Showing papers in "Clinical Transplantation in 2012"

Complications associated with liver transplantation in the obese recipient

Abstract: The prevalence of the metabolic syndrome with attendant morbid obesity continues to increase nationwide. A concomitant increase in non-alcoholic steatohepatitis (NASH) and associated end-stage liver disease requiring transplantation is expected to parallel this trend. Between January 1, 1997 and December 31, 2008, our center performed 813 solitary adult deceased-donor liver transplants. Patients were divided into groups based on the World Health Organization International Classification of obesity. Patients within each obesity class were compared to normal weight recipients. Preoperative demographics among all groups were similar. NASH was more common in higher BMI groups. Operative time, blood product usage, ICU length of stay, infectious complications, and biliary complications requiring intervention were all higher in obese recipients. Deep venous thrombosis occurred more commonly in patients with Class III obesity. Patients with Class II obesity had lower patient (HR 1.82, CI 1.09-3.01, p=0.02) and allograft survival (HR 1.62, CI 1.02-2.65, p=0.04). Obesity class did not reach statistical significance on multivariate analysis. Despite increased technical operative challenges and medical complexities associated with increasing recipient BMI, morbid obesity in and of itself should not be an absolute contraindication to liver transplantation as these patients have reasonable long-term outcomes.

Factors related to immunosuppressant medication adherence in renal transplant recipients

Abstract: Non-adherence to immunosuppressant medications (ISM) is a significant issue for transplant recipients. This study examines factors influencing ISM adherence in renal transplant recipients (RTRs). Patient-reported data were collected through a cross-sectional survey including use of ISMs, adherence behaviors, perceived adherence barriers, beliefs and attitudes toward ISMs, and patient life satisfaction. Logistic regression was conducted to examine how RTRs' beliefs about use of ISMs, life satisfaction, and ISM adherence barriers were related to adherence. A total of 512 adult commercial insurance enrollees following renal transplantation were included in the analysis. One hundred and seventy-seven RTRs were non-adherent (34.5%); the most frequently cited reason was forgetfulness. RTRs aged 18-29 yr were more likely to be non-adherent than recipients 46-64 yr old (p ≤ 0.001). Non-adherent RTRs had greater adherence barriers than adherent RTRs (p < 0.001). Adherent RTRs believed their ISMs were more necessary than non-adherent RTRs (p < 0.001), while non-adherent RTRs had greater concerns about taking ISMs (p = 0.009) and believed they had less control over their lives than adherent RTRs (p < 0.001). Non-adherent RTRs had lower life satisfaction (p < 0.001). Non-adherence is significantly associated with patients' beliefs about ISMs, perceived barriers, and lower life satisfaction. Strategies to increase ISM adherence are discussed.

Human leukocyte antigen mismatches associated with increased risk of rejection, graft failure, and death independent of initial immunosuppression in renal transplant recipients

Abstract: Human leukocyte antigen (HLA) mismatches have been shown to adversely affect renal allograft outcomes and remain an important component of the allocation of deceased donor (DD) kidneys The ongoing importance of HLA mismatches on transplant outcomes in the era of more potent immunosuppression remains debatable Using Australia and New Zealand Dialysis and Transplant Registry, live and DD renal transplant recipients between 1998 and 2009 were examined The association between the number of HLA mismatches and HLA-loci mismatches and outcomes were examined Of the 8036 renal transplant recipients, 59% had between 2 and 4 HLA mismatches Compared with 0 HLA mismatch, increasing HLA mismatches were associated with a higher risk of graft failure and patient death in the adjusted models HLA mismatches were associated with an incremental risk of rejection although the relative risk was higher for live donor kidney transplants Increasing HLA-AB and HLA-DR mismatches were associated with a greater risk of acute rejection, graft failure, death-censored graft failure, and/or death There was no consistent association between initial immunosuppressive regimen and outcomes Our results corroborate and extend the previous registry analyses demonstrating that HLA mismatches are associated with poorer transplant outcomes independent of immunosuppression and transplant era

Adherence with immunosuppressive treatment after transplantation: results from the French trial PREDICT

Abstract: Although immunosuppressive therapy after organ transplantation is paramount for long-term outcomes, patients do not comply with their immunosuppressive treatment as much as might be expected. In this observational study, patients having undergone a kidney or liver transplantation were enrolled. Adherence was evaluated by patients using the compliance evaluation test and by physicians using a visual analogic scale. A linear regression was performed to identify determinants of adherence. Less patients having undergone kidney transplantation (27%) described themselves as good compliers than liver transplanted patients (40%). Discrepancy was noted between the physician and patient assessments. Rates of good adherence were significantly different depending on gender, age at transplantation, retransplantation, and time elapsed since transplantation, in at least one of the groups evaluated (whole cohort, kidney liver transplantation groups). In all three groups, adherence decreased with the number of immunosuppressants prescribed. In the whole cohort, the rate of good adherence was significantly higher in patients taking lower number of immunosuppressive drugs (45% for 1 vs. 24% for 3 immunosuppressants; p = 0.02). In this study, which is the first study of this scale in France, we confirmed that adherence with immunosuppressant treatment was low and that simpler treatment regimens may favor adherence.

