Abstract
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.
Highlights
Renal transplantation is the best treatment for kidney failure, in terms of length and quality of life and cost-effectiveness
We 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
Summary
Research by others working in this area has mostly focussed on how to treat established CR. 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]. There is no direct evidence from the transplant literature to support this intervention, but a similar treatment course is standard therapy in many situations where quick and effective suppression of immune responses is required, for example in acute asthma and in many types of autoimmune diseases. This trial will identify a group of patients at high risk of premature transplant failure.
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