Early remote ischaemic preconditioning leads to sustained improvement in allograft function after live donor kidney transplantation: long-term outcomes in the REnal Protection Against Ischaemia-Reperfusion in transplantation (REPAIR) randomised trial

Br J Anaesth. 2019 Nov;123(5):584-591. doi: 10.1016/j.bja.2019.07.019. Epub 2019 Sep 11.

Abstract

Background: The REnal Protection Against Ischaemia-Reperfusion in transplantation (REPAIR) RCT examined whether remote ischaemic preconditioning (RIPC) improved renal function after living-donor kidney transplantation. The primary endpoint, glomerular filtration rate (GFR), quantified by iohexol at 12 months, suggested that RIPC may confer longer-term benefit. Here, we present yearly follow-up data of estimated GFR for up to 5 yr after transplantation.

Methods: In this double-blind, factorial RCT, we enrolled 406 adult live donor kidney transplant donor-recipient pairs in 15 European transplant centres. RIPC was performed before induction of anaesthesia. RIPC consisted of four 5 min inflations of a BP cuff on the upper arm to 40 mm Hg above systolic BP separated by 5 min periods of cuff deflation. For sham RIPC, cuff inflation to 40 mm Hg was undertaken. Pairs were randomised to sham RIPC, early RIPC only (immediately pre-surgery), late RIPC only (24 h pre-surgery), or dual RIPC (early and late RIPC). The pre-specified secondary outcome of estimated GFR (eGFR) was calculated from serum creatinine measurements, using the Chronic Kidney Disease Epidemiology Collaboration equation. Predefined safety outcomes were mortality and graft loss.

Results: There was a sustained improvement in eGFR after early RIPC, compared with control from 3 months to 5 yr (adjusted mean difference: 4.71 ml min-1 (1.73 m)-2 [95% confidence interval, CI: 1.54-7.89]; P=0.004). Mortality and graft loss were similar between groups (RIPC: 20/205 [9.8%] vs control 24/201 [11.9%]; hazard ratio: 0.79 [95% CI: 0.43-1.43]).

Conclusions: RIPC safely improves long-term kidney function after living-donor renal transplantation when administered before induction of anaesthesia.

Clinical trial registration: ISRCTN30083294.

Keywords: ischaemia–reperfusion; kidney; organ protection; preconditioning; transplant.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Allografts
  • Double-Blind Method
  • Europe
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate / physiology
  • Humans
  • Ischemic Preconditioning / methods*
  • Kidney / physiology
  • Kidney / surgery
  • Kidney Transplantation*
  • Living Donors
  • Male
  • Middle Aged
  • Reperfusion Injury / prevention & control*
  • Time
  • Treatment Outcome
  • Young Adult