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Allograft Dysfunction (allograft + dysfunction)
Kinds of Allograft Dysfunction Selected AbstractsImmunobiology of Chronic Lung Allograft Dysfunction: New Insights from the Bench and BeyondAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009R. A. Shilling The first successful human lung transplants were performed in the 1980s. Since that time lung transplantation has been a therapeutic modality for end-stage pulmonary diseases. However, chronic rejection, known as obliterative bronchiolitis (OB)/bronchiolitis obliterans syndrome (BOS), is the key reason why the 5-year survival is only 50%, which is significantly worse than most other solid organ transplants. Recent studies have provided exciting advances that are beginning to be translated into findings in humans. This review will highlight the current advances in understanding the mechanisms of OB/BOS in lung transplant recipients. [source] Monocyte Infiltration and Kidney Allograft Dysfunction During Acute RejectionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2008R. Girlanda Multiple cell types infiltrate acutely rejecting renal allografts. Typically, monocytes and T cells predominate. Although T cells are known to be required for acute rejection, the degree to which monocytes influence this process remains incompletely defined. Specifically, it has not been established to what degree monocytes impact the clinical phenotype of rejection or how their influence compares to that of T cells. We therefore investigated the relative impact of T cells and monocytes by correlating their presence as measured by immunohistochemical staining with the magnitude of the acute change in renal function at the time of biopsy in 78 consecutive patients with histological acute rejection. We found that functional impairment was strongly associated with the degree of overall cellular infiltration as scored using Banff criteria. However, when cell types were considered, monocyte infiltration was quantitatively associated with renal dysfunction while T-cell infiltration was not. Similarly, renal tubular stress, as indicated by HLA-DR expression, increased with monocyte but not T-cell infiltration. These data suggest that acute allograft dysfunction is most closely related to monocyte infiltration and that isolated T-cell infiltration has less acute functional impact. This relationship may be useful in assigning acute clinical relevance to biopsy findings. [source] Impact of Cyclosporine Reduction With MMF: A Randomized Trial in Chronic Allograft Dysfunction.AMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2006Reference' Study Long-term use of calcineurine inhibitors (CNIs) may contribute to the development of chronic allograft dysfunction (CAD). We investigate the impact of the introduction of MMF combined with cyclosporine (CsA) 50% dose reduction. An open, randomized, controlled, multicenter, prospective study was conducted in 103 patients, receiving a CsA-based therapy with a serum creatinine between 1.7,3.4 mg/dL, more than 1 year after transplantation. They were randomized to receive MMF with half dose of CsA (MMF group) or to continue their maintenance CsA dose (control group). A total of 96 weeks after randomization, the evolution of renal function assessed by regression line analysis of 1/SeCr improved in the MMF group (positive slope) vs. the control group (negative slope), 4.2 × 10,4 vs. ,3.0 × 10,4, respectively (p < 0.001). Concurrently, the absolute renal function improved significantly in the MMF group. No episode of biopsy-proven acute rejection occurred. One patient in each group lost his graft because of biopsy-proven chronic allograft nephropathy. There was a significant decrease of triglycerides level in the MMF group. Anemia and diarrhea were statistically more frequent in the MMF group. In CAD, the reduction of CsA in the presence of MMF results in significant improvement in renal function during a 2-year follow-up. [source] Correlation of Donor-Specific Antibodies, Complement and Its Regulators with Graft Dysfunction in Cardiac Antibody-Mediated RejectionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009C. D. Tan Antibody-mediated rejection (AMR) is an immunopathologic process in which activation of complement often results in allograft injury. This study correlates C4d and C3d with HLA serology and graft function as diagnostic criteria for AMR. Immunofluorescence staining for C4d and C3d was performed on 1511 biopsies from 330 patients as part of routine diagnostic work-up of rejection. Donor-specific antibodies were detected in 95% of those with C4d+C3d+ biopsies versus 35% in the C4d+C3d, group (p = 0.002). Allograft dysfunction was present in 84% in the C4d+ C3d+ group versus 5% in the C4d+C3d, group (p < 0.0001). Combined C4d and C3d positivity had a sensitivity of 100% and specificity of 99% for the pathologic diagnosis of AMR and a mortality of 37%. Since activation of complement does not always result in allograft dysfunction, we correlated the expression pattern of the complement regulators CD55 and CD59 in patients with and without complement deposition. The proportion of patients with CD55 and/or CD59 staining was highest in C4d+C3d, patients without allograft dysfunction (p = 0.03). We conclude that a panel of C4d and C3d is diagnostically more useful than C4d alone in the evaluation of AMR. CD55 and CD59 may play a protective role in patients with evidence of complement activation. [source] Prospective study of urine cytology screening for BK polyoma virus replication in renal transplant recipientsCYTOPATHOLOGY, Issue 6 2008M. Koukoulaki Objective:, BK