Home  About us  Contact
 

Maintenance Immunosuppression (maintenance + immunosuppression)

Distribution by Scientific Domains
Medical Sciences100%

Kinds of Maintenance Immunosuppression

  • steroid-free maintenance immunosuppression
    		•

    Selected Abstracts

    Alemtuzumab Induction Prior to Cardiac Transplantation with Lower Intensity Maintenance Immunosuppression: One-Year Outcomes

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010
    J. J. Teuteberg
    Induction therapy with alemtuzumab (C-1H) prior to cardiac transplantation (CTX) may allow for lower intensity maintenance immunosuppression. This is a retrospective study of patients who underwent CTX at a single institution from January 2001 until April 2009 and received no induction versus induction with C-1H on a background of tacrolimus and mycophenolate. Those with C-1H received dose-reduced calcineurin inhibitor and no steroids. A total of 220 patients were included, 110 received C-1H and 110 received no induction. Recipient baseline characteristics, donor age and gender were not different between the two groups. Mean tacrolimus levels (ng/mL) for C-1H versus no induction: months 1,3 (8.5 vs. 12.9), month 4,6 (10.2 vs. 13.0), month 7,9 (10.2 vs. 11.9) and month 10,12 (9.9 vs. 11.3) were all significantly lower for the C-1H group, p < 0.001. There were no differences between the C-1H and no induction groups at 12 months for overall survival 85.1% versus 93.6% p = 0.09, but freedom from significant rejection was significantly higher for the C-1H group, 84.5% versus 51.6%, p < 0.0001. In conclusion, induction therapy after CTX with C-1H results in a similar 12 month survival, but a greater freedom from rejection despite lower calcineurin levels and without the use of steroids. [source]

    Belatacept as Maintenance Immunosuppression for Postrenal Transplant de novo Drug-Induced Thrombotic Microangiopathy

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2009
    N. Ashman
    De novo posttransplant thrombotic microangiopathy (TMA) is a complication of solid organ transplantation, which remains difficult to treat. In many cases, immunosuppressants and particularly calcineurin inhibitors, trigger TMA. Although withdrawing the offending drug may lead to resolution of TMA, graft and patient outcomes are poor. Specific treatments, including plasma exchange, have not gained widespread acceptance in those with fulminant disease and new approaches to the condition are urgently needed. We report a case of posttransplant de novo TMA presenting serially in association with ciclosporin, tacrolimus and sirolimus in a young recipient of a living donor kidney transplant. We describe a patient treated with belatacept, a novel CTLA4 Ig fusion protein, as ongoing maintenance immunosuppression to allow avoidance of conventional agents once associated with TMA. We report excellent early graft outcome, with no adverse events using this strategy. We suggest that belatacept may have a role in this traditionally difficult-to-treat group of patients. [source]

    Graft and Patient Survival in Kidney Transplant Recipients Selected for de novo Steroid-Free Maintenance Immunosuppression

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2009
    F. L. Luan
    Steroid-free regimen is increasingly employed in kidney transplant recipients across transplant centers. However, concern remains because of the unknown impact of such an approach on long-term graft and patient survival. We studied the outcomes of steroid-free immunosuppression in a population-based U.S. cohort of kidney transplant recipients. All adult solitary kidney transplant recipients engrafted between January 1, 2000 and December 31, 2006 were stratified according to whether they were selected for a steroid-free or steroid-containing regimen at discharge. Multivariate Cox regression models were used to estimate graft and patient survival. The impact of the practice pattern on steroid use at individual transplant centers was analyzed. Among 95 755 kidney transplant recipients, 17.2% were steroid-free at discharge (n = 16 491). Selection for a steroid-free regimen was associated with reduced risks for graft failure and death at 1 year (HR 0.78, 95% CI 0.72,0.85, and HR 0.73, 95% CI 0.65,0.82, respectively, p < 0.0001) and 4 years (HR 0.83, 95% CI 0.78,0.87, and HR 0.76, 95% CI 0.71,0.83, respectively, p < 0.0001). This association was mostly observed at individual centers where less than 65% of recipients were discharged on the steroid-containing regimen. De novo steroid-free immunosuppression as currently practiced in the United States appears to carry no increased risk of adverse clinical outcomes in the intermediate term. [source]

    Prednisone-Free Maintenance Immunosuppression,A 5-Year Experience

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2005
    Arthur 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]

    Thymoglobulin-Associated Cd4+ T-Cell Depletion and Infection Risk in HIV-Infected Renal Transplant Recipients

