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Allograft Loss (allograft + loss)
Selected AbstractsRENAL ALLOGRAFT LOSS , THE AUSTRALIAN EXPERIENCE, 1988-1997NEPHROLOGY, Issue 3 2000Esther Briganti [source] Reducing De Novo Donor-Specific Antibody Levels during Acute Rejection Diminishes Renal Allograft LossAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009M. J. Everly The effect of de novo DSA detected at the time of acute cellular rejection (ACR) and the response of DSA levels to rejection therapy on renal allograft survival were analyzed. Kidney transplant patients with acute rejection underwent DSA testing at rejection diagnosis with DSA levels quantified using Luminex single-antigen beads. Fifty-two patients experienced acute rejection with 16 (31%) testing positive for de novo DSA. Median follow-up was 27.0 ± 17.4 months postacute rejection. Univariate analysis of factors influencing allograft survival demonstrated significance for African American race, DGF, cytotoxic PRA >20% (current) and/or >50% (peak), de novo DSA, C4d and repeat transplantation. Multivariate analysis showed only de novo DSA (6.6-fold increased allograft loss risk, p = 0.017) to be significant. Four-year allograft survival was higher with ACR (without DSA) (100%) than mixed acute rejection (ACR with DSA/C4d) (65%) or antibody-mediated rejection (35%) (p < 0.001). Patients with >50% reduction in DSA within 14 days experienced higher allograft survival (p = 0.039). De novo DSAs detected at rejection are associated with reduced allograft survival, but prompt DSA reduction was associated with improved allograft survival. DSA should be considered a potential new end point for rejection therapy. [source] Identifying Specific Causes of Kidney Allograft LossAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009Z. M. El-Zoghby The causes of kidney allograft loss remain unclear. Herein we investigated these causes in 1317 conventional kidney recipients. The cause of graft loss was determined by reviewing clinical and histologic information the latter available in 98% of cases. During 50.3 ± 32.6 months of follow-up, 330 grafts were lost (25.0%), 138 (10.4%) due to death with function, 39 (2.9%) due to primary nonfunction and 153 (11.6%) due to graft failure censored for death. The latter group was subdivided by cause into: glomerular diseases (n = 56, 36.6%); fibrosis/atrophy (n = 47, 30.7%); medical/surgical conditions (n = 25, 16.3%); acute rejection (n = 18, 11.8%); and unclassifiable (n = 7, 4.6%). Glomerular pathologies leading to failure included recurrent disease (n = 23), transplant glomerulopathy (n = 23) and presumed nonrecurrent disease (n = 10). In cases with fibrosis/atrophy a specific cause(s) was identified in 81% and it was rarely attributable to calcineurin inhibitor (CNI) toxicity alone (n = 1, 0.7%). Contrary to current concepts, most cases of kidney graft loss have an identifiable cause that is not idiopathic fibrosis/atrophy or CNI toxicity. Glomerular pathologies cause the largest proportion of graft loss and alloinmunity remains the most common mechanism leading to failure. This study identifies targets for investigation and intervention that may result in improved kidney transplantation outcomes. [source] NOS2 (iNOS) Deficiency in Kidney Donor Accelerates Allograft Loss in a Murine ModelAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2007C. Du Renal NOS2 is expressed and produces abundant nitric oxide (NO) in various renal cells in response to proinflammatory cytokines. However, the role of this enzyme in renal allograft survival remains unknown. Kidney allotransplantation was performed in the murine model of C57BL/6J (H-2d) to nephrectomized Balb/c (H-2b) mice. Here we show that deficiency in NOS2 expression in kidney donors significantly advanced allograft failure, indicated by decreasing mean survival of recipients receiving NOS2 null grafts (15.4 ± 6.4 days) as compared to those with wild type grafts (65.4 ± 28.1 days) (p = 0.0005). Consistent with survival results, NOS2 null grafts had more severe renal tubule injury and decreased renal function compared to wild type grafts. In vitro NOS2 expressing TEC had greater resistance to allogeneic lymphocyte-mediated apoptosis. The addition of exogenous NO inhibited Fas-mediated TEC apoptosis and reduced proliferation of allogeneic lymphocytes. These data suggest that endogenous production of NO through renal NOS2 activity can play a protective role in kidney grafts through attenuating Fas-mediated donor cell apoptosis as well as by inhibiting proliferation of inflammatory infiltrating lymphocytes. Enhanced donor NOS2 