Mycobacterium Tuberculosis Infection Incidence in Hospitalized Renal Transplant Patients in the United States, 1998–2000

The incidence, risk factors, and prognosis for Mycobacterium tuberculosis (MTB) infection have not been reported in a national population of renal transplant recipients. We performed a retrospective cohort study of 15,870 Medicare patients who received renal transplants from January 1, 1998 to July 31, 2000. Cox regression analysis derived adjusted hazard ratios (AHR) for factors associated with a diagnosis of MTB infection (by Medicare Institutional Claims) and the association of MTB infection with survival. There were 66 renal transplant recipients diagnosed with tuberculosis infection after transplant (2.5 cases per 1000 person years at risk, with some falling off of cases over time). The most common diagnosis was pulmonary TB (41 cases). In Cox regression analysis, only systemic lupus erythematosus (SLE) was independently associated with TB. Mortality after TB was diagnosed was 23% at 1 year, which was significantly higher than in renal transplant recipients without TB (AHR, 4.13, 95% CI, 2.21, 7.71, p < 0.001). Although uncommon, MTB infection is associated with a substantially increased risk of mortality after renal transplantation. High-risk groups, particularly those with SLE prior to transplant, might benefit from intensified screening.     

Mycobacterium tuberculosis infection in renal transplant recipients

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 isoniazid-related 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.     

Mycobacterium tuberculosis infection in solid organ transplant recipients: experience from a single center in China

OBJECTIVE: We sought to explore the prevalence, clinical manifestations, diagnostic procedures, and treatment of tuberculosis (TB) after solid organ transplantation. PATIENTS AND METHODS: In this study, we retrospectively analyzed data of 1947 renal transplant recipients and 85 liver transplant recipients. RESULTS: TB developed in 28 organ transplant recipients with a prevalence of 1.38% (28/2032). The median interval between transplantation and development of TB was 32 months (range, 1-142 months). Mycobacterium tuberculosis isolation, histologic signs of caseating granulomas, and TB-DNA detection directly supported the diagnosis in 10 (35.71%), 7 (25.00%), and 5 (17.86%) patients, respectively. In addition, 6 patients (21.43%) highly suspected of TB infection received tentative antituberculosis treatment with favorable responses. Most renal transplant recipients (22/25; 78.57%) received isoniazid, rifampicin (or rifabutin), and ethambutal (or pyrazinamide) for a mean duration of 10 months (range, 6-14 months). Three liver transplant recipients received a different protocol: isoniazid, rifabutin, ethambutal, and ofloxacin for 3 months; then isoniazid and rifabutin for 6 months. Upon follow-up, 8 subjects (28.57%) died; 5 of the deaths were related to TB. During the antituberculosis therapy, toxic hepatitis was seen in 12 patients (42.86%); cyclosporine levels decreased in 15 patients (53.57%); and allograft rejection developed in 6 of them. CONCLUSIONS: The peak incidences of TB in liver and kidney transplantations are in the first year and after the first year posttransplantation, respectively. Response to antituberculosis treatment should be considered to make a diagnosis among patients highly suspected of TB infections. Except in special circumstances, antituberculosis treatment protocols including isoniazid and rifampicin for about 10 months seem significantly effective and tolerable for non-liver transplant patients. Fluoroquinolones should be emphasized in posttransplantation TB treatment.     

The influence of non‐HLA antibodies directed against angiotensin II type 1 receptor (AT1R) on early renal transplant outcomes

Non‐HLA antibodies (Abs) targeting vascular receptors are thought to have an impact on renal transplant injury. Anti‐angiotensin II type 1‐receptor‐activating antibodies (anti‐AT1R) have been mentioned to stimulate a severe vascular rejection, but the pretransplant screening has not been introduced yet. The aim of our study was to assess the incidence and importance of anti‐AT1R antibodies and their influence on renal transplant in the 1st year of observation. We prospectively evaluated the presence of anti‐AT1R antibodies in 117 consecutive renal transplant recipients in pre‐ and post‐transplant screening. Anti‐AT1R antibodies were observed in 27/117 (23%) of the analyzed recipients already before transplantation. The function of renal transplant was considerably worse in anti‐AT1R(+) group. The patients with anti‐AT1R Abs >9 U/ml lost their graft more often. Biopsy‐proven AR was described in 4/27 (15%) pts in the anti‐AT1R(+) group and 13/90 (14.4%) in the anti‐AT1R(?) group, but more severe cases of Banff IIB or antibody‐mediated rejection (AMR) were more often observed in anti‐AT1R (+) 4/27 (15%) vs. 1/90 (1.1%) in anti‐AT1R(+) (P = 0.009). Patients with anti‐AT1R Abs level >9 U/ml run a higher risk of graft failure independently of classical immunological risk factors. The recipients with anti‐AT1R Abs developed more severe acute rejections described as IIB or AMR in Banff classification. More recipients among the anti‐AT1R‐positive ones lost the graft. Our study suggests monitoring of anti‐AT1R Abs before renal transplantation for assessment of immunologic risk profiles and the identification of patients highly susceptible to immunologic events, graft failure, and graft loss.     

