Abstract:
:Induction and maintenance immunosuppression protocols with or without long-term steroid therapy in kidney transplant recipients are variable and are transplant center-specific. The aim of this prospective randomized pilot study was to compare 5-year outcomes in kidney recipients maintained on 4 different calcineurin inhibitor (CNI)-based immunosuppression protocols without long-term steroid therapy. Two hundred consenting patients who received kidney transplants between June 2000 and October 2004 were enrolled in 4 immunosuppression protocol groups, with 50 patients in each group: cyclosporine (CSA)/mycophenolate mofetil (MMF), CSA/sirolimus (SRL), tacrolimus (TAC)/MMF, and TAC/SRL. Induction therapy was done with basiliximab and methylprednisolone. Steroids were withdrawn on post-transplant day 2, and long-term steroid therapy was not used. Demographic characteristics among the four groups were comparable; approximately 50% of the recipients were African American and > or =80% of the kidneys transplanted were from deceased donors. Clinical acute rejection (CAR) was confirmed by biopsy and treated with intravenous pulse steroid therapy. Steroid-unresponsive CAR was treated with Thymoglobulin. Surveillance biopsies were performed at 1, 6, 12, 24, 36, 48, and 60 months to evaluate subclinical acute rejection (SCAR), chronic allograft injury (CAI), and other pathological changes per the Banff 2005 schema. The primary end point was CAR, and secondary end points were 5-year patient and graft survival rates, renal function, SCAR, CAI, and adverse events. In the first year post-transplant, the incidence of CAR was 18% in the CSA/MMF group, 8% in the CSA/SRL group, 14% in the TAC/MMF group, and 4% in the TAC/SRL group (CSA/MMF vs. TAC/SRL; p=0.05). The incidence of SCAR was 22% in the CSA/MMF group, 8% in the CSA/SRL group, 16% in the TAC/MMF group, and 6% in the TAC/SRL group (CSA/MMF vs. CSA/SRL and TAC/SRL; p=0.05). After the first year, the incidences of CAR and SCAR decreased and were comparable in all 4 groups. At 5 years post-transplant, cumulative CAI due to interstitial fibrosis/tubular atrophy (IF/TA), hypertension (HTN), and chronic calcineurin inhibitor (CNI) toxicity was observed in 54%, 48%, and 8% of the CSA/MMF group vs. 16%, 36%, and 12% of the CSA/SRL group vs. 38%, 24% and 6% of the TAC/MMF group vs. 14%, 25% and 12% of the TAC/SLR group (IF/TA: CSA/MMF vs. CSA/SRL and TAC/SRL; p=0.04, HTN: CSA/MMF vs. TAC/MMF and TAC/SRL; p=0.05, CNI toxicity: TAC/SRL and CSA/SRL vs. TAC/MMF; p=0.05). Five-year patient and graft survival rates were 82% and 60% in the CSA/MMF group, 82% and 60% in the CSA/SRL group, 84% and 62% in the TAC/MMF group, and 82% and 64% in the TAC/SRL group (p=0.9). Serum creatinine levels and creatinine clearances at 5 years were comparable among the groups. Our data show that the rates of CAR and SCAR in the first year post-transplant were significantly lower in the CSA/SRL and TAC/SRL groups and that cumulative CAI rates due to IF/TA and HTN at 5 years were significantly lower in the TAC/MMF, TAC/SRL, and CSA/SRL groups than in the CSA/MMF group. Despite significant differences in the incidences of CAR and SCAR and prevalence of different types of CAI at 5 years, renal function and patient and graft survival rates at 5 years were comparable among kidney recipients maintained on 4 different immunosuppression protocols without long-term steroid therapy.