expression may be a useful strategy to improve kidney transplant survival. [source] Risk factors and impact of recurrent lupus nephritis in patients with systemic lupus erythematosus undergoing renal transplantation: Data from a single US institutionARTHRITIS & RHEUMATISM, Issue 9 2009Paula I. Burgos Objective To determine the risk factors for recurrent lupus nephritis, allograft loss, and survival among patients with systemic lupus erythematosus (SLE) undergoing kidney transplantation. Methods The archival records of all kidney transplant recipients with a prior diagnosis of SLE (according to the American College of Rheumatology criteria) from June 1977 to June 2007 were reviewed. Patients who had died or lost the allograft within 90 days of engraftment were excluded. Time-to-event data were examined by univariable and multivariable Cox proportional hazards regression analyses. Results Two hundred twenty of nearly 7,000 renal transplantations were performed in 202 SLE patients during the 30-year interval. Of the 177 patients who met the criteria for study entry, the majority were women (80%) and African American (65%), the mean age was 35.6 years, and the mean disease duration was 11.2 years. Recurrent lupus nephritis was noted in 20 patients (11%), allograft loss in 69 patients (39%), and death in 36 patients (20%). African American ethnicity was found to be associated with a shorter time-to-event for recurrent lupus nephritis (hazard ratio [HR] 4.63, 95% confidence interval [95% CI] 1.29,16.65) and death (HR 2.47, 95% CI 0.91,6.71), although, with the latter, the association was not statistically significant. Recurrent lupus nephritis and chronic rejection of the kidney transplant were found to be risk factors for allograft loss (HR 2.48, 95% CI 1.09,5.60 and HR 2.72, 95% CI 1.55,4.78, respectively). In patients with recurrent lupus nephritis, the lesion in the engrafted kidney was predominantly mesangial, compared with a predominance of proliferative or membranous lesions in the native kidneys. Conclusion African American ethnicity was independently associated with recurrent lupus nephritis. Allograft loss was associated with chronic transplant rejection and recurrence of lupus nephritis. Recurrent lupus nephritis is infrequent and relatively benign, without influence on a patient's survival. [source] A retrospective review of the outcome of plasma exchange and aggressive medical therapy in antibody mediated rejection of renal allografts: A single center experienceJOURNAL OF CLINICAL APHERESIS, Issue 6 2008Wisam Al-Badr Abstract Antibody-mediated rejection (AMR) has been recognized as a major cause of renal allograft loss. Protocols using plasma exchange (PE) to reverse rejection have mixed results. Methods: A retrospective chart review was performed to determine the clinical response to PE inpatients with AMR of renal allograft. A good response to treatment was defined as a decline in serum creatinine (SCr) to within 25% above the prerejection value or discontinuation of dialysis with a SCr <2 mg/dl within 3 months of discharge from the hospital and disappearance of donor-specific alloantibodies (DSA). Results: Twenty-two patients, treated with PE for biopsy proven AMR with or without acute-cellular rejection (ACR), were included in the study. Sixty-four percent of patients had concurrent AMR and ACR. Fifty-two percent of all patients had a good response to antirejection therapy, whereas 63% of patients with only AMR and 46% of patients with both AMR and ACR had a good response. Good response to PE did not correlate with the number of plasma volumes exchanged (P = 0.09), but correlated with a shorter period from transplantation to the rejection episode (P = 0.002). Conclusion: Only a shorter interval between transplantation and the acute rejection episode correlated with a good response to PE. J. Clin. Apheresis, 2008. © 2008 Wiley-Liss, Inc. [source] Native BK viral nephropathy in a pediatric heart transplant recipientPEDIATRIC TRANSPLANTATION, Issue 4 2010Farah N. Ali Ali FN, Meehan SM, Pahl E, Cohn RA. Native BK viral nephropathy in a pediatric heart transplant recipient. Pediatr Transplantation 2010: 14:E38,E41. © 2009 Wiley Periodicals, Inc. Abstract:, BK viral nephropathy is a well-documented clinical entity in kidney transplant recipients and a significant cause of morbidity and allograft loss in affected patients. BK viral nephropathy in native kidneys of non-kidney transplant recipients is relatively uncommon, but has been reported in adult patients. We report the occurrence of BK viral nephropathy in a pediatric heart transplant recipient. A 10-yr-old boy with past history