The potential role of C-reactive protein in distinguishing cytomegalovirus from tuberculosis and bacterial infections in renal transplant recipients

Abstract: Introduction: The delay in the diagnosis of infections can be deleterious in renal transplant recipients. Thus, laboratory tests leading to an earlier diagnosis are very useful for these patients. Purpose: To assess the behavior of C‐reactive protein (CRP) in renal transplant recipients with a diagnosis of cytomegalovirus (CMV) infection, tuberculosis (TB) and bacterial infection (BI). Methods: A retrospective analysis of 129 patients admitted at our hospital, from 2006 to 2008 because of CMV, TB or BI, was carried out. Appropriate statistical analysis was done and values were expressed as medians, range. Results: When CRP levels were compared among the groups with CMV disease, TB or BI, the group with CMV disease presented lower levels of CRP (18.4 mg/L, 0.28–44 mg/L) than the TB and BI (p < 0.05) groups. The area under the receiver‐operating characteristics curve, distinguishing CMV disease from TB/BI, was 0.96 (p < 0.0001), resulting in 100% sensitivity and 90.63% specificity to detect CMV disease when CRP < 44.5 mg/L. The subgroup analysis of CMV infection showed increasing levels of CRP (0.28, 16 and 29.5 mg/L) in the asymptomatic, symptomatic and invasive disease subgroups, respectively (p < 0.05). Conclusion: The measurement of CRP levels may be a useful tool for differentiating CMV infection from the other types (bacterial or TB) of infection in kidney transplant recipients.     

Desensitization for renal transplantation: depletion of donor‐specific anti‐HLA antibodies,preservation of memory antibodies,and clinical risks

Desensitization protocols reduce donor‐specific anti‐HLA antibodies (DSA) and enable renal transplantation in patients with a positive complement‐dependent cytotoxic cross‐match (CDC‐CXM). The effect of this treatment on protective antibody and immunoglobulin levels is unknown. Thirteen patients with end‐stage renal disease, DSA and positive CDC‐CXM underwent desensitization. Sera collected pre‐ and post‐transplantation were analysed for anti‐tetanus and anti‐pneumococcal antibodies, total immunoglobulin (Ig) levels and IgG subclasses and were compared to healthy controls and contemporaneous renal transplant recipients treated with standard immunosuppression alone. Ten patients developed negative CDC‐CXM and enzyme‐linked immunosorbent assay (ELISA) and underwent successful transplantation. Eight recipients achieved good graft function without antibody‐mediated or late rejection, BK virus or cytomegalovirus infection. One patient had primary non‐function due to recurrent oxalosis, and one patient with immediate graft function died from septicaemia. Seven recipients required post‐operative transfusion and three developed septicaemia. DSA remained negative by ELISA at 12 months, but were detectable by Luminex^®. Anti‐tetanus and anti‐pneumococcal antibodies, total Ig and IgG subclasses were below the normal range but comparable to levels in renal transplant recipients who had not undergone desensitization. Desensitization protocols effectively reduce DSA and allow successful transplantation. Post‐operative bleeding and short‐term infectious risk is increased. Protective antibody and serum immunoglobulin levels are relatively preserved.     

