Ischaemic Preconditioning in Renal Transplantation

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


Veighey KV et al. British Journal of Anaesthesia, 123 (5): 584e591 2019

Background

Renal transplant is the optimal treatment for end-stage renal failure but during the transplant process the kidney sustains ischaemic damage until perfusion is re-established. This may contribute to the immediate and long-term function of the kidney.

The REPAIR trial investigated whether remote ischaemic preconditioning (RIPC) could improve renal function after living-donor kidney transplantation.

Method  

The study was a multicentre factorial double-blind RCT based across 15 European transplant centres. There were 406 adult donor-recipient pairs. RIPC was performed by inflating a blood pressure cuff on the upper arm to 40mmHg above systolic blood pressure in the intervention group and to 40mmHg in the control group. This was performed for 5 minutes, 4 times. The intervention was undertaken either 24 hours before surgery (late), immediately before surgery (early) or both (dual). This article examined the eGFR results at 2-5 years post-transplant (the 3 month and 1 year data having already been published). 

Results

362 pairs were included in the final analysis.

  • eGFR 5 yr post-transplant
    • Higher in early RIPC group vs control 
    • Adjusted difference in mean eGFR 97% (CI 1.54-7.86, P=0.004)
  • eGRFs early vs late
    • Similar (mean eGFR 1.35 CI -1.83 to 4.53, P=0.41)
    • No evidence of interaction between early and late
  • eGFR late RIPC 
    • Insignificant P values for late group alone (P=0.91)

Discussion

Strengths:

  • Largest study of its kind estimating the effects of RIPC on kidney transplantation
  • Low risk intervention, with a potential to impact a large number of patients.
  • 90% data completion for the 5 year follow up group
  • The use of live-donor transplantation provides a good model for investigating RIPC.

Weaknesses

  • The study is powered to look at the primary end point of iohexol measured GFR at 12 months, rather than the secondary end points of eGFR at 2-5years
  • The data from the dual group was included in the early and late vs sham groups.
  • Confidence intervals in most of the follow up groups are very close to 0, the 5 year follow up group ranges of 0.06-9.80.
  • There is little information regarding anaesthetic technique across the centres, apart from the use of volatiles in all anaesthetics. Anaesthetic technique using volatiles as opposed to TIVA is known to have profound effects on ischaemic preconditioning.

Summary by Dr Lucy Style

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