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2006
    J.T. Carter
    HIV-infected patients are increasingly referred for kidney transplantation, and may be at an increased risk for rejection. Treatment for rejection frequently includes thymoglobulin. We studied thymoglobulin's effect on CD4+ T-cell count, risk of infection and rejection reversal in 20 consecutive HIV-infected kidney recipients. All patients used antiretroviral therapy and opportunistic infection prophylaxis. Maintenance immunosuppression consisted of prednisone, mycophenolate mofetil and cyclosporine. Eleven patients received thymoglobulin (7 for rejection and 4 for delayed/slow graft function) while 9 did not. These two groups were similar in age, gender, race, donor characteristics and immunosuppression. Mean CD4+ T-cell counts remained stable in patients who did not receive thymoglobulin, but became profoundly suppressed in those who did, decreasing from 475 ± 192 to 9 ± 10 cells/,L (p < 0.001). Recovery time ranged from 3 weeks to 2 years despite effective HIV suppression. Although opportunistic infections were successfully suppressed, low CD4+ T-cell count was associated with increased risk of serious infections requiring hospitalization. Rejection reversed in 6 of 7 patients receiving thymoglobulin. We conclude that thymoglobulin reverses acute rejection in HIV-infected kidney recipients, but produces profound and long-lasting suppression of the CD4+ T-cell count associated with increased risk of infections requiring hospitalization. [source]

    Conversion to Sirolimus in Renal Transplant Recipients: A Single-Center Experience

    ARTIFICIAL ORGANS, Issue 8 2010
    Berna Yelken
    Abstract Maintenance immunosuppression with calcineurin inhibitors (CNI) following renal transplantation is associated with nephrotoxicity and accelerated graft loss. Sirolimus (SRL) is a nonnephrotoxic immunosuppressive agent. We retrospectively analyzed our experience with kidney transplant recipients who were converted from CNI to SRL. A total of 58 renal transplant recipients were converted from CNI to SRL. SRL was started at a dose of 0.075 mg/kg and, at the same time, CNI dose was reduced by 50% daily for 3 days. SRL trough levels were targeted between 8 and 12 ng/mL. When target trough levels were achieved, CNI was withdrawn. The main indications for switching were posttransplant malignancies (n = 32) and chronic allograft nephropathy (CAN) (n = 10). The mean time from transplantation to conversion was 84 ± 71 months. Mean serum creatinine level was 1.63 ± 0.52 mg/dL before conversion. Serum creatinine levels at the 1, 3, 6 months, and 1, 2, 3 years after conversion were 1.64 ± 0.58 mg/dL (P = 0.67), 1.52 ± 0.53 mg/dL (P = 0.414), 1.62 ± 0.62 mg/dL (P = 0.734), and 1.48 ± 0.58 mg/dL (P = 0.065), 1.58 ± 0.53 mg/dL (P = 0.854), 1.88 ± 0.77 mg/dL (P = 0.083), respectively. Daily proteinuria levels increased from 0.04 ± 0.11 g/day at baseline to 0.55 ± 1.33 g/day (P = 0.037) after conversion, in the responders group. In the nonresponders group, baseline proteinuria was 0.13 ± 0.25 g/day, and increased to 1.44 ± 2.44 g/day after conversion (P = 0.008). SRL was discontinued in 16 patients (31%) because of the occurrence of severe side effects. The proportion of patients remaining on SRL therapy over time was 43.1% at 1 year, 15.5% at 2 years after conversion, and 10.3% at 3 years after conversion. SRL conversion may be very useful in patients suffering from neoplasia; however, frequent side effects related with this intervention should be considered, and routine conversion from CNI to SRL to reduce nephrotoxicity should be discouraged. [source]

    Natural history of clinically compensated hepatitis C virus,related graft cirrhosis after liver transplantation