virus (BKV) may be associated with interstitial nephritis in renal transplant recipients and this can lead to irreversible chronic allograft dysfunction. Early diagnosis of BKV nephropathy determines its progress because no specific antiviral therapy exists. Urine cytology, detection of viral DNA in urine or blood and renal biopsy are the main diagnostic tools. The purpose of this study was to evaluate the use of urine cytology for diagnosis of BKV replication in renal graft recipients. Patients and methods:, We studied 32 de novo renal transplant recipients prospectively with sequential urine samples for a period of 1 year. Thin-Prep methodology was used to prepare the slides. Cytology results were correlated with polymerase chain reaction (PCR) in urine and blood. Results:, Decoy cells indicative of BKV infection were detected in 14 (7.3%) of the 190 urine samples derived from 11 recipients. In three cases with positive decoy cells, BK viraemia and viruria were simultaneously identified. In a further three cases, BKV active replication was confirmed in urine by both cytology and PCR. Conclusions:, Urine cytology is an easy and rapid method of detecting decoy cells in cases where renal biopsy is not possible. However, the low incidence of detection of decoy cells in the present study, together with poor correlation with PCR results, questions its sensitivity and specificity in diagnosing BKV reactivation. [source] Lung transplantation in patients with connective tissue disorders and esophageal dysmotilityDISEASES OF THE ESOPHAGUS, Issue 7 2008Warren J. Gasper SUMMARY., Lung and esophageal dysfunction are common in patients with connective tissue disease (CTD). Recent reports have suggested a link between pathologic gastroesophageal reflux and bronchiolitis obliterans syndrome (BOS) after lung transplant. Because patients with CTD have a high incidence of esophageal dysmotility and reflux, this group may be at increased risk of allograft dysfunction after lung transplantation. Little is known about antireflux surgery in these patients. Our aims were to describe: (i) the esophageal motility and reflux profile of patients with CTD referred for lung transplantation; and (ii) the safety and outcomes of laparoscopic fundoplication in this group. A retrospective review of 26 patients with CTD referred for lung transplantation between July 2003 and June 2007 at a single center. Esophageal studies included manometry and ambulatory 24-h pH monitoring. Twenty-three patients had esophageal manometry and ambulatory 24-h pH monitoring. Nineteen patients (83%) had pathologic distal reflux and 7 (30%) also had pathologic proximal reflux. Eighteen patients (78%) had impaired or absent peristalsis. Eleven of 26 patients underwent lung transplantation. Ten patients are alive at a median follow-up of 26 months (range 3,45) and one has bronchiolitis obliterans syndrome-1. Six patients had a laparoscopic fundoplication, 1 before transplantation and 5 after. All fundoplication patients are alive at median follow-up of 25 months (range 19,45). In conclusion, esophageal dysmotility and reflux are common in CTD patients referred for lung transplant. For this group, laparoscopic fundoplication is safe in experienced hands. [source] A novel prognostic model based on serum levels of total bilirubin and creatinine early after liver transplantationLIVER INTERNATIONAL, Issue 6 2007Xiao Xu Abstract Background/aim: We aim to evaluate the impact of early renal dysfunction (ERD), early allograft dysfunction (EAD) on post-transplant mortality, and further explore a simple and accurate model to predict prognosis. Patients: A total of 161 adult patients who underwent liver transplantation for benign end-stage liver diseases were enrolled in the retrospective study. Another 38 patients were used for model validation. Results: Poor patient survival was associated with ERD or EAD. A post-transplant model for predicting mortality (PMPM) based on serum levels of total bilirubin and creatinine at 24-h post-transplantation was then established according to multivariate logistic regression. At 3 months, 6 months and 1 year, the area under receiver operating characteristic curves (AUC) of PMPM score at 24-h post-transplantation (0.876, 0.878 and 0.849, respectively) were significantly higher than those of pre-transplant model for end-stage liver diseases (MELD) score (0.673, 0.674 and 0.618, respectively) or the post-transplant MELD score at 24-h post-transplantation (0.787, 0.787 and 0.781, respectively) (P<0.05). Patients with PMPM score ,,1.4 (low-risk group, n=114) achieved better survival than those with PMPM score >,1.4 (high-risk group, n=47) (P<0.001). The patients in the high-risk group showed a relatively good outcome if their PMPM scores decreased to ,,1.4 at post-transplant day 7. The subsequent validation study showed that PMPM functioned with a predictive accuracy of 100%. Conclusion: The PMPM score could effectively predict short- and medium-term mortality in liver transplant recipients. [source] Seventh Day Syndrome , acute hepatocyte apoptosis associated with a unique syndrome of graft loss following liver transplantation,LIVER INTERNATIONAL, Issue 1 2001Muhammed Ashraf Memon Abstract:Aim: The aim of this study is to describe a unique 7th day syndrome (7DS), quite different from other causes of post-transplantation allograft dysfunction in a group of orthotopic liver transplant (OLT) patients who needed retransplantation. Methods: A retrospective analysis of 594 consecutive OLT over an 8-year period revealed that 10 patients developed allograft dysfunction approximately 7 days following an initially normal graft