scholarly journals Mycophenolate Mofetil Does Not Modify the Incidence of Cytomegalovirus (CMV) Disease after Kidney Transplantation but Prevents CMV-Induced Chronic Graft Dysfunction

2001 ◽  
Vol 12 (8) ◽  
pp. 1758-1763
Author(s):  
MAGALI GIRAL ◽  
JEAN MICHEL NGUYEN ◽  
PASCAL DAGUIN ◽  
MARYVONNE HOURMANT ◽  
DIEGO CANTAROVICH ◽  
...  
Keyword(s):  
Mycophenolate Mofetil ◽  
Acute Rejection ◽  
Graft Survival ◽  
Treated Group ◽  
Graft Dysfunction ◽  
Cmv Infection ◽  
Virus Activity ◽  
Chronic Graft Dysfunction ◽  
Herpès Virus ◽  
Cmv Disease

Abstract. Ganciclovir, which is used to treat cytomegalovirus (CMV) infection, has been shown in rodent models to abolish CMV-mediated chronic cellular damage and endothelial cell proliferation; when associated with mycophenolate mofetil (MMF), it has been shown to increase its anti—herpes virus activity. This study tested the hypothesis that kidney graft recipients who received antirejection prophylaxis with MMF and who were treated with ganciclovir for a declared CMV disease could be protected from chronic graft dysfunction. Investigated was the impact of ganciclovir-treated CMV diseases in consecutive first kidney recipients according to their immunosuppressive therapy. The azathioprine (Aza)-treated group (Aza group) included 319 patients. The MMF-treated group (MMF group) included 126 patients. CMV disease was clinically defined and confirmed by virological proof of CMV infection and was treated for at least 14 d with ganciclovir. Despite having the same incidence (21.6% in the Aza group versus 24.6% in the MMF group) and severity, CMV disease was significantly associated with graft loss independent of acute rejection episodes or other factors when tested in a Cox proportional model in the Aza group only (P < 10-4). It was shown for the first time that patients whose CMV disease is treated with ganciclovir while they are on MMF therapy are protected from the long-term deleterious consequences of CMV disease on graft survival, independent of acute rejection. It is suggested that the enhanced anti—herpes virus activity of ganciclovir by MMF could contribute to this reported effect, which may represent a significant contribution of MMF efficacy to graft survival.

scholarly journals MORPHOLOGICAL STRUCTURE OF LATE RENAL GRAFT DYSFUNCTION AND ITS EFFECT FOR LONG-TERM RESULTS

2018 ◽  
Vol 20 (1) ◽  
pp. 45-54 ◽  
Author(s):  
E. S. Stolyarevich ◽  
T. R. Zhilinskaya ◽  
L. Yu. Artyukhina ◽  
I. G. Kim ◽  
V. A. Zaydenov ◽  
...  
Keyword(s):  
Acute Rejection ◽  
Graft Survival ◽  
Chronic Rejection ◽  
De Novo ◽  
Long Term Results ◽  
Functional Disorders ◽  
Graft Dysfunction ◽  
Tubular Atrophy ◽  
Allograft Dysfunction ◽  
Over Time

Aim:to analyze the frequency of different histological diagnoses and it simpact on graft survival in a cohort of patients with renal allograft dysfunction, and to determine pathology features, infl uencing prognosis.Materials and methods.The data obtained from 1470 biopsies, performed by indication at different time after kidney transplantation (48.8 ± 46.1 months) were analyzed retrospectively according to the Banff 2013 classifi cation. Results.The majority of graft dysfunction episodes were attributed to fi ve causes: acute (26,8%) and chronic (12,4%) rejection; chronic nephrotoxicity of СNI (19,3%), interstitial fi brosis/tubular atrophy (15,8%) and recurrent or de novo glomerulonephritis (10,6%). T-cell-mediated acute rejection and functional disorders were the most often cause of dysfunction during the fi rst year after transplantation (40,5% and 21% respectively) but decreased over time. On the other hand, the frequency of chronic rejection, interstitial fi brosis/tubular atrophy with or without СNI nephrotoxicity and recurrent or de novo glomerulonephritis increased from 13%, 26% and 5,5% at the fi rst year to 26,4%, 35,3% and 22,8% respectively at 8 year after transplantation. Chronic rejection represented a major risk for graft loss – 8-year graft survival did not exceed 5%. The prognosis of acute rejection as well asde novoor recurrent glomerular pathologies was more favorable (38% and 42% respectively). In cases of interstitial fi brosis/tubular atrophy with or without СNI nephrotoxicity 8-year graft survival was slightly lower than in the functional disorders (62% and 76%). In acute rejection prognosis for C4d-positive forms was worse compared to C4d-negative, while in chronic rejection there was no difference between C4d-positive and C4d-negative forms. The features of СNI nephrotoxicity did not infl uence the prognosis of non-specifi c interstitial fi brosis and tubular atrophy.Conclusion.Transplant pathology in patients with allograft dysfunction is heterogeneous and changes over time. Acute and chronic rejection; interstitial fi brosis/tubular atrophy with or without СNI nephrotoxicity and recurrent/de novoglomerular pathology are the most often causes of graft dysfunction, but only rejection (mostly chronic) and glomerular pathology are associated with unfavorable prognosis.

scholarly journals MO012IS IT SAFE TO USE INTERLEUKIN-2 RECEPTOR ANTAGONIST INDUCTION THERAPY IN 2DR MISMATCH RENAL TRANSPLANTS IN TACROLIMUS ERA?

