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.     

The burden of new-onset diabetes mellitus after transplantation

The clinical impact of new-onset diabetes mellitus (NODM) is frequently underestimated by clinicians. NODM occurs in approximately 15-20% of renal transplant patients and 15% of liver transplant recipients. Diabetes after transplantation is a leading risk factor for cardiovascular events, with a higher prognostic value than in the non-transplant population. NODM also appears to have a negative influence on graft function, and graft survival rates after renal transplantation are significantly lower in patients who develop diabetes than in controls. Patient mortality following renal transplantation is generally found to be higher in patients with NODM, due to increased cardiovascular and peripheral vascular disease, accelerated graft deterioration and diabetes-related complications, notably infection. A renal registry analysis has reported an increase of 87% in risk of death following onset of NODM. There is also limited evidence that NODM is associated with increased risk of death in liver transplant patients. The relative incidence and severity of diabetic complications in transplant recipients have not been assessed rigorously in a clinical trial but registry data indicate that 20% of renal transplant patients with NODM experience at least one clinically significant diabetic complication within three years. Financially, the additional healthcare costs incurred over the first two years following onset of NODM amount to 21,500 dollars. Routine pre-transplant assessment of diabetic risk, with requisite modification of lifestyle, glycaemic monitoring and immunosuppressive regimens, and coupled with standardized, aggressive hypoglycaemic management as necessary, offers an important opportunity to alleviate the burden of NODM for transplant patients.     

A Case of Multidrug-Resistant Monoarticular Joint Tuberculosis in a Renal Transplant Recipient

Tuberculosis (TB) is a common opportunistic infection after renal transplantation. The risk of TB in renal transplant recipients is reported to be 20 to 74 times higher than in the general population. Although extrapulmonary TB occurs frequently, isolated ankle joint TB is a rare form of extrapulmonary TB infection. It is often difficult to diagnose because of its atypical presentation; management is complex, especially with multidrug-resistant TB, the need for a prolonged course of therapy, and the risks of drug interactions and drug toxicity. We report herein a case of a 60-year-old female renal allograft recipient who developed multidrug-resistant ankle joint TB 11 months after her deceased donor renal transplantation. She presented to the emergency department with escalating pain and swelling of the left ankle, difficulty in ambulation, and a low-grade fever. An x-ray of the ankle revealed an effusion and soft tissue swelling. A synovial fluid culture was performed which tested positive for acid fast bacilli which grew a multidrug-resistant form of Mycobacterium tuberculosis. She was initially treated with isoniazid, rifampin, ethambutol, and pyrazinamide; then therapy was tailored secondary to the resistant nature of the organism. She received a combination of extensive debridement of the joint and institution of second-line anti-TB therapy with pyrazinamide, ethambutol, moxifloxacin, and ethionamide. To our knowledge, no other cases of multidrug-resistant TB have been reported in the literature after renal transplantation. This case shows both an atypical presentation of TB and the difficulties in managing a transplant patient with this disease.     

Urinary tract infections after renal transplantation: a retrospective review at two US transplant centers

Urinary tract infections (UTIs) are the most common infectious complication following renal transplantation. Previous studies uniformly report that renal transplant recipients develop UTIs more often than the general population, but widely differ on how frequently UTIs occur after transplantation. These studies also disagree on the risk factors associated with developing post-transplant UTIs, as well as the effect that UTIs may have on graft outcomes and patient mortality. We performed a retrospective cohort study including all the adult patients who received a renal transplant at two US transplant centers from January 1996 to December 2002 (500 patients). Two hundred and thirteen (43%) patients developed one or more post-transplant UTIs over a mean follow-up period of 42 months. Significant risk factors for post-transplant UTIs were advanced age, female gender, reflux kidney disease, use of azathioprine and cadaveric donor. UTIs did not increase risk for renal graft loss, but were associated with increased mortality (3.5 odds ratio, 95% confidence interval 1.68-7.23). We conclude UTIs may be associated with an increased mortality risk in renal transplant recipients. Prevention of UTIs in high-risk renal transplant patients or those with recurrent UTIs may possibly decrease post-transplant mortality.     