Recurrence of non-alcoholic steatohepatitis and cryptogenic cirrhosis following orthotopic liver transplantation in the context of the metabolic syndrome.

Abstract: Background: Non-alcoholic steatohepatitis (NASH) and cryptogenic cirrhosis (CC) are increasing indications for orthotopic liver transplantation (OLT). The aim of this study is to describe our outcomes and delineate predictors of recurrence of NASH and CC after OLT. Methods: This is a retrospective study from 1996 to 2008. Donor and recipient demographics, metabolic profile, insulin and steroid intake, immunosuppression regimen, operative factors, outcomes, and pathologies were reviewed. Fisher's exact test, Cox regression models, and Kaplan-Meier plots were used. Results: A total of 83 patients were included. Recurrence occurred in 20 patients. Thirty-four percent of the patients with metabolic syndrome (MS) had recurrence of NASH or CC compared with 13% of the patients without MS (p = 0.05). Recurrence also occurred in 32% of the patients with hypertension (HTN) vs. 12% in those without HTN (p = 0.05). Thirty-seven percent of those on insulin had recurrence vs. 6% of those not on insulin (p = 0.05). Five-yr survival probability for patients with MS, HTN, and insulin use was 52%, 61%, and 58%, respectively. Conclusions: Higher recurrence of NASH and CC was associated with presence of MS, HTN and insulin use. Recurrence should be further evaluated in larger studies, with special emphasis on management of MS and prevention strategies.

Patient attitudes toward CDC high infectious risk donor kidney transplantation: inferences from focus groups

Abstract: Ros RL, Kucirka LM, Govindan P, Sarathy H, Montgomery RA, Segev DL. Patient attitudes toward CDC high infectious risk donor kidney transplantation: inferences from focus groups. Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01469.x. © 2011 John Wiley & Sons A/S. Abstract: Introduction: Deceased donors are considered high infectious risk donors (IRDs) based on criteria thought to be associated with risk of HIV transmission. Significant variation exists in provider willingness to utilize IRD kidneys. Little is known about how patients view these organs. Our aim was to explore patient attitudes toward IRDs and IRD kidney transplantation. Methods: Patients were recruited from a single-center deceased donor waitlist. Focus groups stratified by age and race were conducted to ascertain patient attitudes toward IRD kidney transplantation. Transcripts were examined using standard qualitative methods. Results: Patients considered IRD kidneys most appropriate for patients at high risk of death or with poor quality of life on dialysis. Patients felt unprepared to receive organ offers, especially from IRDs. They desired information about IRD behaviors, kidney quality, and probability of undetected infection. Patients weighed the opinion of their nephrologist most heavily when deciding about organ offers. A brief education session about donor screening resulted in increased willingness to consider IRD kidneys. Conclusions: Lack of preparedness contributes to patient apprehension toward IRD organs. Ongoing transplant education seems necessary. The non-transplant nephrologist seems to be the most trusted source of information.

Immunosuppressant treatment adherence, barriers to adherence and quality of life in renal and liver transplant recipients in Spain.

Abstract: Morales JM, Varo E, Lazaro P. Immunosuppressant treatment adherence, barriers to adherence and quality of life in renal and liver transplant recipients in Spain. Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01544.x. © 2011 John Wiley & Sons A/S. Abstract: To assess the adherence to immunosuppressant therapy (IST) and perceived barriers affecting IST adherence and quality of life (QOL) in patients who had received a renal (RT) or liver transplant (LT), a questionnaire was sent to over 9000 RT and LT recipients in Spain. Questionnaire comprised questions about patient’s socio-demographic, organ transplant and medication characteristics; IST adherence and patient’s perceived barriers to adherence; and patient’s QOL using the EuroQol. Data from 1983 RT patients and 1479 LT patients were analyzed. Self-reported adherence to IST in RT (92.6%) and LT (88.5%) recipients was high. Daily medication intake (mean of 2–3 doses/d per patient) was considered a lifestyle restriction in about 25% of transplant recipients and was the most common barrier to adherence perceived by over 30% of RT and LT patients. Overall, high-intensity treatment regimens were associated with poorer QOL (EuroQol <70) compared with low-intensity treatment regimens. Most RT (71.0%) and LT (61.4%) patients would prefer to suppress the evening dose if they were able to. Although high adherence rates to IST were reported in this first large Spanish survey in RT and LT patients, adjustment of daily treatment intensity by less frequent dosing may be an adequate strategy to minimize barriers to adherence and improve QOL.