    HEPATOLOGY, Issue 4 2000
    Marina Berenguer
    The natural history of clinically compensated hepatitis C virus (HCV) cirrhosis after liver transplantation is unknown. This information is relevant to transplant centers to improve the management of these patients and decide the optimal timing for retransplantation. The aims of the study were (1) to describe the natural history of patients with HCV-cirrhosis transplants in a center with annual liver biopsies, and (2) to determine predictors for clinical decompensation, retransplantation, and mortality rates. A total of 49 patients with HCV-graft cirrhosis, 39 clinically compensated at histologic diagnosis of cirrhosis (post,liver transplantation cirrhosis) were included and followed up for 1 year (15 days-3.5 years). All patients tested were infected with genotype 1b. Predictive variables included histologic activity index (HAI) at post,liver transplantation cirrhosis, liver function tests, age, sex, and maintenance immunosuppression. Eighteen of 39 patients developed at least 1 episode of decompensation after a median of 7.8 months (4 days-2.6 years; 93% ascites). The cumulative probability of decompensation was 8%, 17%, and 42% at 1, 6, and 12 months, respectively. Graft and patient survival rates were 100%, 85%, and 71% and 100%, 92%, and 74% at 1, 6, and 12 months, respectively. Patient survival rates dropped significantly once decompensation developed (93%, 61%, and 41% at 1, 6, and 12 months, respectively). Variables associated with decompensation, retransplantation, and mortality rate included a high Child-Pugh score (>A), low levels of albumin at post,liver transplantation cirrhosis, and a short interval between liver transplantation and post,liver transplantation cirrhosis. The natural history of clinically compensated HCV-graft cirrhosis is shortened when compared with immunocompetent patients. If retransplantation is considered, it should be performed promptly once decompensation develops. [source]

    Idiopathic colitis following cardiac transplantation: Three pediatric cases

    PEDIATRIC TRANSPLANTATION, Issue 6 2003
    Ghassan Wahbeh
    Abstract:, Colitis can cause significant morbidity in pediatric solid organ transplant recipients. In many cases, despite intensive evaluation, a specific infectious, inflammatory, or immunologic etiology is not identified, and idiopathic colitis may be the ultimate diagnosis. We defined idiopathic colitis as the presence of gastrointestinal symptoms (vomiting, diarrhea, abdominal pain) with inflammatory changes seen on intestinal biopsy in the absence of identifiable bowel disease. We describe three cases of idiopathic colitis following cardiac transplantation. In each case, the post-transplant course was complicated by persistent abdominal pain, diarrhea, and in two cases, vomiting. All three patients' post-transplant courses were marked by multiple graft rejection episodes, and all received intensified immune therapy in addition to usual maintenance immunosuppression. Differential diagnosis of the patients' gastrointestinal symptoms included drug side effect, indolent opportunistic infections, inflammatory bowel disease, post-transplant lymphoproliferative disease, and microvascular ischemic colitis. Continued symptoms led these patients to extensive evaluation including imaging studies, endoscopy and tissue biopsy, and stool, blood and tissue cultures for viral, bacterial and parasitic pathogens. Definitive differentiation presented significant diagnostic challenge, and once identifiable etiologies were excluded, the diagnosis of idiopathic colitis was assigned. We conclude that idiopathic colitis following pediatric cardiac transplantation can be a cause of significant morbidity. Endoscopic evaluation of patients who present with gastrointestinal symptoms after transplant is warranted to identify the presence of idiopathic colitis once common causes are ruled out. Further study is needed to identify its incidence, etiology, therapeutic options and prognosis. [source]

    Alemtuzumab Induction Prior to Cardiac Transplantation with Lower Intensity Maintenance Immunosuppression: One-Year Outcomes

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010
    J. J. Teuteberg
    Induction therapy with alemtuzumab (C-1H) prior to cardiac transplantation (CTX) may allow for lower intensity maintenance immunosuppression. This is a retrospective study of patients who underwent CTX at a single institution from January 2001 until April 2009 and received no induction versus induction with C-1H on a background of tacrolimus and mycophenolate. Those with C-1H received dose-reduced calcineurin inhibitor and no steroids. A total of 220 patients were included, 110 received C-1H and 110 received no induction. Recipient baseline characteristics, donor age and gender were not different between the two groups. Mean tacrolimus levels (ng/mL) for C-1H versus no induction: months 1,3 (8.5 vs. 12.9), month 4,6 (10.2 vs. 13.0), month 7,9 (10.2 vs. 11.9) and month 10,12 (9.9 vs. 11.3) were all significantly lower for the C-1H group, p < 0.001. There were no differences between the C-1H and no induction groups at 12 months for overall survival 85.1% versus 93.6% p = 0.09, but freedom from significant rejection was significantly higher for the C-1H group, 84.5% versus 51.6%, p < 0.0001. In conclusion, induction therapy after CTX with C-1H results in a similar 12 month survival, but a greater freedom from rejection despite lower calcineurin levels and without the use of steroids. [source]