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Hatem Kaies Ibrahim Elsayed Ali ◽  
Ahmed Daoud ◽  
Mahmoud Mohamed ◽  
Karim Soliman
Keyword(s):  
Regression Analysis ◽  
Mycophenolate Mofetil ◽  
Renal Transplant ◽  
Acute Rejection ◽  
Receptor Antagonist ◽  
Graft Survival ◽  
Induction Therapy ◽  
Renal Transplant Recipients ◽  
Transplant Recipients ◽  
Maintenance Immunosuppression

Abstract Background and Aims 2DR HLA mismatch indicates high immunological risk renal transplant. Induction therapy with rabbit Anti-thymocyte Globulin (r-ATG) and IL-2 Receptor Antagonist (IL-2RA) resulted in marked reduction of acute allograft rejection rate and improved graft survival. However, the outcomes in 2DR (HLA-DR) mismatched renal transplant recipients (RTRs) in the era tacrolimus-mycophenolate mofetil maintenance immunosuppression remains understudied. Method Using data from the United States organ procurement and transplantation network, all 2 DR mismatched RTRs with panel reactive antibodies &lt;20% maintained on tacrolimus and mycophenolate mofetil immunotherapy between 2000 and 2017 were retrospectively reviewed. Data including age, sex, gender, ethnicity, functional status, diabetes, body mass index, cold ischemia time, number of previous transplants, panel reactive antibodies, donor type, donor age, HLA-mismatches, number of acute rejection episodes, induction therapies, maintenance immunotherapy, recipients and graft survival were collected. Based on induction therapies administered, RTRs were divided into 2 groups: (r-ATG) and IL-2RA groups. Poisson regression analysis was used to assess effect of induction therapies on acute rejection episodes. Cox hazard regression analysis was used to assess effect of different induction therapies on patient and graft survival Results 3379 patients received IL2-RA while 3677 patients received ATG for induction. There were no significant differences between both groups in terms of acute rejection episodes (95% CI ranges from 0.95 to 1.068, P=0.805), graft survival (95% CI: 0.91 - 1.06, P=0.712), or patient survival (95% CI: -0.949 - 1.12, P=0.43) . Conclusion This study revealed no significant difference in acute rejection episodes, patient or graft survival when utilizing ATG vs IL-2RA in 2DR HLA mismatched renal transplant recipients with PRA&lt;20%, in the tacrolimus-based maintenance immunosuppression era. Therefore, IL2-RA is a safe induction therapy in this group of patients and non-inferior to –ATG induction therapy.

scholarly journals Open Randomized Trial Comparing Early Withdrawal of either Cyclosporine or Mycophenolate Mofetil in Stable Renal Transplant Recipients Initially Treated with a Triple Drug Regimen

2002 ◽  
Vol 13 (2) ◽  
pp. 536-543 ◽  
Author(s):  
Peter Schnuelle ◽  
Jaap Homan van der Heide ◽  
Adam Tegzess ◽  
Cornelis A. Verburgh ◽  
Leendert C. Paul ◽  
...  
Keyword(s):  
Renal Function ◽  
Mycophenolate Mofetil ◽  
Drug Therapy ◽  
Renal Transplant ◽  
Acute Rejection ◽  
Lipid Profile ◽  
Graft Survival ◽  
Drug Regimen ◽  
Renal Transplant Recipients ◽  
Transplant Recipients

ABSTRACT. Cyclosporine (CsA) is the current primary immunosuppressant for the prevention of renal allograft rejection. Its chronic use is associated with various adverse effects like hypertension, hyperlipidemia, and nephrotoxicity, which in turn may contribute to chronic allograft nephropathy and cardiovascular mortality. This study compares a CsA-free maintenance regimen of mycophenolate mofetil (MMF) and corticosteroids with CsA and corticosteroids after early conversion from triple drug therapy. Eighty-four renal transplant recipients who had stable graft function on triple drug therapy with MMF, CsA, and steroids were randomly assigned to be withdrawn from either CsA (n = 44) or MMF (n = 40) at 3 mo posttransplantation. Kidney function at 1 yr was the primary endpoint. Secondary parameters of efficacy were patient and graft survival, incidence of acute rejection episodes, BP, and lipids. At study entry, the alternative treatment groups were similar with respect to demographics, renal function, dosage of CsA, BP, and concomitant medication. Both the creatinine clearance (71.7 versus 60.9 ml/min) and calculated GFR (73.2 versus 61.9 ml/min) were significantly better in MMF-treated patients at 1 yr. Conversion to MMF was associated with a decline of systolic and diastolic BP (128/76 versus 139/82 mmHg) and with a more favorable lipid profile. There was no difference in patient survival (100%) and graft survival (97.7% versus 100%). Acute rejection episodes occurred more frequently after withdrawal of CsA (11.3% versus 5.0%), but the difference was NS. Early tapering of CsA can safely be accomplished in renal transplant recipients who are stable on a triple drug regimen with MMF, thereby resulting in improved renal function, a more favorable lipid profile, and beneficial effects on posttransplant hypertension.

scholarly journals The cost effectiveness of mycophenolate mofetil in the first year after primary cadaveric transplant. U.S. Renal Transplant Mycophenolate Mofetil Study Group.