Combination of biological and morphological parameters for the selection of patients with hepatocellular carcinoma waiting for liver transplantation

Abstract: Lai Q, Avolio AW, Manzia TM, Sorge R, Agnes S, Tisone G, Berloco PB, Rossi M. Combination of biological and morphological parameters for the selection of patients with hepatocellular carcinoma waiting for liver transplantation. Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01572.x. © 2011 John Wiley & Sons A/S. Abstract: Background: In the last several years, there has been no agreement on how to possibly expand the Milan criteria (MC) in the selection of patients with hepatocellular carcinoma (HCC) for listing for liver transplant (LT). The aim of the study is to evaluate morphological and biological tumor parameters to identify new expanded criteria for the selection of patients with HCC as candidates for LT. Methods: We retrospectively analyzed 158 consecutive patients with HCC who underwent LT. Results: Twelve (7.6%) recurrences were observed. At multivariate analysis, alpha-fetoprotein (AFP) >400 ng/mL (odds ratio [OR] 8.4, p 8 cm (OR 7.4, p = 0.01) were the strongest predictors for recurrence. AFP-TTD criteria resulted in a low five-yr recurrence rate (4.9%) and an increased number of LT compared with the MC (22.2% increase). The five-yr disease-free survival rate was 74.4% in AFP-TTD criteria in patients, with a higher effectiveness in stratifying the cohort with respect to the MC. Conclusions: Both AFP and TTD are good independent predictors of HCC recurrence. Their combination appears to obtain a better selection of candidates for LT without worsening patient survival and recurrence rates. This approach allows for an increase in the number of potentially transplantable patients.

The role of Thymoglobulin induction in kidney transplantation: an update

Abstract: The rabbit antithymocyte globulin Thymoglobulin first became available over 25 yr ago and is the most widely used lymphocyte-depleting preparation in solid organ transplantation. Thymoglobulin targets a wide range of T-cell surface antigens as well as natural killer-cell antigens, B-cell antigens, plasma cell antigens, adhesion molecules and chemokine receptors, resulting in profound, long-lasting T-cell depletion. Randomized studies have established the anti-rejection efficacy of Thymoglobulin in kidney transplantation. Experimental and clinical data suggest that Thymoglobulin administration may ameliorate ischemia reperfusion injury, thus reducing the incidence of delayed graft function (DGF). Studies have demonstrated the benefit of using Thymoglobulin to facilitate immunosuppression minimization, both for corticosteroid and calcineurin inhibitor (CNI) withdrawal or avoidance, with potential improvement in cardiovascular and renal outcomes. The optimal cumulative dose for Thymoglobulin induction is 6-7.5 mg/kg, with vigilant short- and long-term monitoring of hematological status. Induction with Thymoglobulin is now indicated in immunologically high-risk patients, in those at increased risk of DGF and to maintain efficacy in low-risk transplant recipients receiving steroid or CNI minimization or avoidance regimens. We suggest that in future trials Thymoglobulin be tested with costimulation signal blockers and other immunosuppressants with the objective of establishing operational tolerance.

Self-reported non-adherence to immune-suppressant therapy in liver transplant recipients: demographic, interpersonal, and intrapersonal factors.

Abstract: Lamba S, Nagurka R, Desai KK, Chun SJ, Holland B, Koneru B. Self-reported non-adherence to immune-suppressant therapy in liver transplant recipients: demographic, interpersonal, and intrapersonal factors. Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01489.x. © 2011 John Wiley & Sons A/S. Abstract: Adherence to immune suppressants and follow-up care regimen is important in achieving optimal long-term outcomes after organ transplantation. To identify patients most at risk for non-adherence, this cross-sectional, descriptive study explores the prevalence and correlates of non-adherence to immune-suppressant therapy among liver recipients. Anonymous questionnaires mailed consisted of the domains: (i) adherence barriers to immune suppressants, (ii) immune suppressants knowledge, (iii) demographics, (iv) social support, (v) medical co-morbidities, and (vi) healthcare locus of control and other beliefs. Overall response was 49% (281/572). Data analyzed for those transplanted within 10 yr of study reveal 50% (119/237) recipients or 9.2/100 person years reporting non-adherence. Non-adherence was reported highest in the 2–5 yr post-transplant phase (69/123, 56%). The highest immune-suppressant non-adherence rates were in recipients who are: divorced (26/34, 76%, p = 0.0093), have a history of substance or alcohol use (42/69, 61%, p = 0.0354), have mental health needs (50/84, 60%, p = 0.0336), those who missed clinic appointments (25/30, 83%, p < 0.0001), and did not maintain medication logs (71/122, 58%, p = 0.0168). Respondents who were non-adherent with physician appointments were more than four and a half times as likely (OR 4.7, 95% CI 1.5–14.7, p = 0.008) to be non-adherent with immune suppressants. In conclusion, half of our respondents report non-adherence to immune suppressants. Factors identified may assist clinicians to gauge patients’ non-adherence risk and target resources.

Prevalence of gastroparesis before and after lung transplantation and its association with lung allograft outcomes.

