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.
BACKGROUND
Renal 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
Recipients>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.


CONCLUSIONS
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.


BACKGROUND
Current Controlled Trials ISRCTN46157828.
MRC Centre for Transplantation, King's College London, Guy's Hospital, Great Maze Pond, London SE1 9RT, UK. anthony.dorling@kcl.ac.uk.
Anthony
A
Dorling
Irene
I
Rebollo-Mesa
Rachel
R
Hilton
Janet L
JL
Peacock
Robert
R
Vaughan
Leanne
L
Gardner
Guilherme
G
Danzi
Richard
R
Baker
Brendan
B
Clark
Raj C
RC
Thuraisingham
Matthew
M
Buckland
Michael
M
Picton
Susan
S
Martin
Richard
R
Borrows
David
D
Briggs
Robert
R
Horne
Paul
P
McCrone
Joanna
J
Kelly
Caroline
C
Murphy
D015415:Biomarkers / Q000097:blood; D002908:Chronic Disease; D002985:Clinical Protocols; D003362:Cost-Benefit Analysis; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D006084:Graft Rejection / Q000191:economics / Q000276:immunology / Q000517:prevention & control*; D006085:Graft Survival / Q000187:drug effects*; D006680:HLA Antigens / Q000276:immunology*; D017048:Health Care Costs; D006648:Histocompatibility; D006650:Histocompatibility Testing / Q000191:economics; D006801:Humans; D007166:Immunosuppressive Agents / Q000191:economics / Q000627:therapeutic use*; D007518:Isoantibodies / Q000097:blood*; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000191:economics; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome; D006113:United Kingdom
D015415:Biomarkers; D006680:HLA Antigens; D007166:Immunosuppressive Agents; D007518:Isoantibodies