    Mycophenolate Mofetil and Calcineurin-Inhibitor Reduction: Recent Progress

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009
    Josep M. Grinyó
    Mycophenolate mofetil (MMF) in combination with calcineurin inhibitors (CNIs) has greatly contributed to acute rejection rate reduction. Because of its immunosuppressive potency it was initially thought that MMF would help in reducing/avoiding CNI-related nephrotoxicity. Elective avoidance of CNI in induction and maintenance MMF-based immunosuppression has resulted in an increased risk for acute and chronic rejection. A recent meta-analysis suggests that CNI elimination in patients on MMF with progressive renal dysfunction is associated with a better outcome, although more data are needed to support any recommendation. So far, the more conservative approach involving CNI minimization with MMF has been associated with amelioration of renal function and low risk for rejection, providing an adequate risk/benefit balance. However, MMF with belatacept might pave the way for CNI-free induction and maintenance immunosuppression. Meanwhile, the assessment of immunological risk by new monitoring tools could be a prerequisite to further implement such CNI sparing strategies. [source]

    Belatacept as Maintenance Immunosuppression for Postrenal Transplant de novo Drug-Induced Thrombotic Microangiopathy

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2009
    N. Ashman
    De novo posttransplant thrombotic microangiopathy (TMA) is a complication of solid organ transplantation, which remains difficult to treat. In many cases, immunosuppressants and particularly calcineurin inhibitors, trigger TMA. Although withdrawing the offending drug may lead to resolution of TMA, graft and patient outcomes are poor. Specific treatments, including plasma exchange, have not gained widespread acceptance in those with fulminant disease and new approaches to the condition are urgently needed. We report a case of posttransplant de novo TMA presenting serially in association with ciclosporin, tacrolimus and sirolimus in a young recipient of a living donor kidney transplant. We describe a patient treated with belatacept, a novel CTLA4 Ig fusion protein, as ongoing maintenance immunosuppression to allow avoidance of conventional agents once associated with TMA. We report excellent early graft outcome, with no adverse events using this strategy. We suggest that belatacept may have a role in this traditionally difficult-to-treat group of patients. [source]

    Prolonged Insulin Independence After Islet Allotransplants in Recipients with Type 1 Diabetes

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2008
    M. D. Bellin
    We sought to determine the long-term outcomes in type 1 diabetic recipients of intraportal alloislet transplants on a modified immunosuppressive protocol. Six recipients with hypoglycemia unawareness received one to two islet infusions. Induction therapy was with antithymocyte globulin (ATG) plus etanercept for tumor necrosis factor-, blockade. Recipients received cyclosporine and everolimus for maintenance immunosuppression for the first year posttransplant, with mycophenolic acid or mycophenolate mofetil subsequently substituted for everolimus. Recipients have been followed for 1173 ± 270 days since their last infusion for islet graft function (insulin independence, hemoglobin A1c levels and C-peptide production) and for adverse events associated with the study protocol. Of the six recipients, five were insulin-independent at 1 year, and four continue to be insulin-independent at a mean of 3.4 ± 0.4 years posttransplant. None of the six recipients experienced recurrence of severe hypoglycemia. Measured glomerular filtration rate decreased from 110.5 ± 21.2 mL/min/1.73 m2 pretransplant to 82.6 ±19.1 mL/min/1.73 m2 at 1 year posttransplant. In conclusion, islet transplants restored insulin independence for a mean of >3 years in four of six recipients treated with ATG and etanercept induction therapy and with cyclosporine and, initially, everolimus for maintenance. Our results suggest this immunosuppressive protocol may allow long-term graft survival. [source]

    CD4+CD25+FOXP3+ Regulatory T Cells Increase De Novo in Kidney Transplant Patients After Immunodepletion with Campath-1H

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2008
    D. D. Bloom
    Campath-1H (Alemtuzumab) is an effective immunodepletion agent used in renal transplantation. To evaluate its influence on T lymphocytes during repletion, we analyzed peripheral blood from Campath-1H-treated renal allograft recipients for the presence of FOXP3+ regulatory T (Treg) cells. Flow cytometry demonstrated that CD4+CD25+FOXP3+ lymphocytes increased significantly within the CD4+ T-cell population, skewing Treg/Teff (T effector) ratios for up to several years. In contrast, Treg levels in patients treated with anti-CD25 (Basiliximab) and maintained on CsA demonstrated a sustained decrease. The increase in Tregs in Campath-1H treated patients developed independent of maintenance immunosuppression. Importantly, the increase in Tregs was not fully explained by their homeostatic proliferation, increased thymic output, or Treg sparing, suggesting de novo generation/expansion. Consistent with this, in vitro stimulation of PBMCs with Campath-1H, with or without anti-CD3, activation led to an increase in CD4+CD25+FOXP3+ cells that had suppressive capabilities. Together, these data suggest that Campath-1H promotes an increase in peripheral Tregs and may act as an intrinsic generator of Tregs in vivo. [source]