Abstract: The main cause of late morbidity and mortality after lung transplantation is bronchiolitis obliterans syndrome (BOS). This study assesses the prevalence of gastroparesis among lung-transplant recipients and its association with BOS. The files of 139 patients who underwent nuclear gastric emptying studies before and/or three and 12 months after lung transplantation were reviewed, and the correlation of gastric emptying time (GET) at each time point with the occurrence of acute rejection or BOS (stage 0p or higher) was evaluated. Delayed gastric emptying (DGE; t(1/2) > 90 min) was documented in 50% of patients before transplantation - 74% at three months and 63% at 12 months. Median pre-transplant t(1/2) was 108 min in patients who acquired BOS and 77 min in BOS-free patients (p = 0.022). Among patients with pre-transplant DGE, 58% were BOS-free at 24 months post-operatively and 37% at 36 months; corresponding rates in patients with normal motility were 78% and 63% (p = 0.084). On multiple regression analysis adjusting for other measures of upper gastrointestinal dysfunction, GET before or three months after transplantation was significantly associated with BOS (OR 1.05 [95% CI 1.01-1.09] and OR 1.001 [1.001-1.005] per minute t(1/2)). Gastroparesis is common in lung-transplant recipients and associated with the development of BOS.

Superiority of virtual microscopy versus light microscopy in transplantation pathology.

Abstract: Ozluk Y, Blanco PL, Mengel M, Solez K, Halloran PF, Sis B. Superiority of virtual microscopy versus light microscopy in transplantation pathology. Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01506.x. © 2011 John Wiley & Sons A/S. Abstract: Virtual microscopy has begun to change conventional pathology practice. We tested the reliability of this new technology in transplantation pathology. We studied 40 kidney transplant biopsies for cause and compared reproducibility of Banff scores using virtual slides versus glass slides. Three glass slides per biopsy were scanned as high-resolution digital slides using Aperio ScanScope. Three pathologists independently reviewed the biopsies: twice by glass slides and twice by virtual slides. Eleven histopathological lesions were scored and used to construct diagnosis according to Banff criteria. The intra-observer reproducibility of Banff scores was substantially good using either virtual slides or glass slides (mean κ: 0.69 vs. 0.64, p > 0.05). The inter-observer reproducibility of Banff scores was better in virtual slides than in glass slides (mean κ: 0.42 vs. 0.28, p < 0.001). Among the lesions, transplant glomerulopathy scoring by virtual slides showed the highest inter-observer reproducibility, with a similar accuracy to glass slides. The agreement for acute rejection between virtual and glass slides was not different from the agreement between two readings of glass slides. Thus, virtual microscopy is a reliable and more reproducible technology and has several advantages over glass slides, e.g., accessibility via internet, no fading. We recommend virtual microscopy for transplant diagnostics, including utilization for clinical trials.

Prevention of relapse using DLI can increase survival following HLA-identical transplantation in patients with advanced-stage acute leukemia: a multi-center study.

Abstract: A total of 123 consecutive patients with advanced-stage, acute leukemia undergoing HSCT from HLA-identical sibling donors were analyzed. A G-CSF-primed DLI was planned within day 60 post-transplantation before hematologic relapse was diagnosed. Fifty of the 123 individuals received prophylactic DLI, and 73 individuals received no prophylactic treatment. The incidence of grades II-IV acute graft-versus-host disease (GVHD) was 17% for patients receiving DLI and 23% for patients not receiving DLI (p = 0.35). The incidence of chronic GVHD was 38% for patients receiving DLI and 17% for patients not receiving DLI (p = 0.021). The two-yr cumulative incidence of relapse was significantly lower in patients who received prophylactic DLI (46%) compared with patients who did not receive prophylactic DLI (66%) (p = 0.02). The three-yr probability of overall survival was higher in patients who received prophylactic DLI (36%) than in patients who did not receive prophylactic DLI (11%) (p = 0.001). The leukemia-free survival was also higher in patients who received prophylactic DLI (29%) than in patients who did not receive prophylactic DLI (9%) (p = 0.001). Our comparisons suggest that the prophylactic use of DLI can significantly increase survival of patients with advanced-stage, acute leukemia who receive HLA-identical sibling HSCT.

Estimating the risks of acquiring a kidney abroad: a meta‐analysis of complications following participation in transplant tourism

Abstract: A meta-analysis of odds ratios comparing the risks of participating in transplant tourism by acquiring a kidney abroad to the risks associated with domestic kidney transplant was undertaken. Comparison across 12 medical outcomes indicates transplant tourists are significantly more likely to contract cytomegalovirus, hepatitis B, HIV, post-transplantation diabetes mellitus, and wound infection than those receiving domestic kidney transplant. Results also indicate that domestic kidney transplant recipients experience significantly higher one-yr patient- and graft-survival rates. Analyses are supplemented by independent comparisons of outcomes and provide practitioners with weighted estimates of the proportion of transplant recipients experiencing 15 medical outcomes. Practitioners are encouraged to caution patients of the medical risks associated with transplant tourism. Despite the illegal and unethical nature of transplant tourism, additional efforts are indicated to eliminate the organ trade and to educate wait-listed patients about the risks of transplant tourism.