Hospitalized Atrial Fibrillation After Renal Transplantation in the United States

Renal transplant recipients have a high incidence of hypertension, a known risk factor for atrial fibrillation (AF), as well as factors that could increase their risk of AF. However, the incidence of, risk factors for, and mortality associated with AF after renal transplantation have not been reported. We present a historical cohort study of 39 628 renal transplant recipients in the United States Renal Data System between 1 July 1994 and 30 June 1998. Data source: USRDS files through May 2000. Associations with hospitalizations for a primary diagnosis of AF (ICD-9 codes 427.31) after renal transplant were assessed by Cox Regression analysis. Tacrolimus was not approved for use by the FDA during the time-frame of the study. The incidence of AF after renal transplantation was 5.8 episodes/1000 person-years. In Cox Regression analysis, recipients who were older age, experienced graft loss, rejection, had higher body mass index, renal failure due to hypertension, and cyclosporine use (vs. tacrolimus use) were associated with increased risk of hospitalized AF. Atrial fibrillation was not uncommon after renal transplantation, and was associated with increased risk of mortality, primarily from cardiovascular disease. The strongest risk factors for AF after renal transplantation were older age, allograft rejection, graft loss and obesity.     

Hospitalizations for bacterial endocarditis after renal transplantation in the United States.

PURPOSE: The national rate of and risk factors for bacterial endocarditis in renal transplant recipients has not been reported. METHODS: Retrospective registry study of 33,479 renal transplant recipients in the United States Renal Data System (USRDS) between 1 July 1994 and 30 June 1997. Hospitalizations for a primary diagnosis of bacterial endocarditis (ICD-9 codes 421.x) within three years after renal transplant were assessed. RESULTS: Renal transplant recipients had an unadjusted incidence ratio for endocarditis of 7.84 (95% confidence interval 4.72-13.25) in 1996. In multivariate analysis, a history of hospitalization for valvular heart disease (adjusted odds ratio (AOR), 25.81, 95% confidence interval 11.28-59.07), graft loss (AOR, 2.81, 95% CI 1.34-5.09), and increased duration of dialysis prior to transplantation were independently associated with hospitalizations for bacterial endocarditis after transplantation. Hospitalization for endocarditis was associated with increased patient mortality in Cox Regression analysis, hazard ratio 4.79, 95% CI 2.97-6.76. CONCLUSIONS: The overall incidence of bacterial endocarditis was much greater in renal transplant recipients than in the general population, although it is still relatively infrequent. Independent risk factors for bacterial endocarditis in the renal transplant recipients were identified, the most significant of which was valvular heart disease. Endocarditis substantially impacts renal transplant recipient survival.     

Kidney Transplantation in Previous Heart or Lung Recipients

Outcomes after heart and lung transplants have improved, and many recipients survive long enough to develop secondary renal failure, yet remain healthy enough to undergo kidney transplantation. We used national data reported to United Network for Organ Sharing (UNOS) to evaluate outcomes of 568 kidney after heart (KAH) and 210 kidney after lung (KAL) transplants performed between 1995 and 2008. Median time to kidney transplant was 100.3 months after heart, and 90.2 months after lung transplant. Renal failure was attributed to calcineurin inhibitor toxicity in most patients. Outcomes were compared with primary kidney recipients using matched controls (MC) to account for donor, recipient and graft characteristics. Although 5-year renal graft survival was lower than primary kidney recipients (61% KAH vs. 73.8% MC, p < 0.001; 62.6% KAL vs. 82.9% MC, p < 0.001), death-censored graft survival was comparable (84.9% KAH vs. 88.2% MC, p = 0.1; 87.6% KAL vs. 91.8% MC, p = 0.6). Furthermore, renal transplantation reduced the risk of death compared with dialysis by 43% for KAH and 54% for KAL recipients. Our findings that renal grafts function well and provide survival benefit in KAH and KAL recipients, but are limited in longevity by the general life expectancy of these recipients, might help inform clinical decision-making and allocation in this population.     