function. Results: The features included: (a) severe liver failure; (b) sudden peak of extremely high liver enzymes at approximately day 7; (c) serial liver biopsy findings of central lobular hemorrhage with minimal inflammatory cell infiltrate and (d) an explant with no evidence of vascular thrombosis. The biochemical and morphometric pathological data of these patients were compared with data of patitents who had early acute rejection (AR), hepatic artery thrombosis (HAT), primary non-function (PNF), severe sepsis and no dysfunction. Lastly, serial liver core biopsies and explants were tested for evidence of apoptosis, which revealed a significantly higher number of apoptotic hepatocytes in 7DS compared to all control groups. Conclusions: Seventh Day Syndrome is a distinct entity associated with early graft dysfunction characterized by a marked apoptosis of hepatocytes. Fas receptor activation or other pathways of program cell death may be implicated in occurrence of 7DS. [source] Utility of liver allograft biopsy obtained at procurementLIVER TRANSPLANTATION, Issue 5 2008Irene J. Lo Extended-donor criteria (EDC) liver allografts potentiate the role of procurement biopsy in organ utilization. To expedite allocation, histologic evaluation is routinely performed upon frozen-section (FS) specimens by local pathologists. This descriptive study compares FS reports by local pathologists with permanent-section (PS) evaluation by dedicated hepatopathologists, identifies histologic characteristics underrepresented by FS evaluation, and evaluates the efficacy of a biopsy decision analysis based on organ visualization. Fifty-two liver transplants using EDC allografts evaluated by FS with PS were studied. Pathologic worksheets created by an organ procurement organization were applied in 34 FS. PS analysis included 7 staining procedures for 8 histologic criteria. PS from 56 additional allografts determined not to require donor biopsy were also analyzed. A high correlation was observed between FS and PS. Underestimation of steatosis by FS was associated with allograft dysfunction. Surgical assessment of cholestasis, congestion, and steatosis was accurate whereas inflammation, necrosis, and fibrosis were underestimated in allografts suffering parenchymal injury. In conclusion, the correlation between FS and PS is high, and significant discrepancies are rare. Biopsy is not a prerequisite for EDC utilization but is suggested in hepatitis C, hypernatremia, donation after cardiac death, or multiple EDC indications. Implementation of a universal FS worksheet could standardize histologic reporting and facilitate data collection, allocation, and research. Liver Transpl 2008. © 2008 AASLD. [source] Factors that identify survival after liver retransplantation for allograft failure caused by recurrent hepatitis C infectionLIVER TRANSPLANTATION, Issue 12 2004Guy W. Neff Hepatitis C virus (HCV) is becoming the most common indication for liver retransplantation (ReLTx). This study was a retrospective review of the medical records of liver transplant patients at our institution to determine factors that would identify the best candidates for ReLTx resulting from allograft failure because of HCV recurrence. The patients were divided into 2 groups on the basis of indication for initial liver transplant. Group 1 included ReLTx patients whose initial indication for LTx was HCV. Group 2 included patients who received ReLTx who did not have a history of HCV. We defined chronic allograft dysfunction (AD) as patients with persistent jaundice (> 30 days) beginning 6 months after primary liver transplant in the absence of other reasons. HCV was the primary indication for initial orthotopic liver transplantation (OLT) in 491/1114 patients (44%) from July 1996 to February 2004. The number of patients with AD undergoing ReLTx in Groups 1 and 2 was 22 and 12, respectively. The overall patient and allograft survival at 1 year was 50% and 75% in Groups 1 and 2, respectively (P = .04). The rates of primary nonfunction and technical problems after ReLTx were not different between the groups. However, the incidence of recurrent AD was higher in Group 1 at 32% versus 17% in Group 2 (P = .04). Important factors that predicted a successful ReLTx included physical condition at the time of ReLTx (P = .002) and Child-Turcotte-Pugh score (P = .008). In conclusion, HCV is associated with an increased incidence of chronic graft destruction with a negative effect on long-term results after ReLTx. The optimum candidate for ReLTx is a patient who can maintain normal physical activity. As the allograft shortage continues, the optimal use of cadaveric livers continues to be of primary importance. The use of deceased donor livers in patients with allograft failure caused by HCV remains a highly controversial issue. (Liver Transpl 2004;10:1497,1503.) [source] Autoimmune hepatitis after liver transplantation and other lessons of self-intoleranceLIVER TRANSPLANTATION, Issue 6 2002Albert J. Czaja MD Autoimmune hepatitis has been described as recurrent or de novo disease after transplantation. The legitimacy of these diagnoses and the bases for their occurrence are unknown. To better understand these aspects of allograft dysfunction, the purported pathogenic mechanisms of classical autoimmune hepatitis were reviewed and extrapolated to recurrent and de novo disease after transplantation. Loss of self-tolerance may relate to defects in the negative selection of autoreactive immunocytes and the clonal expansion of promiscuous lymphocytes that are cross-reactive to homologous antigens (molecular mimicry). Repopulation of the allograft with recipient