Soluble CD30 and ELISA‐detected human leukocyte antigen antibodies for the prediction of acute rejection in pediatric renal transplant recipients

Biomarker‐based post‐transplant immune monitoring for the prediction of impending graft rejection requires validation in specific patient populations. Serum of 28 pediatric renal transplant recipients within the framework of a well‐controlled prospective randomized trial was analyzed pre‐ and post‐transplant for soluble CD30 (sCD30), a biomarker reflecting mainly T‐cell reactivity, and anti‐human leukocyte antigen (anti‐HLA) antibody reactivity, a biomarker for B‐cell activation. A sCD30 concentration ≥40.3 U/ml on day 14 was able to discriminate between patients with or without biopsy‐proven acute rejection (BPAR) with a sensitivity of 100% and a specificity of 76%. Six of seven patients (86%) with BPAR showed a sCD30 above this cut‐off, whereas only 3/21 patients (14%) without BPAR had a sCD30 above this cut‐off (P = 0.004). For pre‐ and post‐transplant anti‐HLA class II reactivities by enzyme‐linked immunosorbent assay, a cut‐off value of 140 optical density was able to discriminate rejecters from nonrejecters with a sensitivity of 86% or 71% and a specificity of 81% or 90%, respectively. Withdrawal of steroids was associated with a approximately twofold higher serum sCD30 compared to controls, but did not affect anti‐HLA reactivities. An increased post‐transplant sCD30 serum concentration and positive pre‐ and post‐transplant anti‐HLA class II reactivities are informative biomarkers for impending BPAR in pediatric renal transplant recipients. (TWIST, Clinical Trial No: FG‐506‐02‐43)     

Mycobacterium tuberculosis infection and laboratory diagnosis in solid-organ transplant recipients

Tuberculosis (TB) is an unusual infection in transplant recipients. We evaluated (i) the frequency of TB, (ii) the duration to develop the TB infection, and (iii) clinical consequences, in 380 solid-organ recipients from January 1995 to December 2000. A total of 10 (2.63%) patients (eight renal, two liver transplant recipients) were found to have post-transplantation TB. The frequency of TB in this patient population is 8.5-fold higher than the prevalance in the general Turkish population. Tuberculosis developed within 2-33 months after transplantation, with a median of 15 months. In all of these 10 patients, Mycobacterium tuberculosis (MTB) was isolated from the culture. All the patients continued to have low dose immunosuppressive treatment, and also quadriple antituberculosis treatment [isoniazid (INH), rifampin (RIF), pyrazinamide (PRZ) and ethambutol (ETB)] has been given. The two recipients had died of disseminated form of TB. Relapse was detected in one patient 6 months after the completion of the treatment. As post-transplant TB infection develops mostly within the first year after transplantation, clinicians should be more careful for early and fast diagnosis and treatment should be started immediately.     

Tuberculosis in Thai renal transplant recipients: a 15-year experience

OBJECTIVE: Tuberculosis (TB) is a leading cause of morbidity and mortality in renal transplant recipients, especially in developing countries. Its incidence and characteristics remain unknown in Thai recipients. This study sought to determine the incidence, characteristics, risk factors, and outcome of TB in Thailand. METHODS: We retrospectively reviewed case records of all renal transplant recipients from 1992 to 2007 to record demographic information, transplant characteristics, median time to diagnosis of TB, and outcomes. RESULTS: Among 270 recipients, 9 (3.84%, 95% confidence interval [CI] 1.18%-5.49%) developed TB. Their median age was 40 years (range = 23-62 years) and median time from transplantation to diagnosis was 36 months (range = 4-115 months). Although pulmonary TB was the most common form (56%), 2 patients (22%) developed extrapulmonary disease. Disseminated TB occurred in 2 patients (22%). The diagnosis was made on respiratory specimen cultures in 3 cases (33.3%) and body fluid cultures in 3 (33.3%). Five patients (55.6%) were successfully treated with four-drug combination therapy. Two of the other subjects (22.2%) who received triple therapy were noncompliant, succumbing to graft failure and sepsis. Blood group AB (odds ratio [OR] 10.95, 95% CI 1.57-76.60) and use of tacrolimus rescue therapy (OR 9.68, 95% CI 2.13-43.94) were associated with an elevated risk of TB. CONCLUSION: TB is common among Thai renal transplant recipients with an incidence 27 times higher than that of the general Thai population. The extrapulmonary form in particular occurs more frequently with an increased risk of mortality.     

