologically confirmed TB. We excluded the patients who had TB before transplant and those recipients who were initiated on antituberculosis treatment (ATT) empirically. The details collected were: 1. Clinical data, the presenting symptoms, and clinical findings. 2. Diagnostic investigation: Microbiological/histopathological/radiological/bronchoalveolar lavage/fluid (pleural/peritoneal/cerebrospinal fluid) analysis. 3. Antituberculous regimen, dose, and duration of the therapy. 4. Relapse/patient and graft outcome after treatment.Results: The total number of patients who underwent kidney transplantation during the study period was 177. TB occurred in 21 patients after transplantation. The incidence of TB in our transplant unit was 11.86%. In these 21 recipients, 8 had pulmonary TB and the remaining 13 had extrapulmonary/disseminated TB, which included two patients with disseminated TB and one patient with allograft dysfunction with thrombotic microangiopathy which was attributed to TB as it responded to first-line antituberculous drugs. The mortality rate was 23.8%, as five patients expired. After excluding patients who expired, the graft survival at 1 year after ATT completion was 90.5%. Conclusion: For most developing nations, the World Health Organization's “End TB Strategy” remains far from their dream. An ideal investigation to detect TB in its early stage is essential in posttransplant recipients to reduce the morbidity and mortality associated with it.

Risk factors and clinical outcomes of tuberculosis among kidney transplant recipients in high endemic country.

Tuberculosis (TB) is considered as a challenge issue in solid organ transplant recipients because of high morbidity and mortality. Active TB after transplant mostly occurs from reactivation of latent infection. Understanding risk factors and clinical information of TB may provide an appropriate prevention and treatment strategies in this specific patient population, however data from high endemic area is scarce. A matched single-center, case-control study was conducted in our institute. Cases were defined as newly diagnosed confirmed or clinical active TB in patients who underwent kidney transplant (KT) between April 1992 and October 2018. For each case, 5 controls were matched by age and sex. Risk factor associated with TB was determined using univariate and multivariate conditional logistic regression. Between study period, KT was performed in 787 patients. Twenty-seven patients (3.43%) were diagnosed with active TB including 20 confirmed and 7 clinical diagnosed cases. The global incidence of TB in our population was 315 cases per 100000 patients per year. Among 27 cases, pulmonary involvement was the most common (48.1%) followed by disseminated (18.5%), extrapulmonary (14.8%), pleura (11.1%) and pleuropulmonary (7.4%) TB. Allograft rejection was significantly associated with active TB (P<.001). The median onset duration of infection was 17months (IQR, 4-59months) after KT. Twenty-four (88.9%) patients received rifampicin containing regimen for treatment with median duration of 10months (IQR, 6-12months). All patients were cured after complete treatment, however those with TB remained having unfavorable outcomes including higher all-cause mortality and graft loss. Incidence rate of TB in KT recipients is higher than normal population. Allograft rejection was identified as a significant risk factor. Increase unfavorable outcomes including graft loss and mortality were also observed among patients with TB.

The usefulness of quantitative interferon-gamma releasing assay response for predicting active tuberculosis in kidney transplant recipients: A quasi-experimental study

ObjectivesWe evaluated the effectiveness of IGRA-based isoniazid (INH) treatment with the diagnostic value of quantitative IGRA titer for post-transplant tuberculosis (TB) in kidney transplant (KT) recipients. MethodsAll adult KT recipients were enrolled from January 2014 to December 2017. The development of TB after KT was observed, stratified by quantitative IGRA results as well as by IGRA results with/without INH treatment. ResultsOf 1150 KT recipients, 322 (28%) revealed positive IGRA results (≥0.35 IU/mL) and 12 (1.0%) developed TB. Seven (3.2%) of 217 patients with positive IGRA without INH developed TB, whereas none of 105 patients with positive IGRA with INH developed TB (rate difference −1616 per 100,000 person-years, P = 0.016) and 5 (0.6%) of 828 patients with negative or indeterminate IGRA developed TB (rate difference −1388 per 100,000 person-years, P<0.001). Among the 217 positive IGRA patients without INH, 6 (6.4%) of 94 patients who had positive IGRA titer>2.96 IU/mL developed TB, whereas one (0.8%) of 123 patients who had positive IGRA titer≤2.96 IU/mL developed TB (rate difference 2964 per 100,000 person-years, P = 0.017). ConclusionsIGRA-based INH treatment with risk stratification by quantitative IGRA results appears to be effective to prevent the development of TB in KT recipients.