antigen-presenting cells and the presence of primed promiscuous cytotoxic T cells within the recipient are likely factors for recurrent disease. Targets may be the same peptides that triggered the original disease, donor-derived class II antigens of the major histocompatibility complex, or homologous antigens associated with unidentified hepatotrophic viruses. De novo disease is probably due to similar mechanisms, but its predilection for children suggests that thymic dysfunction associated with cyclosporine treatment may be a factor. Corticosteroid therapy is effective in each condition. In conclusion, recurrent and de novo autoimmune hepatitis after transplantation are examples of self-intolerance. The mechanisms that perturb immunologic homeostasis in this human model of the classical disease must be studied more rigorously. [source] Late hepatic allograft dysfunctionLIVER TRANSPLANTATION, Issue 11B 2001Professor of Medicine Russell H. Wiesner MD Key Points 1Lifelong monitoring of graft function, immunosuppressive levels, and screening for drug toxicity is required in all liver recipients. 2Late hepatic allograft dysfunction is common and is caused by a variety of etiologies including rejection, infection, biliary/vascular abnormalities, recurrence of disease, and drug hepatotoxicity. 3In all patients with late hepatic allograft dysfunction, liver biopsy should be performed to assess for the presence of rejection, and to thus avoid excessive use of bolus corticosteroid therapy and guide appropriate immunosuppressive management. 4Recurrence of disease is the most common cause of late hepatic allograft dysfunction. 5Hepatitis C universally reinfects the hepatic allograft, and is associated with decreased patient and graft survival and leads to the recurrence of cirrhosis in 28% of patients within 5 years of transplantation. 6Major advances have been made in preventing recurrence of hepatitis B by the use of hepatitis B immune globulin in combination with lamivudine therapy. 7Autoimmune liver diseases such as primary biliary cirrhosis, primary sclerosing cholangitis, and autoimmune hepatitis have a recurrence rate of approximately 20% to 30%. 8In patients developing recurrence of autoimmune hepatitis, steroid withdrawal is the most common cause. 9Recurrent hepatocellular cancer can be markedly reduced if strict guidelines are adhered to in selecting patients. 10Drug hepatotoxicity must always be considered in the differential diagnosis of late hepatic allograft dysfunction. [source] BK viral infection in an Australian pediatric renal transplant populationPEDIATRIC TRANSPLANTATION, Issue 5 2004L. Haysom Abstract: BK virus (BKV) is recognized as a significant cause of renal allograft dysfunction in adults, and there is growing awareness of its importance in the pediatric population. Eighteen pediatric renal transplant recipients and 18 age-matched controls were prospectively studied. Anti-BKV immunoglobulin G (IgG) and IgM titres were assayed in all subjects at entry to the study. Polymerase chain reaction (PCR) for BKV DNA was performed on urine and serum at entry, and prospectively tested again at 4, 8 and 12 months. Mean age ± s.d. of transplant recipients and controls was 14.6 ± 3.3 and 13.9 ± 0.33 yr respectively [not significant (NS)]. Transplant patients were studied at a mean time of 5.6 ± 4.2 yr post-transplant. 56% of transplant patients and 39% of controls were seropositive (+ve BKV IgG) (NS). Plasma BKV PCR was positive in one transplant patient (who also had positive urine PCR) and in none of the controls. The prevalence of positive urine PCR in transplant patients was greater than in controls (33% vs. 0%, p = 0.02). Positive urine BKV PCR was more commonly found in patients treated with mycophenolate than azathioprine (p = 0.04). We conclude that the prevalence of BKV seropositivity and viral activation in this Australian pediatric renal transplant population is similar to that reported in adult and pediatric populations in other countries. BK viruria was more common in children with greater immunosuppression, suggesting that this group is at higher risk of BKV induced nephropathy. [source] Allograft diabetic nephropathy may progress to end-stage renal diseasePEDIATRIC TRANSPLANTATION, Issue 4 2004Moro O. Salifu Abstract:, Mesangial expansion and glomerular basement membrane thickening characteristic of diabetic nephropathy recur in diabetic recipients of renal allografts from non-diabetic donors but progression to renal failure is minimally documented. Three female renal allograft recipients (aged 40, 62 and 73 yr), who developed end-stage renal disease (ESRD) due to recurrent diabetic nephropathy (two patients) and de novo diabetes (one patient) are reported. Onset of proteinuria, uncontrolled hypertension, azotemia, renal allograft pathologic findings and the need for hemodialysis were analyzed. None of the kidney donors (one cadaver, two living related) had known diabetes or perturbed glucose metabolism pre-transplantation. The three patients presented had different varieties of diabetes; type 1, type 2 and new onset diabetes after transplantation (NODAT). In each subject, proteinuria was detected by dipstick at a mean of 8.3 yr (range 8,9) post-transplantation and increased to the nephrotic range (3.7,4.8 g/day) inducing hypoalbuminemia and azotemia. A histopathologic diagnosis of allograft diabetic nephropathy was made in a mean of 11.7 yr (range 10,14), based on glomerular basement membrane thickening, nodular and diffuse intercapillary glomerulosclerosis, arteriolosclerosis, and tubular atrophy with marked tubular basement membrane thickening characteristic of advanced diabetic