A high intrapatient variability in tacrolimus exposure is associated with poor long‐term outcome of kidney transplantation

Tacrolimus is a critical dose drug with a considerable intrapatient variability (IPV) in its pharmacokinetics. We investigated whether a high IPV in tacrolimus exposure is associated with adverse long‐term renal transplantation outcomes. Tacrolimus IPV was calculated from predose concentrations measured between 6 and 12 months post ‐ transplantation of 808 renal transplant recipients (RTRs) transplanted between 2000 and 2010. One hundred and eighty‐eight (23.3%) patients reached the composite end point consisting of graft loss, late biopsy‐proven rejection, transplant glomerulopathy, or doubling of serum creatinine concentration between month 12 and the last follow‐up. The cumulative incidence of the composite end point was significantly higher in patients with high IPV than in patients with low IPV (hazard ratio: 1.41, 95% CI: 1.06–1.89; P = 0.019). After the adjustment for several factors, the higher incidence of the composite end point for RTRs with a high IPV remained statistically significant (hazard ratio: 1.42, 95% CI: 1.06–1.90; P = 0.019). Younger recipient age at transplantation, previous transplantation, worse graft function (at month 6 post‐transplantation), and low mean tacrolimus concentration at 1 year post‐transplantation were additional predictors for worse long‐term transplant outcome. A high tacrolimus IPV is an independent risk factor for adverse kidney transplant outcomes that can be used as an easy monitoring tool to help identify high‐risk RTRs.     

Racial differences in incident de novo donor‐specific anti‐HLA antibody among primary renal allograft recipients: results from a single center cohort study

Controversy exists as to whether African American (AA) transplant recipients are at risk for developing de novo donor‐specific anti‐human leucocyte antigen (HLA) antibody (dnDSA). We studied 341 HLA‐mismatched, primary renal allograft recipients who were consecutively transplanted between 3/1999 and 12/2010. Sera were collected sequentially pre‐ and post‐transplant and tested for anti‐HLA immunoglobulin G (IgG) via single antigen bead assay. Of the 341 transplant patients (225 AA and 116 non‐AA), 107 developed dnDSA at a median of 9.2 months post‐transplant. AA patients had a 5‐year dnDSA incidence of 35%. This was significantly higher than the 5‐year dnDSA incidence for non‐AA patients (21%). DQ mismatch (risk) and receiving a living‐related donor (LRD) transplant (protective) were transplant factors associated with dnDSA. Within the AA patient cohort, HLA‐DQ mismatch, not‐receiving a LRD transplant, nonadherence and BK viraemia were the most common factors associated with early dnDSA (occurring <24 months post‐transplant). Nonadherence and pretransplant diabetes history were the strong precursors to late dnDSA. Despite the higher rates of dnDSA in the AA cohort, post‐dnDSA survival was the same in AA and non‐AA patients. This study suggests that DQ matching, increasing LRD transplantation in AA patients and minimizing under‐immunosuppression will be key to preventing dnDSA.     

Post‐transplant malignancy: a burdensome complication in renal allograft recipients in Korea

Cancer has been a serious complication of kidney transplantation ever since the outcome of this procedure improved. The incidence of cancer among kidney transplant (KT) recipients is increasing, and these patients have a higher risk of developing cancer than the general population. The present retrospective cohort study compared the cancer rate of kidney recipients in a single transplantation center in Korea with that in healthy Korean individuals using the standardized incidence ratio (SIR). The medical records of all 2365 patients who underwent renal transplantation between 1989 and 2009 were reviewed retrospectively. During the study period, 136 renal allograft recipients developed 140 malignancies. The cumulative cancer incidence one, five, 10, and 15 yr post‐transplantation was 0.60%, 3.24%, 5.69%, and 8.90%, respectively. Non‐Hodgkin lymphoma (NHL) and thyroid cancer were the most common cancers after renal transplantation, occurring significantly more frequently than in the general Korean population. The SIR of all cancers was 1.9 (women: 2.4; men: 1.6). Comparison with similar studies in Korea and other countries suggests transplant center‐related differences dictate post‐transplant malignancy incidence more strongly than ethnic or geographic factors. Early surveillance programs for de novo malignancies after kidney transplantation focusing on kidney‐transplantation‐related tumors and postoperative time period should be established.     

