Randomized clinical trial of daclizumab induction and delayed introduction of tacrolimus for recipients of non-heart-beating kidney transplants

Wilson, CH; Brook, Nicholas R.; Gok, Muhammed A.; Asher, John; Nicholson, Michael L.; Talbot, David

doi:10.1002/bjs.4976

Cited by 23 publications

(13 citation statements)

References 23 publications

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“…58 A prospective randomized trial of 51 recipients of NHB donor kidneys performed in Newcastle upon Tyne and Leicester in the UK showed that induction therapy with the monoclonal antiinterleukin-2-receptor antibody daclizumab can be safely substituted for tacrolimus in the early postoperative period. 59 The duration of DGF did not differ between groups, except for in a subgroup of machine-perfused kidneys in which induction treatment with daclizumab reduced the incidence of DGF. Rates of acute rejection and duration of hospitalization were similar in the two main study groups.…”

Section: Discussionmentioning

confidence: 83%

Non-heartbeating donation of kidneys for transplantation

Kootstra¹,

Heurn²

2007

Nat Rev Nephrol

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There is a persistent shortage of kidneys available for transplantation. In the early 1980s, therefore, we published the concept of non-heartbeating (NHB) donation; that is, procurement of kidneys from donors whose death has been accompanied by irreversible circulatory arrest. NHB donors are generally categorized using four definitions; category III (awaiting cardiac arrest) and category IV (cardiac arrest while braindead)--or 'controlled'--donors are the most suitable for initiating NHB donation programs. Delayed graft function is associated with use of kidneys from such donors, but has no effect on graft survival in the short or long term. Use of kidneys from category I (dead upon arrival at hospital) and category II (unsuccessfully resuscitated), or 'uncontrolled', donors is likewise associated with delayed graft function, but also with an increased risk of primary nonfunction. Viability testing of donated organs from these sources is a prerequisite for transplantation. Machine preservation parameters and enzyme release measurements help to distinguish viable from nonviable kidneys. The proportion of NHB donor kidneys in the total pool of postmortem kidneys differs considerably between countries. In The Netherlands, the proportion is nearly 50%. This figure is markedly higher than that in the US and Canada, where national programs have now been initiated to increase rates of NHB donation. In the future, warm preservation techniques might facilitate better viability testing, thereby increasing NHB donation from category I and II donors and further reducing the shortage of kidneys available for transplantation.

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Section: Discussionmentioning

confidence: 83%

Non-heartbeating donation of kidneys for transplantation

Kootstra¹,

Heurn²

2007

Nat Rev Nephrol

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“…randomized 51 recipients of DCD kidney transplants to induction with daclizumab and daily MMF and compared them with no induction but a standard tacrolimus‐based triple therapy without induction. Although they found a decreased incidence of DGF in daclizumab‐induced recipients with delayed introduction of calcineurin inhibitors, outcome beyond 3 months was not presented [11]. Rivera et al.…”

Section: Discussionmentioning

confidence: 99%

Alemtuzumab induction and triple maintenance immunotherapy in kidney transplantation from donors after cardiac death