nephropathy. All three patients manifested uremia and resumed hemodialysis. Two patients died from sepsis within 2 months and one patient died 2.5 yr later after resumption of maintenance hemodialysis. We infer that recurrent or de novo diabetic nephropathy in renal allografts follows a clinical decade-long course irrespective of diabetes. Reports of ESRD due to allograft diabetic nephropathy (ADN) have been limited because of shorter survival of diabetic transplant recipients and few kidney biopsies performed in patients with chronic allograft dysfunction. The occurrence of allograft diabetic nephropathy in some, but not all patients, however, suggests that individual genetic variability modulates disease expression. [source] Histopathologic Clusters Differentiate Subgroups Within the Nonspecific Diagnoses of CAN or CR: Preliminary Data from the DeKAF StudyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010A. J. Matas The nonspecific diagnoses ,chronic rejection',CAN', or ,IF/TA' suggest neither identifiable pathophysiologic mechanisms nor possible treatments. As a first step to developing a more useful taxonomy for causes of new-onset late kidney allograft dysfunction, we used cluster analysis of individual Banff score components to define subgroups. In this multicenter study, eligibility included being transplanted prior to October 1, 2005, having a ,baseline' serum creatinine ,2.0 mg/dL before January 1, 2006, and subsequently developing deterioration of graft function leading to a biopsy. Mean time from transplant to biopsy was 7.5 ± 6.1 years. Of the 265 biopsies (all with blinded central pathology interpretation), 240 grouped into six large (n > 13) clusters. There were no major differences between clusters in recipient demographics. The actuarial postbiopsy graft survival varied by cluster (p = 0.002). CAN and CNI toxicity were common diagnoses in each cluster (and did not differentiate clusters). Similarly, C4d and presence of donor specific antibody were frequently observed across clusters. We conclude that for recipients with new-onset late graft dysfunction, cluster analysis of Banff scores distinguishes meaningful subgroups with differing outcomes. [source] Recurrence-Free Long-Term Survival After Liver Transplantation in Patients with 18F-FDG Non-Avid Hilar Cholangiocarcinoma on PETAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009A. Kornberg The aim of this retrospective study was to assess the value of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) for predicting biological tumor behavior and outcome after liver transplantation (LT) in patients with otherwise unresectable hilar cholangiocarcinoma (HC). Preoperative 18F-FDG-PET scanning was performed in 13 patients with type IV Klatskin tumor before LT. PET+ status indicated patients with an increased pretransplant 18F-FDG uptake, whereas PET, recipients had no increased preoperative 18F-FDG uptake on PET. Pretransplant PET findings were correlated with histopathological tumor characteristics and patient outcome after LT. Eight patients demonstrated positive preoperative PET findings (61.5%), whereas five patients had no increased preoperative 18F-FDG tumor uptake (38.5%) on PET. One PET+ patient died after 1 month due to liver allograft dysfunction. Seven PET+ liver recipients developed tumor recurrence, whereas five PET, patients were tumor-free alive after a median of 76 months post-LT (p = 0.001). The 2-year recurrence-free survival rate after LT was 100% in PET, patients and 28.6% in the PET+ population (log-rank = 0.008). Our results suggest that patients with 18F-FDG non-avid HC on PET may achieve recurrence-free long-term survival after LT. [source] Long-term Management of the Liver Transplant Patient: Recommendations for the Primary Care DoctorAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009B. M. McGuire No official document has been published for primary care physicians regarding the management of liver transplant patients. With no official source of reference, primary care physicians often question their care of these patients. The following guidelines have been approved by the American Society of Transplantation and represent the position of the association. The data presented are based on formal review and analysis of published literature in the field and the clinical experience of the authors. These guidelines address drug interactions and side effects of immunosuppressive agents, allograft dysfunction, renal dysfunction, metabolic disorders, preventive medicine, malignancies, disability and productivity in the workforce, issues specific to pregnancy and sexual function, and pediatric patient concerns. These guidelines are intended to provide a bridge between transplant centers and primary care physicians in the long-term management of the liver transplant patient. [source] Correlation of Donor-Specific Antibodies, Complement and Its Regulators with Graft Dysfunction in Cardiac Antibody-Mediated RejectionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 9 2009C. D. Tan Antibody-mediated rejection (AMR) is an immunopathologic process in which activation of complement often results in allograft injury. This study correlates C4d and C3d with HLA serology and graft function as diagnostic criteria for AMR. Immunofluorescence staining for C4d and C3d was performed on 1511 biopsies from 330 patients as part of routine diagnostic work-up of rejection. Donor-specific antibodies were detected in 95% of those with C4d+C3d+ biopsies versus 35% in the C4d+C3d, group (p = 0.002). Allograft dysfunction was present in 84% in the C4d+ C3d+ group versus 5% in the C4d+C3d, group (p < 