Mineral metabolism in renal transplant recipients discontinuing cinacalcet at the time of transplantation: a prospective observational study

Evenepoel P, Sprangers B, Lerut E, Bammens B, Claes K, Kuypers D, Meijers B, Vanrenterghem Y. Mineral metabolism in renal transplant recipients discontinuing cinacalcet at the time of transplantation: a prospective observational study.
Clin Transplant 2011 DOI: 10.1111/j.1399‐0012.2011.01524.x.
© 2011 John Wiley & Sons A/S. Abstract: Background: The calcimimetic cinacalcet is approved for treating secondary hyperparathyroidism in patients with chronic kidney disease on dialysis. Biochemical profiles and clinical outcomes in patients discontinuing cinacalcet at the time of transplantation are scarce. Methods: We performed a prospective observational cohort study, including 303 incident renal transplant recipients, of whom 21 were on cinacalcet treatment at the time of transplantation. Parameters of mineral metabolism and incidence of parathyroidectomy and nephrocalcinosis in patients discontinuing cinacalcet at the time of transplantation patients (“cinacalcet +”) were compared to cinacalcet‐naïve patients (“cinacalcet –”). Mean follow‐up was 35.6 ± 15.8 months. Results: At the time of transplantation, parameters of mineral metabolism were similar in both groups. Conversely, at month 3, serum ionized calcium (p = 0.0007), calcitriol (p = 0.02), biointact parathyroid hormone (p = 0.06) levels and urinary fractional excretion of phosphorus (p = 0.06) were higher, while serum phosphorus levels (p = 0.06) were lower in “cinacalcet +.” Analysis based on matching at the time of initiation showed that the course of post‐transplant mineral metabolism in cinacalcet‐treated patients (median treatment period 12.5 months) vs. cinacalcet‐naïve patients was identical. “Cinacalcet +” patients are characterized by a high‐incidence proportion of both post‐transplant nephrocalcinosis (45% at month 3) and parathyroidectomy (28.6%). No difference in renal function was observed between “cinacalcet +” and “cinacalcet?” patients. Conclusion: Cinacalcet does not affect the course of secondary hyperparathyroidism in patients awaiting kidney transplantation. Biochemical profiles and a high parathyroidectomy rate suggest rebound hyperparathyroidism in renal transplant recipients discontinuing cinacalcet at the time of transplantation, which may be related to the short exposure time specific to this population. Risk/benefit studies are urgently required to define the role of continued calcimimetic treatment in renal transplant recipients and to determine the optimal treatment of secondary hyperparathyroidism in patients listed for transplantation.     

Diagnosis and Management of Tuberculosis in Transplant Donors: A Donor‐Derived Infections Consensus Conference Report†

Mycobacterium tuberculosis is a ubiquitous organism that infects one‐third of the world's population. In previous decades, access to organ transplantation was restricted to academic medical centers in more developed, low tuberculosis (TB) incidence countries. Globalization, changing immigration patterns, and the expansion of sophisticated medical procedures to medium and high TB incidence countries have made tuberculosis an increasingly important posttransplant infectious disease. Tuberculosis is now one of the most common bacterial causes of solid‐organ transplant donor‐derived infection reported in transplant recipients in the United States. Recognition of latent or undiagnosed active TB in the potential organ donor is critical to prevent emergence of disease in the recipient posttransplant. Donor‐derived tuberculosis after transplantation is associated with significant morbidity and mortality, which can best be prevented through careful screening and targeted treatment. To address this growing challenge and provide recommendations, an expert international working group was assembled including specialists in transplant infectious diseases, transplant surgery, organ procurement and TB epidemiology, diagnostics and management. This working group reviewed the currently available data to formulate consensus recommendations for screening and management of TB in organ donors.     

Durability of the hepatitis B vaccination in pediatric renal transplant recipients

Since hepatitis B virus (HBV) vaccine implementation, HBV infection has significantly decreased. However, adult renal transplant recipients show a higher rate of seroreversion compared to the general population, leading to HBV infection risk. Data are limited in pediatric renal transplant recipients. Retrospective data were collected to determine the seroprotection and durability of HBV vaccination in pediatric renal transplant patients from 2004 to 2014. One hundred subjects were categorized based on pre‐ and post‐transplant hepatitis B surface antibody (HBsAb). Pretransplant, 85 recipients (85%) had a positive HBsAb compared to 15 (15%) with negative HBsAb. In univariable analyses, other than age (P < .05) no significant differences existed pretransplant by demographics, pretransplantation dialysis, or number of vaccinations. Of the 85 pretransplantation responders, 53 (62%) remained HBsAb positive post‐transplantation, 28 (32%) seroreverted, and 4 developed indeterminate titers. All seroreversions occurred within 5 years post‐transplant. Receipt of a living donor organ had higher risk of reversion (P = .005). No significant differences were found in demographics, pretransplantation dialysis, vaccination number, or acute rejection. Despite vaccination, 15% of pediatric renal transplant candidates were seronegative, and an additional 32% lost seroprotection within 5 years post‐transplantation leaving nearly half of transplant recipients at risk for HBV infection.     