Acute kidney injury as defined by the RIFLE criteria is a risk factor for kidney transplant graft failure

Abstract: Acute kidney injury (AKI) is not recognized as a major complication at the maintenance phase after kidney transplantation (KTx). Moreover, it is not clear whether the onset of AKI leads to graft failure. We examined the incidence of AKI that developed three months or later after KTx at our institute. We examined whether the incidence of AKI defined by the Risk of renal dysfunction, Injury to the kidney, Failure of kidney function, Loss of kidney function and End-stage kidney disease criteria associates with graft failure by matched-pair Cox regression analysis. A total of 289 patients were available for the final analysis. The overall incidence of AKI was 20.4%, and the common etiology of AKI was bacterial infectious diseases. The group that developed AKI had significantly lower graft survival than non-AKI group independently of acute rejection. AKI Risk represented a high risk for graft failure and AKI Injury/Failure represented a higher risk for graft failure. The analysis by the AKIN classification yielded the similar results. These results indicate that AKI is a relatively common complication of KTx and represents the major risk for graft failure. We should make every effort in the prevention and early detection to avoid the occurrence of AKI and the subsequent graft failure after KTx.

Renal allograft loss in the first post‐operative month: causes and consequences

Abstract: Early transplant failure is a devastating outcome after kidney transplantation. We report the causes and consequences of deceased donor renal transplant failure in the first 30 d at our center between January 1990 and December 2009. Controls were adult deceased donor transplant patients in the same period with an allograft that functioned >30 d. The incidence of early graft failure in our series of 2381 consecutive deceased donor transplants was 4.6% (n = 109). The causes of failure were allograft thrombosis (n = 48; 44%), acute rejection (n = 19; 17.4%), death with a functioning allograft (n = 17; 15.6%), primary non-function (n = 14;12.8%), and other causes (n = 11; 10.1%). Mean time to allograft failure was 7.3 d. There has been a decreased incidence of all-cause early failure from 7% in 1990 to 30 d (p < 0.001). Early allograft failure was strongly associated with reduced patient survival (p < 0.001). In conclusion, early renal allograft failure is associated with a survival disadvantage, but has thankfully become less common in recent years.

Incidence and predictors of post‐reperfusion syndrome in living donor liver transplantation

Abstract: A characteristic pattern of hemodynamic changes that may occur in reperfusion phase of liver transplantation (LT) is known as post-reperfusion syndrome (PRS). In this study, we determined the frequency of PRS and evaluated possible predictors of PRS. The medical records of 152 patients who underwent living donor LT were reviewed. PRS was defined as a decrease in mean arterial pressure of more than 30% from the baseline value for more than one min during the first five min after reperfusion. The frequency of PRS was determined, and patients were divided into two groups: PRS group and non-PRS group. Donor factors, preoperative and intraoperative recipient factors, and postoperative outcomes were compared between the two groups. PRS occurred in 58 recipients (34.2%). Preoperative model for end-stage liver disease scores of recipients and percentage of graft steatotic changes were higher in PRS group. PRS group showed higher heart rates and lower hemoglobin values preoperatively. Before reperfusion, PRS group received more transfusion and their urine output was less than that of non-PRS group. Postoperatively, peak bilirubin during the first five d after LT was higher in PRS group. In conclusion, both severity of liver disease and graft steatosis may increase risk for PRS in LT. Further prospective studies of PRS in its relationship to outcome are indicated.

Quantitative Epstein–Barr virus shedding and its correlation with the risk of post‐transplant lymphoproliferative disorder

Abstract: We postulated that quantitative monitoring of Epstein-Barr virus (EBV) shedding after transplantation could distinguish EBV-associated illnesses and predict clinical outcome. EBV DNA was measured in solid organ (SOT) and hematopoietic cell transplants (HCT) using our own real-time TaqMan EBV PCR. The proportion of patients who had EBV DNAemia post-transplant was significantly lower in HCT vs. SOT (p 10(5) (p < 0.001). EBV PCR was predictive in 29 (78%) of 37 patients tested within three wk prior to tissue diagnosis of PTLD, and thus, we conclude that EBV PCR with careful attention paid to changes in EBV DNAemia could lead to earlier diagnosis and treatment of PTLD.

Stress and coping in caregivers of patients awaiting solid organ transplantation

Abstract: Caregivers for patients undergoing solid organ transplantation play an essential role in the process of transplantation. However, little is known about stress and coping among these caregivers. Six hundred and twenty-one primary caregivers of potential candidates for lung (n = 317), liver (n = 147), heart (n = 115), and/or kidney (n = 42) transplantation completed a psychometric test battery at the time of the candidate's initial pre-transplant psychosocial evaluation. Caregivers were generally well adjusted, with only 17% exhibiting clinical symptoms of depression (Beck Depression Inventory-II score >13) and 13% reporting clinical levels of anxiety (State Trait Anxiety Inventory score >48). Greater caregiver burden and negative coping styles were associated with higher levels of depression. Greater objective burden and avoidant coping were associated with higher levels of anxiety. Caregivers evidenced a high degree of socially desirable (i.e., defensive) responding, which may reflect a deliberate effort to minimize fears or worries so as to not jeopardize patients' listing status.