0.0001). Combined C4d and C3d positivity had a sensitivity of 100% and specificity of 99% for the pathologic diagnosis of AMR and a mortality of 37%. Since activation of complement does not always result in allograft dysfunction, we correlated the expression pattern of the complement regulators CD55 and CD59 in patients with and without complement deposition. The proportion of patients with CD55 and/or CD59 staining was highest in C4d+C3d, patients without allograft dysfunction (p = 0.03). We conclude that a panel of C4d and C3d is diagnostically more useful than C4d alone in the evaluation of AMR. CD55 and CD59 may play a protective role in patients with evidence of complement activation. [source] Fate of the Mate: The Influence of Delayed Graft Function in Renal Transplantation on the Mate RecipientAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009J. F. Johnson Delayed graft function (DGF) in a deceased-donor renal recipient is associated with allograft dysfunction 1-year posttransplant. There is limited research about the influence to allograft function on the mate of a DGF recipient over time. Using a retrospective cohort design, we studied 55 recipients from a single center. The primary outcome was the change in glomerular filtration rate (GFR) 1-year posttransplant. The secondary outcome was the GFR at baseline. We found that mates to DGF recipients had a mean change in GFR 1-year posttransplant of ,11.2 mL/min, while the control group had a mean change of ,0.4 mL/min. The difference in the primary outcome was significant (p = 0.025) in a multivariate analysis, adjusting for cold ischemic time, panel reactive antibody level, allograft loss, human leukocyte antibody (HLA)-B mismatches and HLA-DR mismatches. No significant difference between groups was found in baseline GFR. In conclusion, mates to DGF recipients had a significantly larger decline in allograft function 1-year posttransplant compared to controls with similar renal function at baseline. We believe strategies that may preserve allograft function in these,at-risk'recipients should be developed and tested. [source] Targeting Allograft Injury and Inflammation in the Management of Post-Lung Transplant Bronchiolitis Obliterans SyndromeAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009A. G. N. Robertson Chronic allograft dysfunction, manifesting as bronchiolitis obliterans syndrome (BOS), is the major cause of morbidity and mortality in human lung transplant recipients. While alloimmunity has a definite role, there is increasing interest in overall allograft injury and subsequent inflammation and remodeling. This review deals with nonalloimmune factors that may potentiate alloimmune injury. We discuss infection and reflux/aspiration as examples of allograft injury, which may lead to chronic loss of graft function and BOS. Surgical and nonsurgical treatments aimed at preventing these insults and improving survival are considered. The need for further evidence, including randomized-controlled trials, to evaluate the role of medical and surgical therapies is emphasized by the current literature. [source] Follicular Bronchiolitis: A Rare Cause of Bronchiolitis Obliterans Syndrome After Lung Transplantation: A Case ReportAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009R. Vos This case report is the first confirmed case of follicular bronchiolitis (FB), a rare bronchiolar disorder characterized by peribronchiolar lymphoid follicles, in a series of over 400 lung transplantations performed in our center. It is to our knowledge, the first publication describing FB after lung transplantation (LTx), presenting as chronic allograft dysfunction or bronchiolitis obliterans syndrome (BOS). [source] Acute Oxalate Nephropathy Causing Late Renal Transplant Dysfunction Due to Enteric HyperoxaluriaAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2008A. C. Rankin Calcium oxalate (CaOx) deposition in the renal allograft is an under recognized and important cause of acute tubular injury and early allograft dysfunction. We present a case of late transplant dysfunction due to acute oxalate nephropathy. The patient presented with diarrhea and deteriorating graft function, and a diagnosis of enteric hyperoxaluria secondary to pancreatic insufficiency was made. This had occurred, as the patient had been noncompliant with his pancreatic enzyme replacement therapy. Treatment to reduce his circulating oxalate load was initiated, including twice-daily hemodialysis, low fat and oxalate diet and appropriate administration of pancreatic enzyme supplements. Graft function subsequently recovered. The possibility of fat malabsorption leading to enteric hyperoxaluria should be considered in renal graft recipients presenting with loose stools and graft dysfunction. [source] Airway Epithelial Cell Senescence in the Lung AllograftAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2008S. M. Parker Chronic lung allograft dysfunction, manifesting as bronchiolitis obliterans syndrome (BOS), is characterized by airway epithelial injury, impaired epithelial regeneration and subsequent airway remodeling. Increased cellular senescence has been reported in renal and liver allografts affected by chronic allograft dysfunction but the significance of cellular senescence in the airway epithelium of the transplanted lung is unknown. Thirty-four lung transplant recipients, 20 with stable graft function and 14 with BOS, underwent transbronchial lung biopsy and histochemical studies for senescence markers in small airways. Compared to nontransplant control lung tissue (n = 9), lung allografts demonstrate significantly increased airway epithelial staining for