Pulmonary and intestinal tuberculosis in a kidney transplant recipient

Introduction. Tuberculosis is one of the most common infections in the general population, as well as among the recipients of solid organs. In kidney transplant recipients, the diagnosis of tuberculosis is often extremely difficult to make because of unclear clinical and radiological symptoms, and a highly frequent atypical (extrapulmonary) localization. The tuberculosis treatment in patients on drug immunosuppression is a significant problem.Clinical case. At five years after renal transplantation, the patient noted the onset of fever up to 38 degrees C. It was suspicious of respiratory infection. Chest X-ray, computed tomography, and ultrasound examination of the graft revealed no pathology. Antibacterial and antiviral therapy brought stable improvement. A repeated computer tomography demonstrated an enhanced pulmonary pattern in S6 of the left lung with visualization of small grouped lesions located peribronchially, the terminal ileitis in the abdominal cavity: (an intensive contrast accumulation in the mucosa of the affected part of the small intestine, the mesentery hypervascularity at this level). A colonoenteroscopy with a ileum intestine biopsy was performed; the findings were highly consistent with a tuberculous process. A targeted treatment of tuberculosis was carried out, which had a marked positive trend.Conclusion. Thus, the diagnosis of tuberculosis in kidney transplant recipients is complex; the clinical signs and instrumental test results are often ambiguous, which greatly complicates the timely diagnosis. An integrated approach with the use of modern diagnostic methods is required.

Influence of epidemiology, immunosuppressive regimens, clinical presentation, and treatment on kidney transplant outcomes of patients diagnosed with tuberculosis: A retrospective cohort analysis.

Tuberculosis (TB) mortality is high among kidney transplant (KT) recipients. Although local epidemiology is an important factor, diagnostic/therapeutic challenges and immunosuppressive therapy (ISS) may influence outcomes. We analyzed the cumulative incidence (CumI) of TB in KT recipients receiving a variety of ISS with long-term follow-up. Our retrospective single-center cohort study included all KT procedures performed between January 1, 1998, and August 31, 2014, with follow-up until August 31, 2014. Induction therapy was based on perceived immunological risk; maintenance ISS included prednisone and calcineurin inhibitor (CNI) plus azathioprine (AZA), and mycophenolic acid (MPA) or mechanistic target of rapamycin inhibitor (mTORi). Thirty-four patients received belatacept/MPA. KT was performed on 11 453 patients and followed for 1989 (IQR 932 to 3632) days. Among these, 152 patients were diagnosed with TB (CumI 1.32%). Median time from KT to TB was 18.8 (IQR 7.2 to 60) months, with 59% of patients diagnosed after the first year. Unadjusted analysis revealed an increasing confidence interval (CI) of TB (0.94% CNI/AZA vs 1.6% CNI/MPA [HR = 1.62, 95% CI = 1.13 to 2.34, P=.009] vs 2.85% CNI/mTORi [HR = 2.45, 95% CI = 1.49 to 4.32, P<.001] vs 14.7% belatacept/MPA [HR = 13.14, 95% CI = 5.27 to 32.79, P<.001]). Thirty-seven (24%) patients died, and 39 (25.6%) patients experienced graft loss. Cytomegalovirus infection (P=.02) and definitive ISS discontinuation (P<.001) were associated with death. Rejection (P=.018) and ISS discontinuation (P=.005) occurred with graft loss. TB occurred at any time after KT and was influenced by ISS.