journal_name
Transpl Immunoljournal_title
Transplant immunologyauthors
Anil Kumar MS,Irfan Saeed M,Ranganna K,Malat G,Sustento-Reodica N,Kumar AM,Meyers WCdoi
10.1016/j.trim.2008.08.005subject
Has Abstractpub_date
2008-11-01 00:00:00pages
32-42issue
1-2eissn
0966-3274issn
1878-5492pii
S0966-3274(08)00074-9journal_volume
20pub_type
杂志文章,随机对照试验abstract:BACKGROUND:Graft-versus-host disease is one of the major complications after allogeneic bone marrow transplantation, but it is not easy to anticipate the onset. Cytokines released by type 1 T helper cells are thought to play a pivotal role in acute graft-versus-host disease aGVHD. The ability to predict the likely occu...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2005.10.002
更新日期:2006-01-01 00:00:00
abstract::B(io) B(reedding)/O(ttawa) K(alsburg) rats spontaneously develop insulin-dependent type 1 diabetes. Days before BB/OK rats become diabetic, their body seems to be flabby which may be attributed to loss of subcutaneous fat. However, the rats are normoglycemic and manifest 3-4 days later. This observation prompted us to...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2011.01.003
更新日期:2011-05-01 00:00:00
abstract::Models of severe combined immuno-deficient (SCID) mice reconstituted with a competent human immune system represent a valuable tool for the study of human immune responses in vivo. Reconstitution with human cells can be achieved using large numbers of peripheral blood lymphocytes, but levels of engraftment are poor an...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2005.07.002
更新日期:2005-12-01 00:00:00
abstract::A rapid and robust limiting dilution assay was developed to measure the frequency of donor-reactive, IL-2 (interleukin 2) producing, helper T lymphocytes in the peripheral T cell population of organ allograft recipients. The IL-2 bioassay was performed using two methodologies to assess the response of CTLL-2 indicator...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/0966-3274(94)90006-x
更新日期:1994-12-01 00:00:00
abstract::Solid organ transplant recipients (SOTRs) are susceptible to various cutaneous side effects as a consequence of long-term immunosuppressive therapy. Skin cancers and infections are well-studied complications that can cause death and/or allograft rejection. Other cutaneous drug reactions, such as inflammatory manifesta...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2020.101355
更新日期:2021-02-01 00:00:00
abstract:BACKGROUND:Pigs are frequently used as animal models for experiments in the surgical field, including allo- and xeno-transplantation. Regeneration studies, including studies dealing with human- and monkey-induced pluripotent stem cells (iPSC), have gradually progressed, with pigs sometimes being used as the scaffold. H...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2016.12.002
更新日期:2017-02-01 00:00:00
abstract::Previously, we developed a well-tolerated single-day protocol for induction of stable multilineage chimerism and permanent donor-specific tolerance across major histocompatibility complex (MHC) barriers, with preservation of the host's normal immune responses. In our murine model, recipient mice were treated with a si...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(98)80039-7
更新日期:1998-09-01 00:00:00
abstract::We suggest that surveillance for squamous cell cancer might be particularly useful for transplant patients receiving statin therapy. We recommend that development of non melanoma skin cancer should be specified as a secondary endpoint in future large endpoint statin trials, and suggest that in transplant patients the ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2010.06.001
更新日期:2010-08-01 00:00:00
abstract::Alloreactive T-cell responses directed against minor histocompatibility (H) antigens, which arise from diverse genetic disparities between donor and recipient outside the MHC, are an important cause of rejection of MHC-matched grafts. Because clinically significant responses appear to be directed at only a few antigen...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2013.10.005
更新日期:2013-12-01 00:00:00
abstract:BACKGROUND:Our laboratory has demonstrated that xenogeneic porcine thymus tissue grafted in thymectomized (ATX) and T cell-depleted mice induces donor-specific tolerance. Recipient thymectomy is essential for the success of tolerance induction. In contrast, studies in pigs grafted with non-vascularized allogeneic class...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2005.04.004
更新日期:2005-10-01 00:00:00
abstract:BACKGROUND:Peripheral blood CD4+ T cell adenosine triphosphate (ATP) release has been reported to be an adjunct tool to evaluate global cellular immune response in solid-organ transplant recipients. However, the correlation between the ATP level and rejection was controversial. The aim of this prospective clinical stud...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2013.10.008
更新日期:2014-01-01 00:00:00
abstract::Calcineurin inhibitors (CNI) cyclosporine (Csa) and tacrolimus (Tac) are now first intention immunosuppressive drugs in renal transplantation. However, although these treatments are effective for preventing allograft rejection, they are nephrotoxic: they can cause chronic renal dysfunction and degradation of renal gra...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2008.09.002
更新日期:2008-11-01 00:00:00
abstract:OBJECTIVES:To assess the timelines of serum free light chain (sFLC) concentrations and the kappa/lambda light chain (K/L) ratio in heart transplant (HTX) recipients. To analyze the performance of serum protein electrophoresis (SPE), serum immunofixation (sIFE) and sFLC measurements for gammopathy detection following a ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2017.01.003
更新日期:2017-03-01 00:00:00
abstract::Although natural killer cells lyse targets without pre-sensitization, and in an MHC-unrestricted manner, they can also respond to healthy allogeneic cells of different MHC type. Such alloreactivity is a consequence of NK cells using clonally distributed, inhibitory MHC class I receptors to achieve tolerance to healthy...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/j.trim.2006.09.022
更新日期:2006-12-01 00:00:00
abstract::Dendritic cells (DC) are considered to be the major cell type responsible for induction of primary immune responses. While they have been shown to play a critical role in eliciting allosensitization via the direct pathway, there is evidence that maturational and/or activational heterogeneity between DC in different do...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(00)00010-1