Effect of education on racial disparities in access to kidney transplantation.

Abstract: Higher education level might result in reduced disparities in access to renal transplantation. We analyzed two outcomes: (i) being placed on the waiting list or transplanted without listing and (ii) transplantation in patients who were placed on the waiting list. We identified 3224 adult patients with end-stage renal disease (ESRD) in United States Renal Data System with education information available (mean age of ESRD onset of 57.1 ± 16.2 yr old, 54.3% men, 64.2% white, and 50.4% diabetics). Compared to whites, fewer African Americans graduated from college (10% vs. 16.7%) and a higher percentage never graduated from the high school (38.6% vs. 30.8%). African American race was associated with reduced access to transplantation (hazard ratio [HR] 0.70, p < 0.001 for wait-listing/transplantation without listing; HR 0.58, p < 0.001 for transplantation after listing). African American patients were less likely to be wait-listed/transplanted in the three less-educated groups: HR 0.67 (p = 0.005) for those never completed high school, HR 0.76 (p = 0.02) for high school graduates, and HR 0.65 (p = 0.003) for those with partial college education. However, the difference lost statistical significance in those who completed college education (HR 0.75, p = 0.1). In conclusion, in comparing white and African American candidates, racial disparities in access to kidney transplantation do exist. However, they might be alleviated in highly educated individuals.

Extracorporeal life support as a bridge to high‐urgency heart transplantation

Abstract: Barth E, Durand M, Heylbroeck C, Rossi-Blancher M, Boignard A, Vanzetto G, Albaladejo P, Chavanon O. Extracorporeal life support as a bridge to high-urgency heart transplantation. Clin Transplant 2011 DOI: 10.1111/j.1399-0012.2011.01525.x. © 2011 John Wiley & Sons A/S. Abstract: Extracorporeal life support (ECLS) represents an effective, emergent therapy for patients with end-stage heart failure or cardiac arrest. However, ECLS is typically not used as a bridge to heart transplantation because of the limited duration of ECLS. In France, high-urgency priority heart transplantation remains a possibility for transplant patients who are on ECLS. In this article, we present our experience with high-urgency priority heart transplantation after ECLS. From July 2004 to December 2009, 242 patients underwent emergent ECLS. Heart transplantation was performed in eight of these patients. Time of ECLS was 6.3 ± 4.6 d. Before heart transplantation, all patients on ECLS had decreased organ dysfunctions and four were conscious. Despite frequent post-operative complications, no death occurred during the first year after transplantation. In our experience, ECLS is a valid method of supporting patients awaiting high-urgency heart transplantation and can be used as a short-term bridge to heart transplantation.

Factors associated with the development of cardiac allograft vasculopathy--a systematic review of observational studies.

Abstract: Cardiac allograft vasculopathy (CAV) is a significant factor impacting outcomes after heart transplant. We performed a systematic review of risk factors for the development of CAV. A search of electronic databases was performed. The eligibility criteria included cohort and case-control studies with more than 50 adult patients submitted to a heart transplant. The outcome should be CAV diagnosed by angiography and/or intravascular ultrasound (IVUS). Two reviewers performed study selection, data abstraction, and quality assessment. Of 2514 citations, 66 articles were included--46 had 200 participants or less; 61 were single-center; and 44 were retrospective cohorts. The most used definition of CAV using angiography was the detection of any degree of abnormality (21 studies of 58). In studies using IVUS, an intimal thickness ≥0.5 mm was the most used definition (five of eight studies). Quality assessment revealed an inadequate description of patient selection, attrition, and accounting of potential confounders. Donor age, recipient age, recipient gender, etiology of heart failure, ischemic time, human leukocyte antigen matching, cytomegalovirus, lipid profile, and rejection episodes were the most studied factors. Our review indicates that the current evidence is not consistent across different studies. The definite contribution of risk factors for the development of CAV is still to be determined.

Inadequacy of cardiovascular risk factor management in chronic kidney transplantation - evidence from the FAVORIT study.

Abstract: Background Kidney transplant recipients (KTRs) have increased risk of cardiovascular disease (CVD). Our objective is to describe the prevalence of CVD risk factors applying standard criteria and use of CVD risk factor–lowering medications in contemporary KTRs. Methods The Folic Acid for Vascular Outcome Reduction in Transplantation study enrolled and collected medication data on 4107 KTRs with elevated homocysteine and stable graft function an average of five yr post-transplant. Results CVD risk factors were common (hypertension or use of blood pressure (BP) lowering medication in 92%, borderline or elevated low-density lipoprotein (LDL) or use of lipid-lowering agent in 66%, history of diabetes mellitus in 41%, and obesity in 38%); prevalent CVD was reported in 20% of study participants. National Kidney Foundation BP guidelines (BP <130/80 mmHg) were not met by 69% of participants. Uncontrolled hypertension (BP of 140/90 mmHg or higher) was present in 44% of those taking antihypertension medication; 18% of participants had borderline or elevated LDL, of which 60% were untreated, and 31% of the participants with prevalent CVD were not using an antiplatelet agent. Conclusion There is opportunity to improve treatment and control of traditional CVD risk factors in kidney transplant recipients.