Inferior graft survival of hepatitis B core positive grafts is not influenced by post‐transplant hepatitis B infection in liver recipients—A 35‐year single‐center experience

Nonoptimal liver grafts, and among them organs from anti‐HBc+ donors, are increasingly used for liver transplantation. In this retrospective study including 1065 adult liver transplantations performed between 1977 and 2012, we analyzed long‐term patient and graft survival and occurrence of HBV infection. A total of 52 (5.1%) patients received an anti‐HBc+ graft. The 10‐year graft and patient survival of these recipients were 50.9% and 59.0% compared to 72.0% and 76.5% (P = 0.001; P = 0.004) of patients receiving anti‐HBc‐ grafts, respectively. Cox regression model showed that high urgency allocation (P = 0.003), recipient age (P = 0.027), anti‐HCV+ recipients (P = 0.005), and anti‐HBc+ organs (P = 0.048) are associated with decreased graft survival. Thirteen of 52 (25.0%) patients receiving anti‐HBc+ grafts developed post‐transplant HBV infection within a mean of 2.8 years. In this study, antiviral prophylaxis did not have significant impact on HBV infection, but long‐term survival (P = 0.008). Development of post‐transplant HBV infection did not affect adjusted 10‐year graft survival (100% vs. 100%; P = 1). Anti‐HBc+ liver grafts can be transplanted with reasonable but inferior long‐term patient and graft survival. The inferior graft survival is not, however, related with post‐transplant HBV infection as long as early diagnosis and treatment take place.     

Corticosteroid elimination in simultaneous liver–kidney transplantation recipients

Abstract: Background: Simultaneous liver–kidney transplantation (SLK) has more than doubled since 2002. While less common in kidney transplant alone recipients (KTA), corticosteroid discontinuation is performed routinely in liver transplantation, raising the question of optimal immunosuppression for SLK recipients. Methods: A retrospective case series of 16 SLK recipients under a steroid withdrawal protocol was performed to compare short‐term outcomes to a contemporaneous cohort of 32 KTA recipients. Results: In 69% of SLK recipients, corticosteroids were eliminated compared to 3% of KTA recipients, p < 0.0001. When comparing SLK and KTA recipients one yr post‐transplant, there were no significant differences in renal graft rejection (23.1% vs. 6.3%), death‐censored renal graft survival (100% vs. 97%), estimated glomerular filtration rate (74.4 vs. 62.6 mL/min), serum creatinine (1.10 vs. 1.39 mg/dL), or maintenance immunosuppression, respectively. Conclusions: Corticosteroids may be withdrawn safely in SLK recipients with one‐yr renal outcomes comparable to a KTA cohort.     

Incidence,characteristics, and treatment outcomes of mycobacterial diseases in transplant recipients

The incidence, clinical characteristics, and treatment outcomes of tuberculosis (TB) and nontuberculous mycobacterial (NTM) disease developed after transplantation (TPL) in transplant recipients were investigated retrospectively. Between 1996 and 2013, 7342 solid‐organ transplantation and 1266 hematopoietic stem cell transplantation were performed at a tertiary referral center in South Korea. Among them, TB and NTM disease developed in 130 and 22 patients, respectively. The overall incidence of TB was 257.4 cases/100 000 patient‐years (95% confidence interval [CI], 215.1–305.7) and that of NTM disease was 42.7 cases/100 000 patient‐years (95% CI, 26.8–64.7). The median interval from organ TPL to the development of mycobacterial disease was 8.5 months (95% CI, 6.3–11.4) in recipients with TB patients and 24.2 months (95% CI, 13.5–55.7) in those with NTM, respectively. Among NTM patients, Mycobacterium avium–intracellulare complex was the most common causative organism, and nodular bronchiectatic type (77.8%) was the most frequent radiologic feature. Favorable treatment outcome was achieved in 83.7% (95% CI, 76.4–89.1) and 68.8% (95% CI, 44.4–85.8) of TB and NTM patients, respectively (P = 0.166). In conclusion, the overall incidence of TB was higher than that of NTM disease in transplant recipients and treatment outcomes were favorable in both drug‐susceptible TB and NTM patients.     

