Comparison of four different immunosuppression protocols without long-term steroid therapy in kidney recipients monitored by surveillance biopsy: five-year outcomes.

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 Steroids were withdrawn on post-transplant day 2, and long-term steroid therapy was not used.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 Immunol

journal_title

Transplant immunology

authors

Anil Kumar MS,Irfan Saeed M,Ranganna K,Malat G,Sustento-Reodica N,Kumar AM,Meyers WC

doi

10.1016/j.trim.2008.08.005

subject

Has Abstract

pub_date

2008-11-01 00:00:00

pages

32-42

issue

1-2

eissn

0966-3274

issn

1878-5492

pii

S0966-3274(08)00074-9

journal_volume

20

pub_type

杂志文章,随机对照试验
  • Effect of IL-18 and sIL2R on aGVHD occurrence after hematopoietic stem cell transplantation in some Iranian patients.

    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

    authors: Shaiegan M,Iravani M,Babaee GR,Ghavamzadeh A

    更新日期:2006-01-01 00:00:00

  • Transplantation of adipose tissue protects BB/OK rats from type 1 diabetes development.

    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

    authors: Bahr J,Klöting N,Klöting I,Follak N

    更新日期:2011-05-01 00:00:00

  • Engraftment of human T, B and NK cells in CB.17 SCID/beige mice by transfer of human spleen cells.

    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

    authors: Yacoub-Youssef H,Marcheix B,Calise D,Thiers JC,Therville N,Benoist H,Blaes N,Ségui B,Dambrin C,Thomsen M

    更新日期:2005-12-01 00:00:00

  • Limiting dilution analysis: quantification of IL-2 producing allospecific lymphocytes after renal and cardiac transplantation.

    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

    authors: Cattell EL,Cunningham AC,Bal W,Taylor RM,Dark JH,Kirby JA

    更新日期:1994-12-01 00:00:00

  • Immunosuppressant-induced cutaneous drug reactions in solid organ transplant recipients.

    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

    authors: Miotto IZ,Souza BCE,Tyring SK,de Oliveira WRP

    更新日期:2021-02-01 00:00:00

  • Studies of innate immune systems against human cells.

    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

    authors: Sakai R,Kitano E,Maeda A,Lo PC,Eguchi H,Watanabe M,Nagashima H,Okuyama H,Miyagawa S

    更新日期:2017-02-01 00:00:00

  • An alternative conditioning regimen for induction of specific skin graft tolerance across full major histocompatibility complex barriers.

    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

    authors: de Vries-van der Zwan A,van der Pol MA,de Waal LP,Boog CJ

    更新日期:1998-09-01 00:00:00

  • Why statin therapy may increase the risk for posttransplantation squamous cell carcinoma.

    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

    authors: Mascitelli L,Pezzetta F,Goldstein MR

    更新日期:2010-08-01 00:00:00

  • Deletion of naïve T cells recognizing the minor histocompatibility antigen HY with toxin-coupled peptide-MHC class I tetramers inhibits cognate CTL responses and alters immunodominance.

    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

    authors: Hess SM,Young EF,Miller KR,Vincent BG,Buntzman AS,Collins EJ,Frelinger JA,Hess PR

    更新日期:2013-12-01 00:00:00

  • Host thymectomy and cyclosporine lead to unstable skin graft tolerance after class I mismatched allogeneic neonatal thymic transplantation in mice.

    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

    authors: Rodríguez-Barbosa JI,Haller GW,Zhao G,Sachs DH,Sykes M

    更新日期:2005-10-01 00:00:00

  • Increased intracellular adenosine triphosphate level as an index to predict acute rejection in kidney transplant recipients.

    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

    authors: Wang XZ,Jin ZK,Tian XH,Xue WJ,Tian PX,Ding XM,Zheng J,Li Y,Jing X,Luo ZZ

    更新日期:2014-01-01 00:00:00

  • Prevention of calcineurin inhibitor nephrotoxicity in renal transplantation.

    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

    authors: Jacquet A,Francois H,Frangie C,Ahmad L,Charpentier B,Durrbach A

    更新日期:2008-11-01 00:00:00

  • Free light chain and intact immunoglobulin abnormalities in heart transplant recipients: Two year follow-up timelines and clinical correlations.

    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

    authors: Sečník P Jr,Lavríková P,Hošková L,Malíková P,Jabor A,Franeková J

    更新日期:2017-03-01 00:00:00

  • Do NK-cell receptors and alloreactivity affect solid organ transplantation?

    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

    authors: Vilches C,Parham P

    更新日期:2006-12-01 00:00:00

  • Comparative analysis of dendritic cell density and total number in commonly transplanted organs: morphometric estimation in normal mice.