of Ewing's sarcoma underwent heart transplantation for dilated cardiomyopathy induced by previous chemotherapy with doxorubicin. Post-transplant course was complicated by grade 3A rejection and CMV colitis. He was diagnosed with native BK viral nephropathy approximately 18 months post-transplant due to mild, but persistent, elevation in serum creatinine associated with proteinuria. BK viral nephropathy affects non-kidney transplant recipients, and a high index of suspicion is necessary for early diagnosis and management of this condition. [source] Efficacy of Induction Therapy with ATG and Intravenous Immunoglobulins in Patients with Low-Level Donor-Specific HLA-AntibodiesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2010K. Bächler Low-level donor-specific HLA-antibodies (HLA-DSA) (i.e. detectable by single-antigen flow beads, but negative by complement-dependent cytotoxicity crossmatch) represent a risk factor for early allograft rejection. The short-term efficacy of an induction regimen consisting of polyclonal anti-T-lymphocyte globulin (ATG) and intravenous immunoglobulins (IvIg) in patients with low-level HLA-DSA is unknown. In this study, we compared 67 patients with low-level HLA-DSA not having received ATG/IvIg induction (historic control) with 37 patients, who received ATG/IvIg induction. The two groups were equal regarding retransplants, HLA-matches, number and class of HLA-DSA. The overall incidence of clinical/subclinical antibody-mediated rejection (AMR) was lower in the ATG/IvIg than in the historic control group (38% vs. 55%; p = 0.03). This was driven by a significantly lower rate of clinical AMR (11% vs. 46%; p = 0.0002). Clinical T-cell-mediated rejection (TCR) was significantly lower in the ATG/IvIg than in the historic control group (0% vs. 50%; p < 0.0001). Within the first year, allograft loss due to AMR occurred in 7.5% in the historic control and in 0% in the ATG/IvIg group. We conclude that in patients with low-level HLA-DSA, ATG/IvIg induction significantly reduces TCR and the severity of AMR, but the high rate of subclinical AMR suggests an insufficient control of the humoral immune response. [source] Baseline Donor-Specific Antibody Levels and Outcomes in Positive Crossmatch Kidney TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2010J. M. Gloor Renal transplant candidates with donor-specific alloantibody (DSA) have increased risk of antibody-mediated allograft injury. The goal of this study was to correlate the risk of antibody-mediated rejection (AMR), transplant glomerulopathy (TG) and graft survival with the baseline DSA level (prior to initiation of pretransplant conditioning). These analyses include 119 positive crossmatch (+XM) compared to 70 negative crossmatch (,XM) transplants performed between April 2000 and July 2007. Using a combination of cell-based crossmatch tests, DSA level was stratified into very high +XM, high +XM, low +XM and ,XM groups. In +XM transplants, increasing DSA level was associated with increased risk for AMR (HR = 1.76 [1.51, 2.07], p = 0.0001) but not TG (p = 0.18). We found an increased risk for both early and late allograft loss associated with very high DSA (HR = 7.71 [2.95, 20.1], p = 0.0001). Although lower DSA recipients commonly developed AMR and TG, allograft survival was similar to that of ,XM patients (p = 0.31). We conclude that the baseline DSA level correlates with risk of early and late alloantibody-mediated allograft injury. With current protocols, very high baseline DSA patients have high rates of AMR and poor long-term allograft survival highlighting the need for improved therapy for these candidates. [source] A Randomized Double-Blind, Placebo Controlled Trial of Steroid Withdrawal after Pediatric Renal TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010M. R. Benfield In an effort to reduce rejection, extend allograft survival and minimize complications, we hypothesized that robust immunosuppression during the first 6 months after transplantation would allow for the safe withdrawal of steroids. A total of 274 pediatric subjects were enrolled and received an anti-CD25 antibody, sirolimus, calcineurin inhibitor and steroids. At 6 months after transplantation, subjects were randomized to steroid withdrawal (n = 73) versus continued low-dose steroids (n = 59). This study was stopped prior to target enrollment because of the incidence of post-transplant lymphoproliferative disorder. At the time of study termination, 132 subjects had been randomized and were available for analysis. At 18 months after transplantation, there was no difference in the standardized height z score; however, the