Bone graft tuberculosis outbreak in USA: Is it a concern in India?

Globally, 25% of the population is infected with tuberculosis, which poses a leading cause of death worldwide. The transmission of tuberculosis (TB) during organ transplant is reported in the literature whereas only one report has been published on the transmission of TB, during bone allograft transplantation. In the US, in May 2021, an outbreak of TB occurred in patients undergoing spine surgery with bone allograft. This bone graft was retrieved from 80 years deceased donor with latent TB, which was not diagnosed earlier. The recipients were started with a long course of anti-tuberculous drugs. This review narrates the pathway of TB spread among transplant recipients and the strategies to be followed while performing organ or tissue transplantation.     

Understanding renal posttransplantation anemia in the pediatric population

Advances in renal transplantation management have proven to be beneficial in improving graft and patient survival. One of the properties of a well-functioning renal allograft is the secretion of adequate amounts of the hormone erythropoietin to stimulate erythropoiesis. Posttransplantation anemia (PTA) may occur at any point in time following transplantation, and the cause is multifactoral. Much of our understanding of PTA is based on studies of adult transplant recipients. The limited number of studies that have been reported on pediatric renal transplant patients appear to indicate that PTA is prevalent in this patient population. Erythropoietin deficiency or resistance is commonly associated with iron deficiency. An understanding of the risk factors, pathophysiology and management of PTA in the pediatric renal transplant population may provide guidelines for clinicians and researchers in the pursuit of larger prospective randomized control studies aimed at improving our limited knowledge of PTA. Recognition of PTA through regular screening and evaluation of the multiple factors that may contribute to its development are recommended after transplantation.     

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.     

Tuberculosis in southern Chinese renal‐transplant recipients

Abstract: Objectives: To analyze the characteristics of tuberculosis (TB) in Southern Chinese renal transplant recipients, and summarize the corresponding experiences in diagnosis and management. Method: Retrospectively study 41 documented post‐transplant TB cases out of the 2333 patients who received kidney transplantation in the First Affiliated Hospital of Sun Yat‐sen University between Jan. 1991 and Apr. 2007. Results: TB in the post‐renal‐transplant population in Southern China displayed the following characteristics: (i) high incidence within a short time after transplantation, the median interval between renal transplantation and diagnosis of TB was 8 months (range: 1‐156 months) and 56.1% were diagnosed within the first year post‐transplant; (ii) high prevalence (51.2%) of extra‐pulmonary tuberculosis; (iii) high co‐infection rate (19.5%), pathogens included candida albicans, pseudomonas aeruginosa, staphylococcus aureus, Acinetobacter haemolyticus and cytomegalovirus; (iv) fever (82.9%), cough (56.1%) and sputum (39.0%) are the most common clinical manifestations; (v) purified protein derivative of tuberculin (PPD) skin test had little diagnostic value in this group with a negative result in all 41 cases; (vi) acute rejection (29.3%) and liver function damage (17.1%) were the main adverse effects of anti‐tuberculosis chemotherapy; (vii) mortality of patients with post‐transplant tuberculosis reached up to 22.0%. Conclusions: Chinese renal transplant recipients face a high risk of TB because of their immuno‐compromised state and epidemiological prevalence of the disease. Therefore, attention should be given to this differential diagnosis in clinical practice. Balancing the benefits and disadvantages of anti‐tuberculosis chemotherapy is of importance for this specific population.     

