Introduction and Aims: Delayed graft function is a frequent complication following deceased donor renal transplantation and is closely related to ischaemia-reperfusion injury. Experimental and clinical studies have shown protection by remote ischemic conditioning (RIC). We hypothesised that RIC applied to the recipient before kidney graft reperfusion reduces the time to graft recovery.
Methods: This multicentre, randomised, controlled clinical trial included adult recipients of renal transplants from deceased donors at four transplantation centres in Denmark, Sweden and the Netherlands. Participants were randomised 1:1 to RIC or sham-RIC by online block randomisation, stratified by centre, donor type, and within kidney pairs if applicable. RIC consisted of 4x5 min of thigh occlusion by an inflatable tourniquet each followed by 5 min of deflation performed during surgery, prior to graft reperfusion. The tourniquet remained deflated for sham-RIC. Patients and physicians were blinded to the intervention. Primary endpoint was the estimated time to a 50% decrease in baseline plasma creatinine (tCr50) calculated from plasma creatinine measurements 30 days post-transplant or 30 days after the last, post-transplant dialysis. Estimated GFR (eGFR) 21 days post-transplant was calculated using the simplified Modification of Diet in Renal Disease (MDRD) formula without correction for race. Plasma neutrophil gelatinase-associated lipocalin (NGAL) day 0-3 was measured using a particle-enhanced turbidometric immunoassay (NGAL,®BioPorto Diagnostics A/S, Denmark). A mixed regression model with intervention and centre as fixed effects and donor as random effect was used to compare log transformed outcomes between groups.
Results: 225 patients were included, 109 in the RIC and 113 in the sham-RIC group, three were withdrawn during surgery. No significant differences were observed between groups comparing cold ischaemia time, recipient and donor characteristics. No significant differences were observed between RIC and sham-RIC treated patients in the primary outcome of median tCr50 (122h [95%-CI 98-151] vs. 112h [95%-CI 91-139], P=0.58), median eGFR 21 days post-transplant (39 ml/min/1.73m2 [95%-CI 36-43] vs. 39 ml/min/1.73m2 [95%-CI 36-42], P=0.59), or the number of patients receiving dialysis first post-transplant week (36/109 (33%), vs. 38/113 (34%), P=0.92). FIGURE No significant differences in plasma NGAL were found between the groups at the different time points (P>0.34 for all) and in the change over time (P=0.57). Estimated median and 95% confidence intervals are shown.
Conclusions: Recipient RIC immediately before graft reperfusion does not reduce the time to graft recovery in kidney transplantation from deceased donors.
Comments