    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

    authors: Steptoe RJ,Patel RK,Subbotin VM,Thomson AW

    更新日期:2000-03-01 00:00:00

  • Combined use of myeloid-related protein 8/14 and procalcitonin as diagnostic markers for acute allograft rejection in kidney transplantation recipients.

    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

    authors: Jung DY,Park JB,Lee EN,Lee HA,Joh JW,Kwon CH,Ki CS,Lee SY,Kim SJ

    更新日期:2008-02-01 00:00:00

  • Toll-like 4 receptor (TLR4) expression on peripheral blood mononuclear cells in renal transplant recipients with pre-transplant chronic interstitial nephritis indicates patients at risk of graft deterioration.

    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

    authors: Zmonarski SC,Banasik M,Golebiowski T,Madziarska K,Mazanowska O,Myszka M,Zmonarska J,Letachowicz K,Dawiskiba T,Krajewska M

    更新日期:2020-10-01 00:00:00

  • Isogeneic MSC application in a rat model of acute renal allograft rejection modulates immune response but does not prolong allograft survival.

    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

    authors: Koch M,Lehnhardt A,Hu X,Brunswig-Spickenheier B,Stolk M,Bröcker V,Noriega M,Seifert M,Lange C

    更新日期:2013-12-01 00:00:00

  • Signal transduction and co-stimulatory pathways.

    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

    authors: Kiefer F,Vogel WF,Arnold R

    更新日期:2002-05-01 00:00:00

  • Combined FTY720/cyclosporine A treatment promotes graft survival and lowers the peripheral lymphocyte count in DA to lewis heart and skin transplantation models.

    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

    authors: Nikolova Z,Hof A,Baumlin Y,Hof RP

    更新日期:2001-02-01 00:00:00

  • Antibody-mediated rejection in the Banff classifications of 2007 and 2017: A comparison of renal graft loss prediction capability.

    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

    authors: Solar-Cafaggi D,Marino L,Uribe-Uribe N,Morales-Buenrostro LE

    更新日期:2018-12-01 00:00:00

  • A prospective study of serum soluble CD30 in allogeneic hematopoietic stem cell transplantation.

    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

    authors: Hübel K,Cremer B,Heuser E,von Strandmann EP,Hallek M,Hansen HP

    更新日期:2010-08-01 00:00:00

  • Glutathione supplementation to University of Wisconsin solution causes endothelial dysfunction.

    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

    authors: Tambyraja AL,Mitchell R,Driscoll PJ,Deans C,Parks RW,Rahman I,Megson IL

    更新日期:2007-11-01 00:00:00

  • Effects of recombinant thrombomodulin therapy and soluble human leukocyte antigen-G levels during hematopoietic stem cell transplantation.

    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

    authors: Nomura S,Ito T,Katayama Y,Ota S,Hayashi K,Fujita S,Satake A,Ishii K

    更新日期:2019-04-01 00:00:00

  • Immune regulation by regulatory T cells: implications for transplantation.

    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

    authors: Jonuleit H,Adema G,Schmitt E

    更新日期:2003-07-01 00:00:00

  • Combined donor leucocyte administration and immunosuppressive drug treatment for survival of rat heart allografts.

    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

    authors: den Dulk M,Wang C,Li J,Clark DA,Hibberd AD,Terpstra OT,McCaughan GW,Bishop GA

    更新日期:2004-11-01 00:00:00

  • A chronic renal rejection model with a fully MHC-mismatched rat strain combination under immunosuppressive therapy.

    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

    authors: Hanaoka K,Kawato Y,Kubo K,Nakanishi T,Maeda M,Nakamura K,Hirose J,Noto T,Fukahori H,Fujikawa A,Miyoshi S,Takakura S,Morokata T,Higashi Y

    更新日期:2016-09-01 00:00:00

  • Human herpesvirus-8 infection and Kaposi's sarcoma after liver and kidney transplantation in different geographical areas of Spain.

    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

    authors: García-Astudillo LA,Leyva-Cobián F

    更新日期:2006-12-01 00:00:00

  • Combined analysis of cytokine gene polymorphism and the level of expression with allograft function in kidney transplant recipients.

    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

    authors: Karimi MH,Hejr S,Geramizadeh B,Yaghobi R,Sagheb MM,Kamali-Sarvestani E

    更新日期:2014-01-01 00:00:00

  • Microvascular integrity plays an important role for graft survival after experimental skin transplantation.

    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

    authors: Motsch B,Heim C,Koch N,Ramsperger-Gleixner M,Weyand M,Ensminger SM

    更新日期:2015-11-01 00:00:00