1997 ◽  
Vol 8 (10) ◽  
pp. 1592-1598 ◽  
Author(s):  
S D Sullivan ◽  
L P Garrison ◽  
J H Best
Keyword(s):  
Mycophenolate Mofetil ◽  
Acute Rejection ◽  
Opportunistic Infection ◽  
Graft Survival ◽  
Rejection Rate ◽  
Treatment Costs ◽  
Sensitivity Analyses ◽  
First Year ◽  
Economic Implications ◽  
The Cost

Mycophenolate mofetil (MMF) has been shown to reduce the incidence of acute graft rejection in three controlled trials of cadaveric renal transplantation. In a U.S. trial using quadruple sequential induction therapy as control, the MMF 2-g treatment group had an acute rejection rate 40.6% lower than control in the first posttransplant year (27.9% MMF-treated versus 47.0% control). The purpose of this analysis is to evaluate the economic implications of these clinical differences. The analysis relies on resource use data from the trial and other sources. Medical costs were estimated using a societal perspective and excluded the cost of the transplant procedure and organ acquisition. The two groups were compared in terms of treatment for acute rejection and opportunistic infection, graft survival, dialysis use, and maintenance immunosuppression. The results suggest that, on average, when compared with standard therapy, patients treated with MMF are likely to have lower rejection-related treatment costs because of a lower incidence of rejection ($6237 versus $3702), lower dialysis and graft failure costs because of improved graft survival ($20,104 versus $16,972), no difference in opportunistic infection treatment costs ($1962 versus $1962), and higher additional immunosuppression costs ($855 versus $5170). Taken together, these results suggest that patients treated with MMF are, on average, likely to have slightly lower first-year costs ($29,158 versus $27,807) compared with control, indicating that MMF treatment is cost-effective in the first year. These results remained stable under sensitivity analyses, with plausible variation in the rates of acute rejection, graft survival, and infection.

scholarly journals P1619OUTCOME OF HIGH DONOR-RECIPIENT AGE GAP IN LIVE-DONOR RENAL TRANSPLANTS IN TACROLIMUS ERA

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Hatem Kaies Ibrahim Elsayed Ali ◽  
Ahmed Daoud ◽  
Karim Soliman ◽  
Mahmoud Mohamed ◽  
Asam Murtaza
Keyword(s):  
Renal Transplant ◽  
Acute Rejection ◽  
Graft Survival ◽  
Age Difference ◽  
Live Donor ◽  
Renal Transplants ◽  
Transplant Patients ◽  
Age Gap ◽  
Group A ◽  
Recipient Age

Abstract Background and Aims High donor-recipient age gap among deceased-donor renal transplant patients leads to worse outcomes. However, the impact of this gap among live-donor renal transplants is unclear. The aim of this study is to assess the effect of this age gap on graft survival and acute rejection rates among renal transplants in tacrolimus era. Method 14390 live-donor renal transplant patients who received a single organ transplant, had no previous renal transplants, discharged on tacrolimus-based immunotherapy and were registered in the Organ Procurement Transplantation Network from January 2000 till June 2017 were included in the study. Donor–recipient age difference was divided into 5 groups; group A (difference &lt;−10,n=4375), group B (difference from -10 to 10,n=7229), group C (difference between 10-20, n=861), group D ( difference between 20–29, n=1406) and group E (difference ≥30 years, n=519). Poisson regression analysis was used to assess effect of age gap on acute rejection rates. Kaplan-Meier survival curves and Cox hazard regression analysis were used to assess this effect on graft survival. Results Regarding graft survival, groups with age difference ≥30 years and between 20-29 years showed a significantly higher risk of graft loss when compared to group with age difference &lt;−10 (HR equals 4.6 and 3.8 respectively). Groups with age difference between 10 to 20 years and between -10 to 10 years showed no significant difference in graft survival when compared to same group (HR equals 1.03 and 0.95 respectively). Groups B,C,D,E were not associated with increased risk of acute rejection episodes when compared to group A (IRR=1.001, 1.001, 1.022, 1.027 respectively). Conclusion Donor-recipient age difference up to 20 years has similar renal transplant outcomes to those receiving kidneys from younger donors and therefore, should not be precluded from paired kidney donation programs. The donor-recipient age difference above 20 years is associated with worse outcomes in terms of graft survival.

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