Five-Year Study of Tacrolimus as Secondary Intervention Versus Continuation of Cyclosporine in Renal Transplant Patients at Risk for Chronic Renal Allograft Failure

Jevnikar, Anthony M.; Arlen, Dianne; Barrett, Brendan; Boucher, Anne; Cardella, Carl J.; Cockfield, Sandra M.; Rush, David; Paraskevas, Steven; Shapiro, Jamie; Shoker, Ahmed; Yılmaz, Serdar; Zaltzman, Jeffrey S.; Kiberd, Bryce A.

doi:10.1097/tp.0b013e318186dd0c

Cited by 6 publications

(5 citation statements)

References 33 publications

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“…Tacrolimus has been identified as a clinically and pharmacoeconomically superior calcineurin inhibitor thus a majority of new transplant recipients should receive tacrolimus [41]. Nevertheless there are no data to suggest that switching from cyclosporin to tacrolimus after stabilization has benefits on long-term outcomes so patients already stabilized on cyclosporin generally remain on it [42][43][44]. This is consistent with utilization patterns seen in this study, with cyclosporin utilization decreasing gradually over time, not dropping off completely.…”

Section: Discussionsupporting

confidence: 78%

Multinational Evaluation of Mycophenolic Acid, Tacrolimus, Cyclosporin, Sirolimus, and Everolimus Utilization

2016

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Section: Discussionsupporting

confidence: 78%

Multinational Evaluation of Mycophenolic Acid, Tacrolimus, Cyclosporin, Sirolimus, and Everolimus Utilization

2016

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“…Finally, some studies have shown that conversion from ciclosporin to tac is beneficial for patients with deteriorating graft function [39], and that introduction of MMF has a similar effect [40]. Although other studies have reported contradictory results [41], much of this literature is difficult to interpret because many studies do not distinguish between CR and other causes of chronic graft dysfunction [42]. …”

Section: Discussionmentioning

confidence: 99%

Can a combined screening/treatment programme prevent premature failure of renal transplants due to chronic rejection in patients with HLA antibodies: study protocol for the multicentre randomised controlled OuTSMART trial

Dorling

Rebollo‐Mesa

Hilton

et al. 2014

Trials

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BackgroundRenal transplantation is the best treatment for kidney failure, in terms of length and quality of life and cost-effectiveness. However, most transplants fail after 10 to 12 years, consigning patients back onto dialysis. Damage by the immune system accounts for approximately 50% of failing transplants and it is possible to identify patients at risk by screening for the presence of antibodies against human leukocyte antigens. However, it is not clear how best to treat patients with antibodies. This trial will test a combined screening and treatment protocol in renal transplant recipients.Methods/DesignRecipients >1 year post-transplantation, aged 18 to 70 with an estimated glomerular filtration rate >30 mL/min will be randomly allocated to blinded or unblinded screening arms, before being screened for the presence of antibodies. In the unblinded arm, test results will be revealed. Those with antibodies will have biomarker-led care, consisting of a change in their anti-rejection drugs to prednisone, tacrolimus and mycophenolate mofetil. In the blinded arm, screening results will be double blinded and all recruits will remain on current therapy (standard care). In both arms, those without antibodies will be retested every 8 months for 3 years. The primary outcome is the 3-year kidney failure rate for the antibody-positive recruits, as measured by initiation of long-term dialysis or re-transplantation, predicted to be approximately 20% in the standard care group but <10% in biomarker-led care. The secondary outcomes include the rate of transplant dysfunction, incidence of infection, cancer and diabetes mellitus, an analysis of adherence with medication and a health economic analysis of the combined screening and treatment protocol. Blood samples will be collected and stored every 4 months and will form the basis of separately funded studies to identify new biomarkers associated with the outcomes.DiscussionWe have evidence that the biomarker-led care regime will be effective at preventing graft dysfunction and expect this to feed through to graft survival. This trial will confirm the benefit of routine screening and lead to a greater understanding of how to keep kidney transplants working longer.Trial registrationCurrent Controlled Trials ISRCTN46157828.

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“…Twoyear follow-up results were improvement in creatinine and lipid profile, with significantly fewer cardiovascular events without differences in acute rejection or new-onset hyperglycemia incidences after conversion [52]. However, results from the same study after 5 years of follow-up do not demonstrated impact on patient or graft survival [53]; these follow-up findings are almost shared by other multicenter randomized trials with similar design [65][66][67][68]. Some critics in these studies remained over the fact that some irreversible fibrosis at enrollment time limited the possibility of showing a less toxic profile of tacrolimus; other explanations include a higher exposure to mycophenolic acid in tacrolimus group (an interaction between cyclosporine and mycophenolic acid reduces plasma levels of the latter) and cyclosporine through levels relatively higher in patients with dysfunction late after transplantation [62,[69][70][71][72][73].…”

Section: Switching To Another Calcineurin Inhibitormentioning

confidence: 79%

Cyclosporine Therapy for Kidney Transplant: What is New for an Old-Fashioned Therapy?

Pedroso¹,

Citterio²

2015

J Clin Toxicol

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Calcineurin inhibitors have been the mainstay of immunosuppression for the last decades and nowadays still remain as relevant drugs in the setting of solid organ transplantation. Nevertheless, the balance between excess of immunosuppression with cyclosporine (leading to increased risk of metabolic complications, nephrotoxicity or cancer), or its insufficiency (with augmented risk of rejection), is even so a challenge in the clinical practice. The aim of this paper is to review the pharmacokinetic and pharmacodynamic evolution of this landmark drug. We also discuss what could we expect on this CNI drug in this decade.

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Five-Year Study of Tacrolimus as Secondary Intervention Versus Continuation of Cyclosporine in Renal Transplant Patients at Risk for Chronic Renal Allograft Failure

Abstract: In this study, patients with chronic allograft damage converted from cyclosporine to tacrolimus demonstrated no apparent benefit.

Cited by 6 publications

References 33 publications

Multinational Evaluation of Mycophenolic Acid, Tacrolimus, Cyclosporin, Sirolimus, and Everolimus Utilization

Multinational Evaluation of Mycophenolic Acid, Tacrolimus, Cyclosporin, Sirolimus, and Everolimus Utilization

Can a combined screening/treatment programme prevent premature failure of renal transplants due to chronic rejection in patients with HLA antibodies: study protocol for the multicentre randomised controlled OuTSMART trial

Cyclosporine Therapy for Kidney Transplant: What is New for an Old-Fashioned Therapy?

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