790. The Efficacy of the Interferon-γ Releasing Assay-Based Isoniazid Treatment for Preventing Active Tuberculosis in Kidney Transplant Recipients: A Quasi-experimental Study

BackgroundInterferon-γ releasing assays (IGRAs) are useful for diagnosing LTBI. However, there are limited data on the efficacy of IGRA-based isoniazid (INH) treatment with/without back-up tuberculin skin test (TST) to prevent the development of TB in solid-organ transplant recipients.MethodsAll adults patients admitted to a KT unit from January 2014 to December 2016 were retrospectively reviewed in a 2,700-bed, tertiary-care hospital in Seoul, South Korea. The IGRA (i.e., QuantiFERON-In-Tube) with/without TST was performed on all recipients before KT, and 9-month INH treatment was given to patients with clinical risk factors for LTBI regardless of IGRA results. Our hospital policy on LTBI diagnosis and treatment was changed as follows. Period 1 (January 2014–September 2015) adopted IGRA-based INH treatment. We administered INH treatment to all patients with positive IGRA results. Period 2 and period 3 adopted IGRA-based followed by back-up TST-based INH treatment. Period 2 (October 2015–December 2015) included the temporary shortage of Mantoux test, so INH treatment was not given to the patients with positive IGRA since back-up TST was not performed. In Period 3 (January 2016–December 2016), we administered INH treatment to the patients with positive IGRA results followed by back-up TST¡Ã10 mm. The development of TB after KT as the primary endpoint was observed from January 2014 to April 2018.ResultsThe study flow is shown in Figure 1. Of the 1,150 KT recipients, 14 (1.2%) developed TB (incidence rate 0.63 per 100 person-years, 95% CI 0.35–1.06). The median time for TB development was 9.4 months (IQR 4.7–14.5). Seven (3.2%) of 216 patients with positive IGRA without INH treatment developed TB, whereas none of 106 patients with positive IGRA with INH treatment developed TB (rate difference 2.43 per 100 person-years, P = 0.008) and 7 (0.8%) of 828 patients with negative or indeterminate IGRA results developed TB (rate difference 2.0 per 100 person-years, P < 0.001). The number needed to treat (NNT) for IGRA-based INH treatment was 31 (95% CI 18–114).ConclusionIGRA-based INH treatment is effective to prevent the development of TB in KT recipients without clinical risk factors for LTBI with reasonable NNT. Disclosures All authors: No reported disclosures.

Clinical characteristics, risk factors, and outcome of tuberculosis in kidney transplant recipients: A multicentric case-control study in a low-endemic area.

Tuberculosis (TB) is a rare but life-threatening infection after solid organ transplant. The present study was undertaken to assess the clinical features, risk factors, and outcome of TB after kidney transplantation in a low-prevalence area. We conducted a retrospective study, describing all kidney transplant recipients diagnosed with TB between 2005 and 2015 in 3 French centers. For each TB case, 2 controls without TB were identified and matched by center, age, transplant date, and birth country. Risk factors associated with TB were identified and survival estimated. Thirty-two cases and 64 control patients were included among 3974 transplantations. The prevalence of TB was 0.83%. Median age at the time of diagnosis was 64years; 75% were born in a high TB prevalence country, but only 3 had received isoniazid prophylaxis for latent TB infection. TB occurred at a median of 22months after transplantation. On diagnosis, 66% had disseminated infection. Median duration of treatment was 9months. Immunosuppressive therapy changes were necessary in all patients because of drug-drug interactions. Among cases, 5 deaths occurred during follow-up (median duration: 41months), one directly related with TB. Survival was significantly lower in transplant recipients with TB, as compared to controls (P=.001). No predictive factors of tuberculosis after transplantation were statistically significant in univariate analysis. TB in kidney transplant recipients is a rare and late event, but is associated with significantly reduced survival. Our results emphasize the need for systematic screening for LTBI, followed by IPT in high-risk patients.