standardized height velocity was greater in the steroid withdrawal group compared to the control group (p = 0.033). There were no differences in acute rejection episodes between treatment groups. The 3-year allograft survival rate was 84.5% in the control group and 98.6% in the steroid withdrawal group (p = 0.002). The immunosuppressive protocol utilized in this study allowed for the withdrawal of steroids without an increased risk of rejection or allograft loss. However, the complications associated with the use of this immunosuppressive protocol were too high to recommend its routine use in pediatric patients. [source] Transplant Outcomes and Economic Costs Associated with Patient Noncompliance to ImmunosuppressionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009B. W. Pinsky We describe factors associated with immunosuppression compliance after kidney transplantation and examine relationships between compliance with allograft outcomes and costs. Medicare claims for immunosuppression in 15 525 renal transplant recipients with at least 1 year of graft function were used to calculate compliance as medication possession ratio. Compliance was categorized by quartiles as poor, fair, good and excellent. We modeled adjusted associations of clinical factors with the likelihood of persistent compliance by multiple logistic regressions (aOR), and estimated associations of compliance with subsequent graft and patient survival with Cox proportional hazards (aHR). Adolescent recipients aged 19,24 years were more likely to be persistently noncompliant compared to patients aged 24,44 years (aOR 1.49 [1.06,2.10]). Poor (aHR 1.80 [1.52,2.13]) and fair (aHR 1.63[1.37,1.93]) compliant recipients were associated with increased risks of allograft loss compared to the excellent compliant recipients. Persistent low compliance was associated with a $12 840 increase in individual 3-year medical costs. Immunosuppression medication possession ratios indicative of less than the highest quartile of compliance predicted increased risk of graft loss and elevated costs. These findings suggest that interventions to improve medication compliance among kidney transplant recipients should emphasize the benefits of maximal compliance, rather than discourage low compliance. [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] Immediate Retransplantation for Pancreas Allograft ThrombosisAMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2009E. F. Hollinger Early pancreas allograft failure most commonly results from thrombosis and requires immediate allograft pancreatectomy. Optimal timing for retransplantation remains undefined. Immediate retransplantation facilitates reuse of the same anatomic site before extensive adhesions have formed. Some studies suggest that early retransplantation is associated with a higher incidence of graft loss. This study is a retrospective review of immediate pancreas retransplants performed at a single center. All cases of pancreas allograft loss within 2 weeks were examined. Of 228 pancreas transplants, 12 grafts were lost within 2 weeks of surgery. Eleven of these underwent allograft pancreatectomy for thrombosis. One suffered anoxic brain injury and was not a retransplantation candidate, one was retransplanted at 3.5 months and nine patients underwent retransplantation 1,16 days following the original transplant. Of the nine early retransplants, one pancreas was lost to heparin-induced thrombocytopenia, one recipient died with function at 2.9 years and the other grafts continue to function at 76,1137 days (mean 572 days). One-year graft survival for early retransplantation was 89% compared to 91% for all pancreas transplants at our center. Immediate retransplantation following pancreatic graft thrombosis restores durable allograft function with outcomes comparable to first-time pancreas transplantation. [source] Renal Allografts with IF/TA Display Distinct Expression Profiles of Metzincins and Related GenesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009S. Rödder Chronic renal allograft injury is often reflected by interstitial fibrosis (IF) and tubular atrophy (TA) without evidence of specific etiology. In most instances, IF/TA remains an irreversible disorder, representing a major cause of long-term allograft loss. As members of the protease family metzincins and functionally related genes are involved in fibrotic and sclerotic processes of the extracellular matrix (ECM), we hypothesized their deregulation in IF/TA. Gene expression and protein level analyses using allograft biopsies with and without Banff'05 classified IF/TA illustrated their deregulation. Expression