Title: Renal protection against ischaemia-reperfusion injury in transplantation
Funder: Department of Health (England)

Abstract: Design: Multicentre double-blind randomised controlled trialSetting: Kidney transplant units in the UK and HollandTarget population: Patients undergoing living donor kidney transplantationIntervention being evaluated: Intermittent limb ischaemia to induce remote ischaemic preconditioning prior to kidney transplantationMeasurement of outcomes and duration of follow upPrimary outcome: glomerular filtration rate (GFR) 12 months after transplantationSecondary outcomes1.Time for serum creatinine to fall by 50%2.eGFR 6 months after transplantation3.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 tissue5.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 transplantation7.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 dataSample 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 yearsProject timetables including recruitment rates: -4 to 0 months: ethics and R+D approval0 to 3 months: trial set-up at each centre research nurse recruitment and training case report form design and preparation4 to 12 months; recruit the first 150 patients12 to 24 months; follow up of first 150 patients and recruitment of further 200 patients24 to 39 months; recruitment of 30 patients completion of annual follow up33 to 42 months; data collection tissue analysis trial closure and unblinding and data analysis Expertise Clinical trial management: Rosemary Knight and Tim Clayton. Clinical trial design: Rosemary Knight Tim Clayton John Deanfield Chris Watson Raymond MacAllisterClinical and research expertise in kidney disease and transplantation: Chris Watson Hans DeFijter Mark Harber Mike Nicholson Paul Lear Andrew Ready and Geoff Koffman are the clinical leads for renal transplantation in their respective units. Basic and clinical studies in ischaemia-reperfusion injury and ischaemic preconditioning: Raymond MacAllister Stavros Loukogeorgakis Mike Nicholson and John Deanfield Immunoblotting: Raymond MacAllisterBiochemical analyses: Neil DaltonData analysis and statistics: Rosemary Knight and Tim Clayton


Research activity codes: 6.7 PHYSICAL
Health categories: RENAL AND UROGENITAL