Spectrum of Infections in Living Donor Kidney Transplant Recipients: An Experience From a Tertiary Center in Nepal

BackgroundKidney transplant recipients are always at risk of infections because they are on lifelong immunosuppressive medications. The spectrum of infections in this special population is not the same as in the general population. Post-transplant infections are extensively studied in the developed world. Publications about post-transplant infections from Nepal are scarce. This study was carried out to study the spectrum of infections, the trends in treatment, and the incidence of tuberculosis in kidney transplant recipients. MethodsThis is a retrospective analysis of the patient data in Tribhuvan University Teaching Hospital, Kathmandu, Nepal. Follow-up data from the first 100 kidney transplant recipients was recorded in a Microsoft Excel worksheet and descriptive analysis was done. ResultsIn the first 100 transplants done until 21 September 2011, 92 patients' data were recorded and 8 patients' data were missing. The mean follow-up period was 61.03 months. The population was 76.09% male (n = 70) and 23.91% female (n = 22). A total of 641 episodes of infections were recorded. Urinary tract infections were the most common type of infection. Escherichia coli was the most common organism isolated (36% of all cultures). There were 17 (2.65%) episodes of viral and 42 (6.6%) episodes of fungal infections. Tuberculosis was diagnosed in 6 (6.5%) patients. ConclusionUrinary tract infection is the most common type of infection in post-kidney transplant patients. Quinolones were the most common agents used to treat urinary tract infections. The incidence of tuberculosis in kidney transplant recipients is 6.5% in 5 years' follow-up.

Clinical features and outcomes of tuberculosis in kidney transplant recipients in Brazil: a report of the last decade

Among kidney transplant recipients (KTRs), tuberculosis is one of the most common opportunistic infections and is associated with high morbidity and mortality. The aim of this study was to describe the incidence, clinical features, and prognosis of tuberculosis in KTRs. Retrospective single-center observational study involving all cases of tuberculosis in KTRs between 2000 and 2010. Of the 1549 KTRs evaluated, 43 (2.8%) developed tuberculosis, translating to an annual incidence of 803 cases/100 000 patients, considerably higher than that reported for the general population of Brazil. The median time to tuberculosis (TB) onset after transplantation was 196 d (range, 19-3626 d). Of the KTRs with tuberculosis, 67% became infected within the first year post-transplant, 74% had pulmonary tuberculosis, and 7% had a previous history of active tuberculosis. No tuberculosis prophylaxis was employed before or after transplantation. The most common symptoms were fever (in 79%), cough (in 35%), and dyspnea (in 16%). The median time from the onset of symptoms to the start of treatment was 28 d. The median duration of antituberculosis therapy was 196 d. In 15 patients (35%), the immunosuppressive therapy was reduced, and the incidence of acute rejection was higher in patients with tuberculosis than in those without (44% vs. 28%). Mortality during tuberculosis treatment was 12% (5 cases), and all five deaths were attributed to tuberculosis. Ten-yr death-censored graft survival and patient survival were similar between patients with tuberculosis and those without. Among KTRs, symptoms of tuberculosis are often attenuated, which leads to delayed diagnosis, and tuberculosis-related mortality remains high.

Peculiarities of tuberculosis in kidney transplant recipients

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.

Hepatitis C virus, an important risk factor for tuberculosis in immunocompromised: experience with kidney transplantation

Little is known about the role of hepatitis C virus (HCV) infection in the development of tuberculosis (TB) in patients with immunosuppression. We performed a retrospective case-control study (1:4) to investigate by univariate and multivariate logistic regression analysis the importance of HCV infection in the development of TB in a cohort of kidney transplant recipients (KTR). TB was diagnosed in 16 out of 2012 (0.8%) KTR between 1976 and 2004. The percentage of HCV-positive patients was significantly higher in cases than in controls (56.3% vs. 18.8%; P=0.02). By multivariate analysis, the only two independent risk factors associated with the development of TB were the presence of HCV infection (P=0.003; OR=6.5; 95% CI 1.9-23) and serum creatinine over 1.5 mg/dl (P=0.03; OR=4.8; 95% CI 1.1-21). HCV infection and chronic graft dysfunction are important risks factors for TB in KTR.