Schadde

D’Alessandro

Knechtle

et al. 2008

Transplant International

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Summary We have used alemtuzumab in combination with triple maintenance immunosuppression in renal transplantation from donors after cardiac death between 2002 and 2006. We compared outcomes of induction therapy with alemtuzumab with interleukin‐2 (IL‐2) receptor antagonists (RA) and anti‐lymphocyte antibodies. We used a retrospective sequential study design to examine 170 recipients of kidneys from donor after cardiac death (DCD) for survival, graft survival, time to first rejection, glomerular filtration and complications. Patients were stratified into high‐risk and low‐risk groups based on the following criteria: panel of reactive antibodies >20%, retransplants, Afro‐American race. Induction with alemtuzumab was compared with anti‐thymocyte globulin (ATG) in the high‐risk and with IL‐2RA in the low‐risk group. Patients received triple immunosuppression with steroids, mycophenolate mofetil and calcineurin inhibitors. Patient survival, graft survival, rejection rate and glomerular filtration rate did not significantly differ between patients treated with alemtuzumab versus IL‐2RAs or ATG. There was a trend towards reduced graft‐ and patient survival in the alemtuzumab group. There was an increased incidence of cytomegalovirus (CMV) infections in the alemtuzumab‐induced group and a trend towards increased BK virus and bacterial infections. Induction of DCD kidney transplants with alemtuzumab compared to IL‐2RA and ATG has no significant impact on acute rejection. It appears however that CMV infections are increased in patients induced with alemtuzumab. We therefore conclude that induction with alemtuzumab does not confer any advantage over traditional induction agents.

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“…DCD transplants have been related to a higher incidence of DGF, PNF, and, in some reports, to a higher incidence of AR . In most centers, these results were obtained with CNI‐based immunosuppressive regimens, but with minimization of CNI exposure .…”

Section: Discussionmentioning

confidence: 99%

“…Some authors have proposed minimization of CNI therapy in DCD transplants to avoid DGF, with satisfactory survival and functioning grafts . Other authors have also proposed a CNI‐free treatment and an mTOR‐I‐based therapy in DCD transplants to avoid DGF, with good graft and patient survival .…”

Section: Introductionmentioning

confidence: 99%

An mTOR-inhibitor-based protocol and calcineurin inhibitor (CNI)-free treatment in kidney transplant recipients from donors after cardiac death: good renal function, but high incidence of conversion to CNI

et al. 2016

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SummaryDonor after cardiac death (DCD) grafts have excellent survival despite the high incidence of delayed graft function (DGF). We assessed the feasibility of a mammalian target of rapamycin inhibitor (mTOR-I) protocol in uncontrolled DCD kidney transplantation and compared it with brain-dead donor (DBD) transplantation under calcineurin inhibitor (CNI) treatment.This retrospective study (2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011) included 109 Maastricht category II DCD patients and 218 standard-criteria DBD as controls. Immunosuppression consisted of polyclonal antibody induction, mycophenolate mofetil, prednisone, and mTOR-I (starting on day 6) in the DCD group and tacrolimus in the DBD group. DGF occurred in 72.5% of the DCD group vs. 26.1% of the DBD group (P = 0.001). Patient survival at 1 year was 99.1% vs. 95.9% (P = 0.112), and graft survival was 89% vs. 92.2% (P = 0.253). Patient survival at 5 years was 85.3% vs. 90.1% (P = 0.340) and graft survival was 85.5% vs. 78.8% (P = 0.166). During the first year, 46.8% (n = 51) of DCD patients were converted to CNI therapy. Serum creatinine at 1 year was 1.5(1.26-2) mg/dl vs. 1.4(1.16-1.8) mg/dl (P = 0.078). At 1 year, the acute rejection rate was 7.3% vs. 12.5% (P = 0.766). mTOR-I-based therapy was not associated with inferior graft function or higher rejection rates than standard CNI therapy. DCD kidney transplantation with an mTOR-I-based protocol is feasible but is associated with a high conversion rate to CNI-based therapy.

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Randomized clinical trial of daclizumab induction and delayed introduction of tacrolimus for recipients of non-heart-beating kidney transplants

Abstract: Induction with DZB and delayed introduction of tacrolimus reduced the incidence of DGF in recipients of machine-perfused NHBD kidneys.

Cited by 23 publications

References 23 publications

Non-heartbeating donation of kidneys for transplantation

Non-heartbeating donation of kidneys for transplantation

Alemtuzumab induction and triple maintenance immunotherapy in kidney transplantation from donors after cardiac death

An mTOR-inhibitor-based protocol and calcineurin inhibitor (CNI)-free treatment in kidney transplant recipients from donors after cardiac death: good renal function, but high incidence of conversion to CNI

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