profiles of these genes differentiated IF/TA from Banff'05 classified Normal biopsies in three independent microarray studies and demonstrated histological progression of IF/TA I to III. Significant upregulation of matrix metalloprotease-7 (MMP-7) and thrombospondin-2 (THBS-2) in IF/TA biopsies and sera was revealed in two independent patient sets. Furthermore, elevated THBS-2, osteopontin (SPP1) and ,-catenin may play regulatory roles on MMP. Our findings further suggest that deregulated ECM remodeling and possibly epithelial to mesenchymal transition (EMT) are implicated in IF/TA of kidney transplants, and that metzincins and related genes play an important role in these processes. Profiling of these genes may be used to complement IF/TA diagnosis and to disclose IF/TA progression in kidney transplant recipients. [source] Identifying Specific Causes of Kidney Allograft LossAMERICAN JOURNAL OF TRANSPLANTATION, Issue 3 2009Z. M. El-Zoghby The causes of kidney allograft loss remain unclear. Herein we investigated these causes in 1317 conventional kidney recipients. The cause of graft loss was determined by reviewing clinical and histologic information the latter available in 98% of cases. During 50.3 ± 32.6 months of follow-up, 330 grafts were lost (25.0%), 138 (10.4%) due to death with function, 39 (2.9%) due to primary nonfunction and 153 (11.6%) due to graft failure censored for death. The latter group was subdivided by cause into: glomerular diseases (n = 56, 36.6%); fibrosis/atrophy (n = 47, 30.7%); medical/surgical conditions (n = 25, 16.3%); acute rejection (n = 18, 11.8%); and unclassifiable (n = 7, 4.6%). Glomerular pathologies leading to failure included recurrent disease (n = 23), transplant glomerulopathy (n = 23) and presumed nonrecurrent disease (n = 10). In cases with fibrosis/atrophy a specific cause(s) was identified in 81% and it was rarely attributable to calcineurin inhibitor (CNI) toxicity alone (n = 1, 0.7%). Contrary to current concepts, most cases of kidney graft loss have an identifiable cause that is not idiopathic fibrosis/atrophy or CNI toxicity. Glomerular pathologies cause the largest proportion of graft loss and alloinmunity remains the most common mechanism leading to failure. This study identifies targets for investigation and intervention that may result in improved kidney transplantation outcomes. [source] Prolonged Survival of Allogeneic Islets in Cynomolgus Monkeys After Short-Term Anti-CD154-Based Therapy: Nonimmunologic Graft Failure?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2006M. Koulmanda Conventional drug therapy and several anti-CD154 mAb-based regimens were tested in the nonhuman primate (NHP) islet allograft model and found to be inadequate because islets were lost to rejection. Short-term therapy with an optimized donor-specific transfusion (DST) + rapamycin (RPM) + anti-CD154 mAb regimen enables immunosuppression drug-free islet allograft function for months following cessation of therapy in the NHP islet allograft model. After a substantial period of drug-free graft function, these allografts slowly and progressively lost function. Pathologic studies failed to identify islet allograft rejection as a destructive islet invasive lymphocytic infiltration of the allograft was not detected. To evaluate the mechanism, immunologic versus nonimmunologic, of the late islet allograft loss in hosts receiving the optimized therapeutic regimen, we performed experiments with islet autografts and studied islet function in NHPs with partial pancreatectomy. The results in both experiments utilizing autologous islet allografts and partially pancreatectomized hosts reinforce the view that the presence of a marginal islet mass leads to slowly progressive nonimmunological islet loss. Long-term clinically successful islet cell transplantation cannot be realized in the absence of parallel improvements in tolerizing regimens and in the preparation of adequate numbers of islets. [source] Screening to Prevent Polyoma Virus Nephropathy: A Medical Decision AnalysisAMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2005Bryce A Kiberd Polyomavirus nephropathy (PVN) is an emerging medical dilemma in kidney transplantation. Methods to screen before clinical disease are available and early immunosuppression reduction may change the natural history of progression. However, the consequences of an increase in rejection may limit the benefits. In a simulation model a 'screen' versus 'no-screen' strategy was compared. Baseline PVN cumulative incidence was assumed to be 4%. Patients with PVN were modeled to have 4-fold higher risk of graft loss. In the