Renal protection against ischaemia-reperfusion injury in transplantation

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Scientific Abstract Design: Multicentre double-blind randomised controlled trial Setting: Kidney transplant units in the UK and Holland Target population: Patients undergoing living donor kidney transplantation Intervention being evaluated: Intermittent limb ischaemia to induce remote ischaemic preconditioning prior to kidney transplantation Measurement of outcomes and duration of follow up Primary outcome: glomerular filtration rate (GFR) 12 months after transplantation Secondary outcomes 1.Time for serum creatinine to fall by 50% 2.eGFR 6 months after transplantation 3.Kidney graft cortical tubulointerstitial fibrosis at 6 months (digital analysis of Sirius red staining in biopsy material) 4.RIPC-induced protein expressional changes in kidney tissue 5.Incidence of delayed graft function (serum creatinine levels increase, remain unchanged, or decrease less than 10% per day in three consecutive days in the first week after transplantation) 6.Incidence of acute rejection during the first 12 months after transplantation 7.Long-term outcomes using renal registry data 2-5 years after transplantation (serum creatinine/eGFR, graft survival, patient survival) Duration of follow-up:1 year within the trial, 5 year follow-up using renal registry data Sample size: Randomisation (8:6:6:3 schedule) will be between control (n=135), late RIPC (n=100), dual RIPC (n=100) and recipient-only RIPC (n=50) , recruiting 385 patients in total. For the primary analysis, this gives 80% power to detect a 10% difference in GFR at 12 months between control and late/dual RIPC. This also enables secondary analyses, with 80% power to detect a 12.5% difference in GFR at 12 months, and a 15% difference in the time for creatinine to halve post-transplantation between between late RIPC and dual RIPC. An exploratory comparison will be made between control and recipient-only RIPC; 50 patients in this group gives 80% power to detect a 20% difference in the time for creatinine to halve post-transplantation. Planned analysis: There is no interim analysis; final analysis of primary and all secondary end-points will be at 12 months, with the exception of GFR at 2-5 years Project timetables including recruitment rates: -4 to 0 months: ethics and R+D approval 0 to 3 months: trial set-up at each centre, research nurse recruitment and training, case report form design and preparation 4 to 12 months; recruit the first 150 patients 12 to 24 months; follow up of first 150 patients and recruitment of further 200 patients 24 to 39 months; recruitment of 30 patients, completion of annual follow up 33 to 42 months; data collection, tissue analysis, trial closure and unblinding, and data analysis.