肾移植术后结核病的临床特征分析及诊断和治疗的单中心经验

目的 分析和总结肾移植术后结核病的临床特征及诊断和治疗的经验.方法 2842例肾移植受者中,术后有61例诊断为结核病,回顾性分析这61例患者的临床资料.结果 肾移植术后结核病的临床特点如下:(1)发病时间为术后1～156个月,发生率达2.1％(61/2842),术后1年内结核病发生率为54.1％(33/61);(2)结核病灶最常见的部位为肺部(77.0％,47/61),肺外结核的发病率高(60.7％,37/61),其中淋巴结结核14例(23.0％)、结核性胸膜炎8例(13.1％)、移植肾结核7例(11.5％);(3)术后结核病的临床表现主要为发热、咳嗽、咳痰、消瘦及淋巴结肿大;(4)结核菌素试验阴性率高(91.8％,56/61),影像学检查在结核病的诊断上具有重要意义;(5)结核病患者均采用“个体化”抗结核治疗方案,包括活动性结核感染的治疗及诊断性抗结核治疗两种方案.肝功能损害(16.4％)、肾功能损害(39.3％)及周围神经毒性(3.3％)是抗结核治疗过程中出现的主要不良反应,也是抗结核治疗失败的主要原因;(6)术前存在陈旧性结核,术后结核病复发的可能性增加(23.5％,4/17);(7)术后结核病患者常伴有细胞免疫功能减弱,常继发细菌、病毒及真菌的重叠感染(19.7％);(8)结核病患者术后1年人、肾存活率分别为85.2％和8.7％,3年人、肾存活率分别为85.2％和75.4％,总体累积死亡率达14.8 ％(9/61),重叠感染是肾移植术后结核病患者死亡的主要原因(66.7％,6/9).结论 我国肾移植受者术后并发结核病的风险较大,且容易合并各种严重并发症致患者死亡,早期诊断和治疗对提高患者的长期存活率具有重要意义.     

Posttransplant lymphoproliferative disorders in renal allograft recipients: report of 53 cases of a French multicenter study

Abstract New immunosuppressive therapies are currently being developed in renal transplantation and their relative risk in terms of post‐transplant lymphoproliferative disorders (PTLD) must be carefully evaluated. For this purpose, a French registry of PTLD occurring after renal transplantation was set up. Among 10000 patients presently followed up in 30 French renal transplantation centers, we prospectively identified 53 new PTLD (0.5 %) since January 1998. Patients (34 male, 19 female) ranged from 3 to 72 years (mean age: 46 years), and the median time between grafting and diagnosis of PTLD was 63 months (2 months to 14 years). Ninety percent of recipients were Epstein‐Barr virus (EBV) positive before transplantation. Most patients received a quadruple sequential therapy with polyclonal anti‐lymphocyte globulin. Sites involved in PTLD were isolated lymph nodes in 13 cases, stomach or bowel in 10 cases, allograft in 14 cases, central nervous system in 6 cases, oropharynx in 4 cases, and skin or mucosa in 4 cases. Only three PTLD expressed markers of T lineage. Out of 40 studied tumors, 31 (78%) were EBV positive. Tumors were classified as polymorph in 26 cases and monomorph in 23 cases. Genotype studies in 18 PTLD showed a monoclonal pattern in 13 cases. In most patients, treatment consisted of reduction of immune suppression, 21 patients were given additional anti‐viral therapy, 13 patients had anti‐CD20, 23 patients underwent chemotherapy, and 4 patients were given cerebral radiotherapy. Five patients underwent transplantectomy. Sixteen patients (30 %) died within the 1st year and 7 patients returned to dialysis (13 %). The outcome of patients with PTLD remains poor, and the optimal approach to therapy is largely unknown. This ongoing registry is not only a national observatory but also a task force designed to improve the treatment strategy of PTLD.