更新日期:2000-03-01 00:00:00
abstract::The myeloid-related proteins 8 and 14 exist as a dimeric complex (MRP 8/14) and serve as early and highly specific markers for inflammatory processes, such as allograft rejection and non-viral (bacterial or fungal) infections. An elevated procalcitonin (PCT) concentration in serum also serves as a diagnostic indicator...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2007.10.004
更新日期:2008-02-01 00:00:00
abstract::Data binding the expression of Toll-like 4 receptor (TLR4ex), transplanted kidney function, and the cause of pre-transplant end-stage renal disease are scarcely available. OBJECTIVE:To investigate the relationship between pre-transplant chronic interstitial nephritis (CIN), TLR4ex and transplanted kidney function. M...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2020.101319
更新日期:2020-10-01 00:00:00
abstract::Application of mesenchymal stromal cells (MSCs) has been proposed for solid organ transplantation based on their potent immuno-modulatory effects in vitro and in vivo. We investigated the potential of MSCs to improve acceptance of kidney transplants in an MHC-incompatible rat model including isogeneic kidney transplan...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2013.08.004
更新日期:2013-12-01 00:00:00
abstract::Using specific cell surface receptors lymphocytes continuously sample their environment. Maturation of the immune system and initiation of a specific immune response rely on an array of extracellular cues that elicit complex intracellular biochemical signals. Essential molecules involved in signal transduction from im...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/s0966-3274(02)00009-6
更新日期:2002-05-01 00:00:00
abstract:OBJECTIVE:The immunomodulator, FTY720, lowers the peripheral lymphocyte count (PLC) by inducing migration of circulating lymphocytes to secondary lymphoid organs. We investigated the efficacy of mono- vs. combined-FTY720/CsA therapy on graft survival (GS) and on lowering the PLC in a solid organ and a skin graft model,...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/s0966-3274(01)00031-4
更新日期:2001-02-01 00:00:00
abstract:BACKGROUND:Antibody-mediated rejection (ABMR) is the leading cause of kidney graft loss worldwide. Criteria for acute humoral rejection (currently labeled active humoral rejection) established by the 2007 Banff classification are highly specific but lack sensitivity. Modifications to the Banff classification were intro...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2018.08.008
更新日期:2018-12-01 00:00:00
abstract::The expression of CD30 is restricted to cells of the immune system and strictly regulated under physiological conditions. However, active immune cells express CD30 and soluble CD30 (sCD30) is released. Several investigators reported the relevance for sCD30 as a predictive marker for allograft rejection following organ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2010.07.001
更新日期:2010-08-01 00:00:00
abstract:INTRODUCTION:Glutathione (GSH) is added to University of Wisconsin (UW) organ preservation solution to protect against oxidative stress. This study assesses the effect of GSH-supplementation on endothelial function in tissues subjected to cold ischaemia and compares its effects to a mono-ethyl ester equivalent (GSH-MEE...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2007.06.002
更新日期:2007-11-01 00:00:00
abstract:BACKGROUND:Conditioning chemotherapies for hematopoietic stem cell transplantation (HSCT), especially those that include total body irradiation, can result in serious complications such as graft-versus-host disease (GVHD). Human leukocyte antigen G (HLA-G) is a non-classical class I molecule with multiple immunoregulat...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2018.12.001
更新日期:2019-04-01 00:00:00
abstract::The induction of antigen-specific T cell tolerance and its maintenance in the periphery are critical for the immune system to prevent autoaggressive immune responses. Our current state of knowledge about the immunoregulatory mechanisms responsible for T cell tolerance in the periphery offers new possibilities for immu...
journal_title:Transplant immunology
pub_type: 杂志文章,评审
doi:10.1016/S0966-3274(03)00057-1
更新日期:2003-07-01 00:00:00
abstract:BACKGROUND:Donor leucocytes (DL) play an important role in rat liver transplant tolerance and their postoperative administration can convert rejection to tolerance. They appear to induce early activation, altered patterns of infiltration and death of recipient alloreactive T cells. The ability of immunosuppressive drug...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2004.05.003
更新日期:2004-11-01 00:00:00
abstract:BACKGROUND:The Fischer-to-Lewis (LEW) rat model of kidney transplantation is a widely accepted and well-characterized model of chronic rejection. In contrast to transplantation in a clinical setting, however, the absence of treatment with immunosuppressants and only minor mismatch of major histocompatibility complexes ...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2016.08.002
更新日期:2016-09-01 00:00:00
abstract::Since data on human herpesvirus 8 (HHV-8) infection in Spain is not available, our purpose was to determine the prevalence of HHV-8 infection and the risk of developing Kaposi's sarcoma (KS) among organ transplant recipients in different geographical areas of Spain. The study population consisted of 1019 liver and kid...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2006.09.008
更新日期:2006-12-01 00:00:00
abstract::Cytokines are important factors determining the outcome of transplantation since host ability in cytokine production may be affected by cytokine gene polymorphisms. The aim of the present study was to investigate the effect of IL-17, IL-23R and IL-21 gene polymorphisms in the outcome of kidney transplantation. A total...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2013.09.006
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:Every transplanted organ relies on a reliable and sound vascular system. Therefore, our study focused on the investigation if platelet inhibition alone or combined with mTOR-inhibition has a beneficial effect on the microvascular integrity in allogeneic murine skin grafts. METHODS:Skin transplantation was p...
journal_title:Transplant immunology
pub_type: 杂志文章
doi:10.1016/j.trim.2015.09.005
更新日期:2015-11-01 00:00:00