Normothermic machine perfusion versus static cold storage in donation after circulatory death kidney transplantation: a randomized controlled trial

Abstract

Kidney transplantation is the optimal treatment for end-stage renal disease, but it is still severely limited by a lack of suitable organ donors. Kidneys from donation after circulatory death (DCD) donors have been used to increase transplant rates, but these organs are susceptible to cold ischemic injury in the storage period before transplantation, the clinical consequence of which is high rates of delayed graft function (DGF). Normothermic machine perfusion (NMP) is an emerging technique that circulates a warmed, oxygenated red-cell-based perfusate through the kidney to maintain near-physiological conditions. We conducted a randomized controlled trial to compare the outcome of DCD kidney transplants after conventional static cold storage (SCS) alone or SCS plus 1-h NMP. A total of 338 kidneys were randomly allocated to SCS (n = 168) or NMP (n = 170), and 277 kidneys were included in the final intention-to-treat analysis. The primary endpoint was DGF, defined as the requirement for dialysis in the first 7 d after transplant. The rate of DGF was 82 of 135 (60.7%) in NMP kidneys versus 83 of 142 (58.5%) in SCS kidneys (adjusted odds ratio (95% confidence interval) 1.13 (0.69–1.84); P = 0.624). NMP was not associated with any increase in transplant thrombosis, infectious complications or any other adverse events. A 1-h period of NMP at the end of SCS did not reduce the rate of DGF in DCD kidneys. NMP was demonstrated to be feasible, safe and suitable for clinical application. Trial registration number: ISRCTN15821205.

Enzymatic conversion of human blood group A kidneys to universal blood group O

“…It is of particular interest that we have shown the Fp GalNAc DeAc and Fp GalNase can function effectively during HMP. While NMP has been shown to be safe and feasible for human kidney transplantation in a recent randomised control trial 13 , clinical implementation of organ perfusion as standard of care has only been achieved for hypothermic machine perfusion. Indeed, HMP has been shown to reduce delayed graft function and primary non-function compared to static cold storage in a recent meta-analysis 14 .…”

Acellular Perfusate is an Adequate Alternative to Packed Red Blood Cells During Normothermic Human Kidney Perfusion

“… 10 , 11 In DCD kidney, transplant of a 1-h period of NMP at the end of SCS did not reduce the rate of DGF compared to SCS alone. 32 The efficacy of NMP for a longer period or continuous (initiated at the donor hospital) NMP needs to be tested for future trials.…”

A Novel Hypobaric Perfusion Method to Remove Microthrombi in Kidney Grafts with Prolonged Circulatory Arrest: A Pilot Study on a Porcine Model

“… 4 Various innovations have targeted the maintenance or improvement of graft function, including a variety of organ preservation solutions (eg, University of Wisconsin solution, Euro-Collins solution, Histidine-Tryptophan-Ketoglutarate solution), 11 - 13 perfusion techniques (eg, ex situ machine perfusion, regional perfusion), 6 , 19 hydrodynamic parameters (eg, continuous, pulsatile), 20 , 21 and perfusion temperatures (eg, hypothermic, normothermic). 22 , 23 As the superiority of hypothermic machine perfusion over conventional static cold storage has been demonstrated, this technique has been widely used in clinical practice. 6 However, few studies have investigated the effects of using pharmacological agents and enzymes, such as kinases, 14 to flush intraorgan microthrombi, and no studies have focused on investigating the environmental pressure under which perfusion is performed.…”