A health economic analysis of clinical islet transplantation.

Abstract: Islet cell transplantation is in clinical development for type 1 diabetes. There are no data on the cost in relationship to its benefits. We performed a cost-effectiveness analysis and made a comparison with standard insulin therapy, using Markov modeling and Monte Carlo simulations. The patient population was adults aged 20 yr suffering from hypoglycemia unawareness. Data were estimates from literature and clinical trials: costs were based on the situation in the United States. For insulin therapy, cumulative cost per patient during a 20-yr follow-up was $663,000, and cumulative effectiveness was 9.3 quality-adjusted life years (QALY), the average cost-effectiveness ratio being $71,000 per QALY. Islet transplantation had a cumulative cost of $519,000, a cumulative effectiveness of 10.9 QALY, and an average cost-effectiveness ratio of $47,800. During the first 10 yr, costs for transplantation were higher, but cumulative effectiveness was higher from the start onwards. In sensitivity analyses, the need for one instead of two transplants during the first year did not affect the conclusions, and islet transplantation remained cost-saving up to an initial cost of the procedure of $240,000. This exploratory evaluation shows that islet cell transplantation is more effective than standard insulin treatment, and becomes cost-saving at about 9-10 yr after transplantation.

Liver transplantation in the MELD era--analysis of the OPTN/UNOS registry.

Abstract: OVERVIEW OF THE MODEL FOR END-STAGE LIVER DISEASE (MELD): MELD has been successful in its initial aim of reducing pre-transplant mortality by better organ allocation; at the same time, it generated a new challenge of achieving better posttransplant outcomes by adjusting the hierarchy of allocation to sicker patients. Our analysis of 49,867 adult patients in the MELD era (2002 through 2011) showed a change in the dynamics of the transplant population: the number of patients with higher priority (MELD-exception patients and high-MELD patients) has been progressively increasing while the number of those without priority has remained constant or has been decreasing depending on their disease. The re-transplantation rate has been increasing for high-MELD patients. An increase in number has also observed of major racial groups other than Whites. Overall graft survival-including that for re-transplant-has improved, regardless of MELD levels, during the decade since MELD implementation in 2002. 2. MELD WITH PRIMARY DISEASES: Over the past two decades, the incidence of hepatitis C virus (HCV) has been increasing, and after the inception of MELD, hepatocellular carcinoma (HCC) and non-alcoholic liver disease (NASH) have been progressively increasing. There appears to be a general tendency toward lower graft survival in high-MELD patients in both deceased- and living-donor transplantation. However, this trend differed among the 12 primary diseases, in which significantly lower graft survival was observed in high-MELD patients with alcoholic liver disease (ALD), NASH, autoimmune disorders (AI), HCV, hepatitis B virus (HBV) or non-HCC cancers. Overall, HCV seropositive patients had lower graft survival than HCV seronegative patients. This was also true in each high- and low-MELD group. However, analysis of the primary diseases showed four patterns for the impact of HCV seropositivity related to MELD levels: lower graft survival with anti-HCV regardless of MELD level (with acute hepatic failure, metabolic disorders and HBV); no correlation between the impact of HCV antibodies and MELD levels (with primary biliary cirrhosis [PBC], primary sclerosing cholangitis [PSC] and HCC); lowest graft survival with high MELD scores in the presence of HCV antibodies (with AI, ALD and NASH); and worse survival without HCV (non-HCC cancers). 3. MELD EXCEPTION: Among the primary diseases, the five with a high rate of HCC exception (> 70%) were HCC, HCV, HBV, ALD and AI; the four with a high rate of non-HCC exception (> 60%) were non-HCC cancers, PSC, PBC, and "Others." HCC patients with HCC-exception appear to have derived a greater benefit from transplantation, with better graft survival, than HCC patients without exception. The same beneficial effect of non-HCC exception has been observed with non-HCC cancers, the majority of them cholangiocarcinoma.

Influence of liver-disease etiology on long-term quality of life and employment after liver transplantation

Abstract: The etiology of liver disease would expectedly affect health-related quality of life (HRQoL) and employment after liver transplantation (LT), but studies are scarce. We sent the 15D HRQoL instrument and an employment questionnaire to all 401 adult LT patients alive in Finland in 2007. The response rate was 89% (n = 353; mean of eight yr since LT). In age-adjusted analysis, patients transplanted for primary sclerosing cholangitis (PSC; n = 56), primary biliary cirrhosis (PBC; n = 72), acute liver failure (ALF; n = 76), alcoholic cirrhosis (n = 38), or liver tumor (n = 22) exhibited comparable HRQoL, whereas the combined group of miscellaneous chronic liver diseases (n = 89) exhibited significantly higher HRQoL scores (p = 0.003). Among working-aged patients (20-65 yr at LT), employment rates were highest in the PSC (56%) group and lowest in the ALF (39%) and PBC (29%) groups. In age-adjusted logistic regression, patients with PSC or alcoholic cirrhotics were 2.4- and 2.5-fold more likely to resume work after LT than patients with PBC. In conclusion, HRQoL scores late after LT were in general relatively high and comparable among disease groups. Patients with PSC or alcoholic cirrhosis were most likely to resume work after LT. The relatively low employment among patients with ALF may merit enhanced rehabilitation efforts.