screen strategy, patients positive for blood DNA PCR had their immunosuppression reduced. This pre-emptive change was modeled to reduce progression to overt PVN by 80%. Therapy reduction was associated with a 10% risk of precipitating acute rejection and greater risk of chronic allograft loss. In the baseline case, screening saved $1912 (discounted) and produced 0.020 more quality adjusted life years (QALYs) than not screening. Screening resulted in decreased net QALYs if the false positive viremia rate was >9.5% and the PVN incidence was <2.1%. Much of the cost savings of screening relate to savings from immunosuppression reduction in the screened arm. Screening may well be cost-effective if not cost saving in centers with high PVN rates. There remain significant areas of uncertainty. [source] Risk factors and impact of recurrent lupus nephritis in patients with systemic lupus erythematosus undergoing renal transplantation: Data from a single US institutionARTHRITIS & RHEUMATISM, Issue 9 2009Paula I. Burgos Objective To determine the risk factors for recurrent lupus nephritis, allograft loss, and survival among patients with systemic lupus erythematosus (SLE) undergoing kidney transplantation. Methods The archival records of all kidney transplant recipients with a prior diagnosis of SLE (according to the American College of Rheumatology criteria) from June 1977 to June 2007 were reviewed. Patients who had died or lost the allograft within 90 days of engraftment were excluded. Time-to-event data were examined by univariable and multivariable Cox proportional hazards regression analyses. Results Two hundred twenty of nearly 7,000 renal transplantations were performed in 202 SLE patients during the 30-year interval. Of the 177 patients who met the criteria for study entry, the majority were women (80%) and African American (65%), the mean age was 35.6 years, and the mean disease duration was 11.2 years. Recurrent lupus nephritis was noted in 20 patients (11%), allograft loss in 69 patients (39%), and death in 36 patients (20%). African American ethnicity was found to be associated with a shorter time-to-event for recurrent lupus nephritis (hazard ratio [HR] 4.63, 95% confidence interval [95% CI] 1.29,16.65) and death (HR 2.47, 95% CI 0.91,6.71), although, with the latter, the association was not statistically significant. Recurrent lupus nephritis and chronic rejection of the kidney transplant were found to be risk factors for allograft loss (HR 2.48, 95% CI 1.09,5.60 and HR 2.72, 95% CI 1.55,4.78, respectively). In patients with recurrent lupus nephritis, the lesion in the engrafted kidney was predominantly mesangial, compared with a predominance of proliferative or membranous lesions in the native kidneys. Conclusion African American ethnicity was independently associated with recurrent lupus nephritis. Allograft loss was associated with chronic transplant rejection and recurrence of lupus nephritis. Recurrent lupus nephritis is infrequent and relatively benign, without influence on a patient's survival. [source] Disruption of Murine Cardiac Allograft Acceptance by Latent CytomegalovirusAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009C. H. Cook Cytomegalovirus (CMV) reactivation is a well-described complication of solid organ transplantation. These studies were performed to (1) determine if cardiac allograft transplantation of latently infected recipients results in reactivation of CMV and (2) determine what impact CMV might have on development of graft acceptance/tolerance. BALB/c cardiac allografts were transplanted into C57BL/6 mice with/without latent murine CMV (MCMV). Recipients were treated with gallium nitrate induction and monitored for graft survival, viral immunity and donor reactive DTH responses. Latently infected allograft recipients had ,80% graft loss by 100 days after transplant, compared with ,8% graft loss in naïve recipients. PCR evaluation demonstrated that MCMV was transmitted to cardiac grafts in all latently infected recipients, and 4/8 allografts had active viral transcription compared to 0/6 isografts. Latently infected allograft recipients showed intragraft IFN-, expression consistent with MCMV reactivation, but MCMV did not appear to negatively influence regulatory gene expression. Infected allograft recipients had disruption of splenocyte DTH regulation, but recipient splenocytes remained unresponsive to donor antigen even after allograft losses. These data suggest that transplantation in an environment of latent CMV infection may reactivate virus, and that intragraft responses disrupt development of allograft acceptance. [source] | ||||||||||