senescence-associated beta galactosidase (SA ,-gal) (p = 0.0215), p16ink4a (p = 0.0002) and p21waf1/cip (p = 0.0138) but there was no difference in expression of these markers between stable and BOS affected recipients (p > 0.05). This preliminary cross-sectional study demonstrates that cellular senescence occurs with increased frequency in the airway epithelium of the lung allograft but does not establish any association between airway epithelial senescence and BOS. A prospective longitudinal study is required to better address any potential causal association between airway epithelial senescence in stable allograft recipients and the subsequent development of BOS. [source] Banff Schema for Grading Pancreas Allograft Rejection: Working Proposal by a Multi-Disciplinary International Consensus PanelAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2008C. B. Drachenberg Accurate diagnosis and grading of rejection and other pathological processes are of paramount importance to guide therapeutic interventions in patients with pancreas allograft dysfunction. A multi-disciplinary panel of pathologists, surgeons and nephrologists was convened for the purpose of developing a consensus document delineating the histopathological features for diagnosis and grading of rejection in pancreas transplant biopsies. Based on the available published data and the collective experience, criteria for the diagnosis of acute cell-mediated allograft rejection (ACMR) were established. Three severity grades (I/mild, II/moderate and III/severe) were defined based on lesions known to be more or less responsive to treatment and associated with better- or worse-graft outcomes, respectively. The features of chronic rejection/graft sclerosis were reassessed, and three histological stages were established. Tentative criteria for the diagnosis of antibody-mediated rejection were also characterized, in anticipation of future studies that ought to provide more information on this process. Criteria for needle core biopsy adequacy and guidelines for pathology reporting were also defined. The availability of a simple, reproducible, clinically relevant and internationally accepted schema for grading rejection should improve the level of diagnostic accuracy and facilitate communication between all parties involved in the care of pancreas transplant recipients. [source] Postrenal Transplant Hemophagocytic Lymphohistiocytosis and Thrombotic Microangiopathy Associated with Parvovirus B19 InfectionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2008M. R. Ardalan Persistent anemia is a known consequence of Parvovirus B19 (B19) infection following renal transplantation. However, to date, no description of B19-related hemophagocytic lymphohistiocytosis (HLH) exists in renal transplant recipients. We report a 24-year-old male kidney recipient, who presented with fever, severe anemia and allograft dysfunction two years following transplantation. Hyperferritinemia, hypertriglyceridemia, elevated serum lactate dehydrogenase, pancytopenia and fragmented red blood cells on the peripheral blood were also noted. Bone marrow examination revealed giant pronormoblasts and frequent histiocytes with intracellular hematopoietic elements, consistent with HLH. Renal allograft biopsy revealed closure of the lumen of glomerular capillaries and thickening of the capillary walls compatible with thrombotic microangiopathy. The presence of anti-B19 IgM antibody and viral DNA in the patient's serum (detected by real-time PCR) confirmed an acute B19 infection. Following high-dose intravenous immunoglobulin therapy, the anemia gradually resolved and renal function improved. As far as we know, this is the first report of B19-associated HLH and thrombotic microangiopathy in a renal transplant recipient. [source] Monocyte Infiltration and Kidney Allograft Dysfunction During Acute RejectionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2008R. Girlanda Multiple cell types infiltrate acutely rejecting renal allografts. Typically, monocytes and T cells predominate. Although T cells are known to be required for acute rejection, the degree to which monocytes influence this process remains incompletely defined. Specifically, it has not been established to what degree monocytes impact the clinical phenotype of rejection or how their influence compares to that of T cells. We therefore investigated the relative impact of T cells and monocytes by correlating their presence as measured by immunohistochemical staining with the magnitude of the acute change in renal function at the time of biopsy in 78 consecutive patients with histological acute rejection. We found that functional impairment was strongly associated with the degree of overall cellular infiltration as scored using Banff criteria. However, when cell types were considered, monocyte infiltration was quantitatively associated with renal dysfunction while T-cell infiltration was not. Similarly, renal tubular stress, as indicated by HLA-DR expression, increased with monocyte but not T-cell infiltration. These data suggest that acute allograft dysfunction is most closely related to monocyte infiltration and that isolated T-cell infiltration has less acute functional impact. This relationship may be useful in assigning acute clinical relevance to biopsy findings. [source] Impact of Cyclosporine Reduction With MMF: A Randomized Trial in Chronic Allograft Dysfunction.AMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2006Reference' Study Long-term use of calcineurine inhibitors (CNIs) may contribute to the development of chronic allograft dysfunction (CAD). We investigate the impact of the introduction of