Protocol of a randomised controlled, open-label trial of ex vivo normothermic perfusion versus static cold storage in donation after circulatory death renal transplantation

Abstract

IntroductionEx vivo normothermic perfusion (EVNP) is a novel technique that reconditions the kidney and restores renal function prior to transplantation. Phase I data from a series of EVNP in extended criteria donor kidneys have established the safety and feasibility of the technique in clinical practice.Methods and analysisThis is a UK-based phase II multicentre randomised controlled trial to assess the efficacy of EVNP compared with the conventional static cold storage technique in donation after circulatory death (DCD) kidney transplantation. 400 patients receiving a kidney from a DCD donor (categories III and IV, controlled) will be recruited into the study. On arrival at the transplant centre, kidneys will be randomised to receive either EVNP (n=200) or remain in static cold storage (n=200). Kidneys undergoing EVNP will be perfused with an oxygenated packed red cell solution at near body temperature for 60 min prior to transplantation. The primary outcome measure will be determined by rates of delayed graft function (DGF) defined as the need for dialysis in the first week post-transplant. Secondary outcome measures include incidences of primary non-function, the duration of DGF, functional DGF defined as <10% fall in serum creatinine for 3 consecutive days in the first week post-transplant, creatinine reduction ratio days 2 and 5, length of hospital stay, rates of biopsy-proven acute rejection, serum creatinine and estimated glomerular filtration rate at 1, 3, 6 and 12 months post-transplant and patient and allograft survival. The EVNP assessment score will be recorded and the level of fibrosis and inflammation will also be measured using tissue, blood and urine samples. Ethics and dissemination. The study has been approved by the National Health Service (NHS) Health Research Authority Research Ethics Committee. The results are expected to be published in 2020.Trial registration numberISRCTN15821205; Pre-results.

The future of organ perfusion and re‐conditioning

“…Their first clinical trial resulted in a significantly lower DGF rate in normothermically preserved kidneys compared with SCS allografts . They are currently leading a large multi‐centre trial in the United Kingdom to formally investigate the impact of normothermic perfusion on delayed graft function in a trial of DCD kidneys . The decision to transplant an NMP‐kidney is based upon a scoring system developed by Hosgood and Nicholson .…”

The effect on early renal function of various dynamic preservation strategies in a preclinical pig ischemia–reperfusion autotransplant model

“…In 2013, the first clinical study, applying end-ischemic NP after SCS (using kidney grafts originated from ECD) demonstrated a reduction of the DGF rate in favor of the NP group (5.6% vs 36.2%, P = .014). 29 Kaths et al demonstrates that intermediate (8 hours) or prolonged (16 hours) NP following SCS is superior to brief preimplantation NP in a pig kidney transplant model. It could be speculated that the kidneys used in the clinical trial were more damaged organs and therefore may benefit more from the normothermic reconditioning than the kidneys used in our model, which originated from healthy pigs with 30 minutes of warm ischemia by vascular clamping.…”

Dissemination of a novel organ perfusion technique: ex vivo normothermic perfusion of deceased donor kidneys

“…After 5 discarded kidney perfusions at each center, SH discussed any learning points with the EVNP lead from each center (CW and CC) before agreeing that clinical EVNP programs could start. These programs were in place before a randomized controlled trial of EVNP was initiated …”

“…Warm organ perfusion technologies such as ex vivo normothermic perfusion (EVNP) may be able to successfully address some of these concerns. EVNP is a technique using pediatric cardiopulmonary bypass technology enabling the perfusion of an organ with a warm, oxygenated, erythrocyte‐based solution prior to transplantation . Studies suggest that EVNP reduces DGF in extended criteria donor kidneys when compared to historical controls preserved using cold storage alone .…”