    Homeostatic Repopulation by CD28,CD8+ T Cells in Alemtuzumab-Depleted Kidney Transplant Recipients Treated With Reduced Immunosuppression

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2008
    P. Trzonkowski
    Alemtuzumab (CAMPATH-1H) is a depleting agent introduced recently in transplantation and often used with reduced maintenance immunosuppression. In the current study we investigated the immune response of 13 kidney allograft recipients treated with alemtuzumab followed by weaned immunosuppression with reduced dose of mycophenolate mofetil (MMF) and tacrolimus. Tacrolimus was switched to sirolimus at 6 months and MMF withdrawn at 12 months after transplantation. We found that after alemtuzumab induction the recovery of CD8+ T cells was much faster than that of CD4+ T cells. It was complete 6 months posttransplant while CD4+ T cells did not fully recover even 15 months posttransplant. Repopulating CD8+ T cells were mainly of immunosenescent CD28,CD8+ phenotype. In a series of in vitro experiments we showed that CD28,CD8+ T cells might suppress proliferation of CD4+ T cells. There were three successfully treated acute rejections during the study (first at +70 day, two others +12 months) that occurred in patients with the lowest level of CD28,CD8+ T cells. We hypothesize that expanded CD28,CD8+ T cells might compete for ,immune space' with CD4+ T cells suppressing their proliferation and therefore delaying CD4+ T-cells recovery. This delay might be associated with the clinical outcome as CD4+ T cells, notably CD4+ T effector memory cells, were shown to be associated with rejection. [source]

    Prospective Monitoring of Polyomavirus BK Replication and Impact of Pre-Emptive Intervention in Pediatric Kidney Recipients

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2007
    F. Ginevri
    Polyoma BK virus (BKV)-associated nephropathy (PVAN) is a relevant cause of poor renal allograft survival. In a prospective analysis, we monitored BKV DNA in blood and urine samples from 62 consecutive pediatric kidney recipients. In patients with BKV replication, we analyzed the impact of reduction of maintenance immunosuppression on viral load kinetics and PVAN in patients with BKV replication. BKV-specific immunity was concomitantly evaluated on blood samples of viremic patients, by measuring the frequency of BKV-specific interferon-,-producing and cytotoxic T cells, and BKV IgG antibody levels. At a median follow-up of 24 months, BK viruria was observed in 39 of 62 patients, while BK viremia developed in 13 patients (21%). In all viremic patients, immunosuppression reduction resulted in the clearance of viremia, and prevented development of PVAN, without increasing the rate of acute rejection or causing graft dysfunction. As a consequence of immunosuppression adjustment, an expansion of BKV-specific cellular immunity was observed that coincided with viral clearance. We conclude that treating pediatric kidney transplant patients pre-emptively with immunosuppression reduction guided by BKV DNA in blood is safe and effective to prevent onset of PVAN. BKV-specific cellular immunity may be useful to guide this intervention. [source]

    Pretransplant HLA Antibodies Are Associated with Reduced Graft Survival After Clinical Islet Transplantation

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2007
    P. M. Campbell
    Despite significant improvements in islet transplantation, long-term graft function is still not optimal. It is likely that both immune and nonimmune factors are involved in the deterioration of islet function over time. Historically, the pretransplant T-cell crossmatch and antibody screening were done by anti-human globulin,complement-dependent cytotoxicity (AHG-CDC). Class II antibodies were not evaluated. In 2003, we introduced solid-phase antibody screening using flow-based beads and flow crossmatching. We were interested to know whether pretransplant human leukocyte antigen (HLA) antibodies or a positive flow crossmatch impacted islet function post-transplant. A total of 152 islet transplants was performed in 81 patients. Islet function was determined by a positive C-peptide. Results were analyzed by procedure. Class I and class II panel reactive antibody (PRA) > 15% and donor-specific antibodies (DSA) were associated with a reduced C-peptide survival (p < 0.0001 and p < 0.0001, respectively). A positive T- and or B-cell crossmatch alone was not. Pretransplant HLA antibodies detectable by flow beads are associated with reduced graft survival. This suggests that the sirolimus and low-dose tacrolimus-based immunosuppression may not control the alloimmune response in this presensitized population and individuals with a PRA > 15% may require more aggressive inductive and maintenance immunosuppression, or represent a group that may not benefit from islet transplantation. [source]

    Recovery of Functional Memory T Cells in Lung Transplant Recipients Following Induction Therapy with Alemtuzumab