Impact of neoadjuvant transarterial chemoembolization on tumor recurrence and patient survival after liver transplantation for hepatocellular carcinoma: a retrospective analysis.

Abstract: Transarterial chemoembolization (TACE) has gained wide acceptance as a bridge to liver transplantation (LT) in patients with hepatocellular carcinoma (HCC). Aim of this analysis was to compare long-term results with and without neoadjuvant TACE and to identify subgroups, which particularly benefit from TACE. Patients with HCC transplanted at our center were retrospectively analyzed. The following were excluded to increase consistency: incidental-HCC, Child-C, living-related-LT, other HCC-specific-treatment. Of 336 patients, 177 were subject of this analysis, 71 received TACE and 106 no HCC therapy. Patients with and without TACE showed similar five-yr survival (73/67%) and recurrence rates (23/29%). Progression on the waiting list was associated with a higher recurrence rate in the TACE (50 vs.12%) and the non-TACE group (40 vs. 22%). HCC recurrence was reduced in patients inside Milan (0.053) and UCSF (0.037) criteria by neoadjuvant TACE but not outside UCSF (0.99). Also a trend towards an improved survival was seen within these criteria. Our large single center experience suggests that TACE lowers the HCC recurrence rate in patients inside the Milan and UCSF criteria. Moreover, the response to TACE is a good indicator of low recurrence rates. The effect of TACE might be more pronounced in patients with longer waiting time than in this cohort (mean, 4.6 months).

The impact of hepatitis C virus donor and recipient status on long‐term kidney transplant outcomes: University of Wisconsin experience

Abstract: The survival benefit of transplanting hepatitis C (HCV)-positive donor kidneys into HCV-positive recipients remains uncertain. The purpose of this study was to assess the effect of HCV-status of the donor (D) kidney on the long-term outcomes in kidney transplant recipients (R). We evaluated 2169 consecutive recipients of deceased-donor kidney transplants performed between 1991 and 2007. The following HCV cohorts were identified: D-/R- (n = 1897), D-/R+ (n = 59), D+/R- (n = 118), and D+/R+ (n = 95). Patients were followed for a mean of 6.02 (standard deviation = 4.26) yr. In a mulitvariable Cox-proportional hazards model, D+/R+ cohort had significantly lower patient survival (adjusted-hazard ratio [HR] 2.1, 95% CI [1.4-2.9]) with respect to the reference D-/R- group, whereas mortality was not increased in D-/R+ group. The rate of graft loss was increased in both D+/R+ and D-/R+ but was comparable with each other (adjusted-HR 1.8, 95% CI [1.4-2.5]) vs. adjusted-HR 2.0, 95% CI [1.4-2.8], respectively). D-/R+ cohort experienced significantly higher rate of rejection (adjusted-HR 1.7, 95% CI [1.2-2.5]) and chronic allograft nephropathy (adjusted-HR 2.1, 95% CI [1.2-3.7]). Neither donor nor recipient HCV-status impacted the risk of recurrent or de novo GN. Transplanting HCV-positive kidneys as opposed to HCV-negative kidneys into HCV-positive recipients provided similar graft survival but compromised patient survival in the long term.

De novo food sensitization and eosinophilic gastrointestinal disease in children post-liver transplantation.

Abstract: Background Children have increased prevalence of food allergy (FA) and eosinophilic gastrointestinal disease (EGID) following liver transplantation. The aim of this study was to identify related risk factors. Methods Chart review of pediatric liver transplant (LT) recipients with de novo FA and/or EGID post-LT and non-allergic controls. Results We identified 30 (8.5%) children with FA and/or EGID among 352 pediatric LT recipients. Median age at transplant was 0.9 inter-quartile range (IQR 0.6–2.0) years. FA developed at a median 1.0 (IQR 0.5–8.2) yr post-LT and manifested with gastrointestinal symptoms (53%) or urticaria/angioedema (40%). Commonly avoided foods included milk (60%), egg (57%), and peanut (47%). Of the 15 children with FA who underwent endoscopy, 11 had eosinophilic infiltrates in multiple segments of the esophagus alone or in combination with other bowel segments. FA and EGID were linked to transplantation at a younger age (median, 0.9 vs. 5.5 yr), higher frequency of blood eosinophilia, and prior history of rhinitis and atopic dermatitis. Tacrolimus use and tacrolimus serum levels were similar between allergic subjects and controls. Conclusions Findings suggest that exposure to tacrolimus alone post-LT is insufficient to initiate de novo allergic disease in LT recipients; rather, younger age and underlying predisposition to atopic disease may play larger roles.

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

Abstract: 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-naive 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-naive 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.