Impact of kidney transplantation on the progression of cardiovascular disease

Kidney transplantation, of all the treatment modalities for end-stage renal disease, affords the greatest potential for prolonged survival and improved quality of life. Great strides in immunosuppressant therapy have improved graft survival and forced clinicians to consider other health-care needs of kidney transplant recipients. Chief among these needs is the prevention and treatment of cardiovascular disease. Cardiovascular disease is the most common cause of death among patients with a working renal allograft. Because therapies for primary and secondary prevention are successful in the general population, transplant clinicians are increasingly focused on preventing or limiting the progression of cardiovascular disease. Initiation of aggressive management of conventional atherosclerotic risk factors and uremia-related risk factors, ideally during the early stages of chronic kidney disease (CKD) or after kidney transplantation, and efforts to delay the progression of kidney disease will hopefully reduce the cardiovascular burden in transplant recipients.     

Graft loss and acute coronary syndromes after renal transplantation in the United States

The impact of graft loss on acute coronary syndromes (ACS) after renal transplantation has not been studied in a national population. It was hypothesized that ACS might be more frequent after graft loss, as many of the benefits of a functioning allograft on metabolism and volume regulation would be lost. Data from the 2000 United States Renal Data System (USRDS) was used to conduct an historical cohort study of ACS in 14,237 patients who received renal transplants between April 1, 1995, and June 30, 1998, (followed until April 28, 2000) with valid information from CMS Form 2728, excluding patients with hospitalized ACS before renal transplant. Cox nonproportional regression models were used to calculate the time-dependent adjusted hazard ratio (AHR) of graft loss (censored for death) for time-to-first hospitalization for ACS (International Classification of Diseases 9th Modification Diagnosis Codes [ICD9] code 410.x or 411.x) occurring after transplant. The incidence of ACS was 12.1 per 1000 patient-years (PY) in patients after graft loss versus 6.5 per 1000 PY after transplantation (excluding patients with graft loss). As a time-dependent variable, graft loss had an AHR of 2.54 (95% confidence interval, 1.09 to 5.96; P = 0.031 by Cox regression). Other risk factors associated with ACS included diabetes, older recipient, and male recipient. Allograft rejection was NS. Renal transplant recipients share some of the risk factors for ACS with the general population. In addition, graft loss was identified as a unique risk factor for ACS in this population.     

肾移植术后血脂的变化对移植肾功能的影响

目的:探讨肾移植患者血脂代谢情况及其对移植肾功能的影响。方法:检测89例肾移植患者肾移植前、后的血脂水平,并与移植后1年内发生急性排斥反应及移植后1年时发生慢性移植肾功能不全的患者进行血清肌酐水平相关性分析。结果:与正常对照组比较,肾移植前、后的血清总胆固醇、低密度脂蛋白胆固醇的水平显著升高(P<0.01),甘油三酯、高密度脂蛋白胆固醇、极低密度脂蛋白胆固醇水平无显著差异。血载脂蛋白A1水平显著低于正常对照组(P<0.01)。移植前、后上述血脂水平无显著差异。移植前高胆固醇血症与急性排斥反应的发生存在相关性,高胆固醇血症对慢性移植肾功能不全患者血清肌酐水平升高存在影响。结论:肾移植患者血脂代谢紊乱明显不同于正常人群,高脂血症对急性排斥反应及慢性移植肾功能不全的发生具有不良影响。     

Urologic malignancies in kidney transplantation

With advances in immunosuppression, graft and patient outcomes after kidney transplantation have improved considerably. As a result, long‐term complications of transplantation, such as urologic malignancies, have become increasingly important. Kidney transplant recipients, for example, have a 7‐fold risk of renal cell carcinoma (RCC) and 3‐fold risk of urothelial carcinoma (UC) compared with the general population. While extrapolation of data from the general population suggest that routine cancer screening in transplant recipients would allow for earlier diagnosis and management of these potentially lethal malignancies, currently there is no consensus for posttransplantation RCC or UC screening as supporting data are limited. Further understanding of risk factors, presentation, optimal management of, and screening for urologic malignancies in kidney transplant patients is warranted, and as such, this review will focus on the incidence, surveillance, and treatment of urologic malignancies in kidney transplant recipients.     