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2007
    A. Zeevi
    Profound T-cell depletion with the monoclonal antibody alemtuzumab facilitates reduced maintenance immunosuppression in abdominal and lung transplantation. While the phenotype of the post-depletional T cells has been characterized, little is known about their function. In the present study, global and CMV-specific T-cell function was assessed longitudinally in 23 lung transplant (LTx) recipients using T-cell assays (ImmuKnow® and T Cell MemoryÔ, Cylex, Columbia, MD) during the first year posttransplant after induction therapy. Recovery of mitogen responses were seen at 2 weeks posttransplantation (65%PHA; 58% Con A), despite the low number of circulating T cells (<2%). These responses declined at 4,5 months (24%PHA; 54% Con A) and were partially reconstituted by 9 months (46% PHA; 73% Con A). CMV-specific responses recovered in 80% of R+ patients as early as 2 weeks posttransplant (n = 5) and 72% of patients had a memory response by 3 months (n = 11). In contrast, only 2 of 5 patients who did not exhibit memory responses pre-transplant (R,) developed transient CMV-specific T-cell responses. Our results show that profound depletion of T cells induced by alemtuzumab spares the functional subset of CMV-specific memory T cells. Conversely, CMV R, patients predepletion may require a prolonged period of prophylaxis. [source]

    Prednisone-Free Maintenance Immunosuppression,A 5-Year Experience

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 10 2005
    Arthur 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]

    Evaluation of T-Cell Receptor Repertoires in Patients with Long-Term Renal Allograft Survival

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 4 2005
    Cristiam M. Alvarez
    The mechanisms underlying long-term acceptance of kidney allografts in humans under minimal or no maintenance immunosuppression are poorly understood. We analyzed the T-cell receptor (TCR) repertoires in circulating T cells of patients with long-term (,9 years) renal allograft survival with (LTS-IS) and without immunosuppression (LTS-NoIS). T cells of LTS patients exhibited strongly altered TCR Vß usage, including an increased frequency of oligoclonality and a decreased frequency of polyclonality. All 3 LTS-NoIS and 12 of 16 LTS-IS patients demonstrated oligoclonality in at least three or more TCR Vß families, and the frequency of oligoclonality in these patients was significantly higher as compared to patients with well-functioning grafts at 3 years (p < 0.005 both), an uncomplicated course during the first year (p < 0.0001, both), acute rejection (p < 0.0001, both), chronic allograft nephropathy at 7 (p < 0.0001, both) or 13 years (p < 0.0001, both), dialysis patients (p < 0.0001, both) or healthy controls (p < 0.0001, both). In contrast to LTS patients, all other studied patient groups exhibited a polyclonal TCR repertoire. Our data indicate that TCR alteration is a common feature of long-term allograft outcome, which might be explained by clonal deletion, exhaustion of alloreactive T cells or predominant expression of particular T-cell subpopulations, such as regulatory T cells. [source]

    Dendritic Cell Subset Ratio in Peripheral Blood Correlates with Successful Withdrawal of Immunosuppression in Liver Transplant Patients

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2003
    George V. Mazariegos
    Human dendritic cell (DC) subsets appear to play distinct roles in the induction and regulation of immune responses. While monocytoid DC (DC1) induce T-helper (Th) 1-type responses, plasmacytoid DC (DC2) have been reported to selectively induce Th2 responses. In blood, their precursors (p) can be identified as HLA-DR+ lineage, cells that are further characterized as CD11c+ CD123,/lo (IL-3R,,/lo) (pDC1) or as CD11c, CD123hi (pDC2) by rare event, flow cytometric analysis. We compared the incidences of pDC1 and pDC2 in peripheral blood mononuclear cell populations isolated from normal healthy controls and from 3 groups of clinically stable liver transplant patients. Group A had been successfully withdrawn from immunosuppression, whereas group B were undergoing prospective drug weaning and on minimal anti-rejection therapy. In group C, drug withdrawal had either failed or never been attempted and patients were on maintenance immunosuppression. Assessment of DC subsets and the pDC2 : pDC1 ratio showed good intra-and interassay reproducibility. Compared with patients in group C, those in groups A and B demonstrated a significantly higher relative incidence of pDC2 and a lower incidence of pDC1 , similar to those values observed in normal healthy controls. Moreover, the pDC2 : pDC1 ratio was significantly higher in patients undergoing (successful) weaning and in those off immunosuppression compared with patients on maintenance immunosuppression. [source]

    Lower risk of urinary tract infection with low-dose trimethoprim/sulfamethoxazole compared to dapsone prophylaxis in older renal transplant patients on a rapid steroid-withdrawal immunosuppression regimen