MMF combined with cyclosporine (CsA) 50% dose reduction. An open, randomized, controlled, multicenter, prospective study was conducted in 103 patients, receiving a CsA-based therapy with a serum creatinine between 1.7,3.4 mg/dL, more than 1 year after transplantation. They were randomized to receive MMF with half dose of CsA (MMF group) or to continue their maintenance CsA dose (control group). A total of 96 weeks after randomization, the evolution of renal function assessed by regression line analysis of 1/SeCr improved in the MMF group (positive slope) vs. the control group (negative slope), 4.2 × 10,4 vs. ,3.0 × 10,4, respectively (p < 0.001). Concurrently, the absolute renal function improved significantly in the MMF group. No episode of biopsy-proven acute rejection occurred. One patient in each group lost his graft because of biopsy-proven chronic allograft nephropathy. There was a significant decrease of triglycerides level in the MMF group. Anemia and diarrhea were statistically more frequent in the MMF group. In CAD, the reduction of CsA in the presence of MMF results in significant improvement in renal function during a 2-year follow-up. [source] Obesity is Associated with Worsening Cardiovascular Risk Factor Profiles and Proteinuria Progression in Renal Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2005Kirsten A. Armstrong Obesity is associated with adverse cardiovascular (CV) parameters and may be involved in the pathogenesis of allograft dysfunction in renal transplant recipients (RTR). We sought the spectrum of body mass index (BMI) and the relationships between BMI, CV parameters and allograft function in prevalent RTR. Data were collected at baseline and 2 years on 90 RTR (mean age 51 years, 53% male, median transplant duration 7 years), categorized by BMI (normal, BMI , 24.9 kg/m2; pre-obese, BMI 25,29.9 kg/m2; obese, BMI , 30 kg/m2). Proteinuria and glomerular filtration rate (eGFRMDRD) were determined. Nine percent RTR were obese pre-transplantation compared to 30% at baseline (p < 0.001) and follow-up (25 ± 2 months). As BMI increased, prevalence of metabolic syndrome and central obesity increased (12 vs 48 vs 85%, p < 0.001 and 3 vs 42 vs 96%, p < 0.001, respectively). Systolic blood pressure, fasting blood glucose and lipid parameters changed significantly with BMI category and over time. Proteinuria progression occurred in 65% obese RTR (23 (13,59 g/mol creatinine) to 59 (25,120 g/mol creatinine)). BMI was independently associated with proteinuria progression (ß 0.01, p = 0.008) but not with changing eGFRMDRD. In conclusion, obesity is common in RTR and is associated with worsening CV parameters and proteinuria progression. [source] Prednisone-Free Maintenance Immunosuppression,A 5-Year ExperienceAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2005Arthur J. Matas Concern persists that prednisone-free maintenance immunosuppression in kidney transplant recipients will be associated with an increase in late allograft dysfunction and graft loss. We herein report 5-year follow-up of a trial of prednisone-free maintenance immunosuppression. From October 1, 1999, through January 31, 2005, at our center, 589 kidney transplant recipients were treated with a protocol incorporating discontinuation of their prednisone on postoperative day 6. At 5 years, actuarial patient survival was 91%; graft survival, 84%; death-censored graft survival, 92%; acute rejection-free graft survival, 84% and chronic rejection-free graft survival, 87%. The mean serum creatinine level (±SD) at 1 year was 1.6 ± 0.6; at 5 years, 1.7 ± 0.8. In all, 86% of kidney recipients with functioning grafts remain prednisone-free as of April 30, 2005. As compared with historical controls, recipients on prednisone-free maintenance immunosuppression had a significantly lower rate of a number of complications, including cataracts (p < 0.001), posttransplant diabetes mellitus (p < 0.001), avascular necrosis (p = 0.001), and fractures (p = 0.004). We conclude that prednisone-related side effects can be minimized in a protocol incorporating prednisone-free maintenance immunosuppression. Five-year graft outcome remains good. [source] Minimal Acute Rejection after Lung Transplantation: A Risk for Bronchiolitis Obliterans SyndromeAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2005Anthony P. Khalifah Bronchiolitis obliterans syndrome (BOS) is a major cause of lung allograft dysfunction. Although previous studies have identified mild to severe rejection (grade ,A2) as a risk factor for BOS, the role of minimal rejection (grade A1) remains unclear. To determine if A1 rejection by itself is a risk factor for BOS, we performed a retrospective cohort study on 228 adult lung transplant recipients over a 7-year period. Cohorts were defined by their most severe rejection episode (none, A1 only, and ,A2) and analyzed for the subsequent development and progression of BOS using univariate and multivariate time-dependent Cox regression analysis. In the univariate model, the occurrence of isolated minimal rejection was a risk factor for all stages of BOS. Similarly, multivariate models that included HLA mismatch, cytomegalovirus pneumonitis, community acquired viral infection, underlying disease and type of transplant demonstrated that A1 rejection was a distinct risk factor for BOS. Furthermore, the associated risk with A1 rejection was slightly greater than the risk from ,A2 and treatment of A1 rejection decreased the risk for subsequent BOS stage 1. We conclude that minimal rejection is associated with an increased risk for BOS development and progression that is comparable to A2 rejection. [source] | ||||||||||