Risk of active tuberculosis infection in kidney transplantation recipients: A matched comparative nationwide cohort study

Large-scale evidence comparing the risk of Mycobacterium tuberculosis (TB) between kidney transplant (KT) recipients and dialysis patients is warranted. This is a nationwide retrospective cohort study based on the claims database of South Korea where a moderate prevalence of TB is reported. We included incident KT recipients from 2011 to 2015 and compared their active TB risks with 1:1 matched dialysis and general population control groups, respectively. The risk of incident active TB was assessed by multivariable Cox regression. Associations between active TB and posttransplant death or death-censored graft failure were investigated. The number of matched subjects included in each of the study groups was 7462. The KT group showed a significantly higher risk of active TB than the general population group (hazard ratio [HR] 3.39 [1.88–6.10]), whereas it showed a similar risk to that of the dialysis group (HR 0.98 [0.73–1.31]). In KT patients, active TB was a significant risk factor for both death (HR 2.33 [1.24–4.39]) and death-censored graft failure (HR 2.26 [1.39–3.67]). Although KT recipients may not have to burden the additional risk of active TB when compared with dialysis patients in recent medicine, active TB should not be overlooked as it is associated with a worse prognosis in posttransplant patients.     

Patient survival after renal transplantation: II. The impact of smoking

Renal transplant recipients have significantly higher mortality than individuals without kidney disease and the excess mortality is mainly due to cardiovascular causes. In this study, we sought to determine the impact of smoking, a major cardiovascular risk factor, on patient and renal graft survival. The study population included all adult recipients of first cadaveric kidney transplants done in our institution from 1984 to 1991. By selection, all patients were alive and had a functioning graft for at least 1 yr after transplantation. Smoking history was gathered prior to transplantation. The follow-up period was 84.3 + 41 months and during this time 28%, of the patients died and 21%, lost their graft. By univariate and multivariate analysis, patient survival, censored at the time of graft loss, correlated with these pre-transplant variables: age (p < 0.0001); diabetes (p = 0.0002); history of cigarette smoking (p = 0.004); time on dialysis prior to the transplant (p = 0.0005); and cardiomegaly by chest X-ray (p = 0.0005). Post-transplant variables did not correlate with patient mortality. By Cox regression, patient survival time was significantly shorter in diabetics (p < 0.0001), smokers (p = 0.0005), and recipients older than 40 yr. However, there were no significant differences between the survival of smokers, non-diabetics, diabetics, and older recipients. Patient death was the most common cause of renal transplant failure in smokers, in patients older than 40 yr, and in diabetics, but these patient characteristics did not correlate with graft survival. The prevalence of different causes of death was not significantly different between smokers and non-smokers. In conclusion, a history of cigarette smoking correlates with decreased patient survival after transplantation, and the magnitude of the negative impact of smoking in renal transplant recipients is quantitatively similar to that of diabetes.     

Steroid sparing protocols following nonrenal transplants; the evidence is not there. A systematic review and meta-analysis

We have recently reported that steroid avoidance or withdrawal (SAW) following renal transplantation results in an increase in acute rejection (AR) rates but does not affect graft or patient survival. Cardiovascular risk factors were significantly reduced. It cannot be assumed that the same risks and benefits apply to nonrenal transplants and we have therefore extended this work to evaluate SAW protocols in nonrenal organ transplantation. A detailed literature search identified nine relevant studies; seven in liver, one in cardiac and one in pancreatic transplant recipients. In liver recipients no difference in AR, graft or patient survival was identified. A significant reduction in the risk of new-onset diabetes was observed with SAW, with trends towards benefits in other cardiovascular risk factors, but meta-analysis was hampered by the small number of studies and significant heterogeneity. Some benefits in cardiovascular risk factors were also identified in the cardiac and pancreatic transplant recipients, but again this evidence is of limited quality. Whilst the trend in effect of SAW in nonrenal recipients appears to be similar to that in renal recipients, the lack of robust evidence requires further randomized controlled trials before the true risk/benefit ratio of SAW in nonrenal transplant recipients can be ascertained.