    CLINICAL TRANSPLANTATION, Issue 5 2010
    Jeffrey Allen Giullian
    Giullian JA, Cavanaugh K, Schaefer H. Lower risk of urinary tract infection with low-dose trimethoprim/sulfamethoxazole compared to dapsone prophylaxis in older renal transplant patients on a rapid steroid-withdrawal immunosuppression regimen. Clin Transplant 2009 DOI: 10.1111/j.1399-0012.2009.01129.x © 2009 John Wiley & Sons A/S. Abstract:, Background:, Urinary tract infections (UTI) are common in renal transplant recipients. Trimethoprim/sulfamethoxazole (TMP/SMZ) in moderate to high daily doses prevents Pneumocystis jiroveci (PCP) and reduces the risk of UTI in renal transplant patients. Low-dose TMP/SMZ also reduces the risk of PCP, although its ability to reduce the risk of UTI is uncertain. Design:, Retrospective review of 158 patients who received a renal transplant without corticosteroids for maintenance immunosuppression. Results:, Forty percent of patients initially prescribed TMP/SMZ ultimately stopped this medication early because of an adverse reaction. Urinary infection occurred in 16% without a significant difference in the risk of UTI between those treated with dapsone vs. those treated with TMP/SMZ (HR [95%CI]: 1.7 [0.75, 3.9], p = 0.2). In the subset of patients who were older than age 47 yr (mean age for this cohort, SD ± 6.2 yr), those treated with dapsone originally or who switched from TMP/SMZ to dapsone had a greater risk of UTI compared to patients who remained on TMP/SMZ (HR [95%CI]: 4.3 [1.2, 15.5], p = 0.024). Conclusions:, For renal transplant recipients over the age of 47 yr, treated without long-term glucocorticoids, our retrospective data suggest that low-dose TMP/SMZ is associated with a lower risk of UTI compared to dapsone prophylaxis. [source]

    Obesity following kidney transplantation and steroid avoidance immunosuppression

    CLINICAL TRANSPLANTATION, Issue 3 2008
    Eric A. Elster
    Abstract:, Obesity is an important co-morbidity within end-stage renal disease (ESRD) and renal transplant populations. Previous studies have suggested that chronic corticosteroids result in increased body weight post-transplant. With the recent adoption of steroid-sparing immunosuppressive strategies, we evaluated the effect of these strategies on body mass index (BMI) after renal transplantation. We examined 95 renal transplant recipients enrolled in National Institutes of Health clinical transplant trials over the past three yr who received either lymphocyte depletion-based steroid sparing or traditional immunosuppressive therapy that included steroids for maintenance immunosuppression. Recipients were overweight prior to transplant and no significant differences existed in pre-transplant BMI among treatment groups. Regardless of therapy, BMI increased post-transplant in all recipients. The BMI increase consisted of an average weight gain of 5.01 ± 7.12 kg (mean, SD) post-transplant. Additionally, in a number of recipients placed on maintenance steroids, subsequent withdrawal at a mean of 100 d post-transplant had no impact on weight gain. Thus, body weight and BMI increase following kidney transplantation, even in the absence of steroids. Thus, patients gain weight after renal transplantation regardless of the treatment strategy. Steroid avoidance alone does not reduce risk factors associated with obesity in our patient population. [source]

    A randomized trial of thymoglobulin vs. alemtuzumab (with lower dose maintenance immunosuppression) vs. daclizumab in renal transplantation at 24 months of follow-up

    CLINICAL TRANSPLANTATION, Issue 2 2008
    Gaetano Ciancio
    Abstract: Introduction: A long-term prospective randomized trial evaluating alemtuzumab, a humanized anti-CD52 monoclonal antibody, in a predominantly non-Caucasian population has yet to be reported. Methods: Ninety deceased donor (DD) first renal transplant recipients were randomized into three different antibody induction groups: group A, thymoglobulin (Thymo); group B, alemtuzumab; group C, daclizumab (Dac). In groups A and C, the target trough levels of tacrolimus were 8,10 ng/mL, mycophenolate mofetil (MMF) 1 g administered twice daily, and maintenance methylprednisolone. In group B, target tacrolimus trough levels were 4,7 ng/mL, 500 mg MMF administered twice-daily, without methylprednisolone. African-Americans and Hispanics comprised more than 50% in each group. Results: A minimum follow-up of 27 months showed no overall group differences in patient or graft survival (p = 0.89 and 0.66), but a trend towards worse death-censored graft survival in group B (p = 0.05). Acute rejection rates were not significantly different: six (20%), seven (23%), and seven (23%) in groups A, B, and C, respectively. The incidence of chronic allograft nephropathy was higher in group B than in A and C (p = 0.008). The mean calculated creatinine clearance at 24 months was 81.1 ± 5.5, 64.4 ± 4.5, and 80.7 ± 5.7 in groups A, B, and C, respectively (p = 0.01 for B vs. average of A and C). Conclusion: In this randomized 27-month minimum follow-up trial of predominantly non-Caucasian DD renal transplant recipients with alemtuzumab induction, lower maintenance tacrolimus, MMF, and steroid avoidance appear less effective than either Thymo or Dac with higher maintenance immunosuppression. [source]

    Excellent clinical outcomes in primary kidney transplant recipients treated with steroid-free maintenance immunosuppression

    CLINICAL TRANSPLANTATION, Issue 5 2006
    Amer Rajab
    Abstract:, Steroid-free maintenance immunosuppression is desirable to eliminate the side effects of chronic corticosteroid use. Complete steroid avoidance or rapid post-transplant steroid withdrawal has recently been used in renal transplant recipients with encouraging results. The present study evaluated the outcome of a steroid-free maintenance immunosuppressive protocol in kidney transplant recipients with at least one-yr follow up. Between April 2002 and October 2004, a total of 301 primary kidney transplant recipients received steroid-free maintenance immunosuppression. The regimen consisted of induction with thymogobulin and prednisone for the first five d. Patients were maintained on Sirolimus and Neoral. Neoral dose was adjusted to target C2 levels and the Sirolimus dose was adjusted to a target rapamycin trough level. All primary kidney transplants (n = 502) performed in the two yr (starting January 2000) prior to institution of the steroid-free regimen and thus maintained on a steroid-based immunosuppressive protocol were used for comparison. One-year patient and death censored graft survival were 93.1% and 98.1% for the steroid-free group vs. 95.2% and 95.2% for the comparator groups (p = ns). The incidence of biopsy-proven acute rejection was 4.9% in the steroid-free group vs. 9.4% in the comparator group (p < 0.01). Two (0.7%) of 301 patients in the steroid-free group lost their grafts because of acute rejection compared with nine (1.8%) patients in the comparator group (p < 0.05). At one-yr post-transplant the mean serum creatinine level was not different between the two groups. There were no significant differences in mean serum cholesterol and triglycerides levels as well as the percentage of patients on lipid lowering agents between the groups. White blood cell counts, daily doses of Neoral and weight gain were significantly lower in the steroid-free group vs. the comparator group. However, more patients in the steroid-free group required erythropoietin and iron therapy for anemia (p < 0.001). We conclude that excellent graft survival with a significantly lower incidence of acute rejection can be achieved using a steroid-free maintenance immunosuppressive protocol consisting of Neoral and Sirolimus. [source]

    Cytomegalovirus prophylaxis with valganciclovir in African,American renal allograft recipients based on donor/recipient serostatus

    CLINICAL TRANSPLANTATION, Issue 2 2005
    Scott A Gruber
    Abstract:, There is a paucity of data examining the efficacy of valganciclovir (VGC) for cytomegalovirus (CMV) prophylaxis in kidney transplant patients, particularly with regard to utilization of a risk-stratified dosing regimen. Eighty adult African,American (AA) renal allograft recipients transplanted from November 3, 2001 to May 28, 2003 and followed for 22 ± 8 months received VGC once daily for 90 d post-transplant dosed according to donor/recipient (D/R) serostatus: high risk (D+/R,) received 900 mg (n = 12); moderate risk (D+/R+, D,/R+) received 450 mg (n = 60); and low risk (D,/R,) received no prophylaxis (n = 8). Thymoglobulin or basiliximab was used for induction, and mycophenolate mofetil, prednisone, and either tacrolimus or sirolimus for maintenance immunosuppression. Only six patients (7.5%) developed symptomatic CMV infection diagnosed by pp65 antigenemia, three in the high-risk (25%) and three in the moderate-risk (5%) group (p = 0.02). All patients were on tacrolimus for at least 3 months prior to diagnosis. There were no cases of tissue-invasive disease, resistance to treatment, or recurrence. D+/R, serostatus was the only significant independent predictor for CMV infection using multivariate analysis (odds ratio 10.5; p = 0.04). Thymoglobulin induction was not associated with CMV infection. None of 43 patients who were exposed to sirolimus for >30 d developed CMV infection, vs. six of 37 who were not (p = 0.006). We conclude that VGC dosed according to D/R serostatus provides safe and effective CMV prophylaxis in AA renal allograft recipients. [source]