Chilling Donors Not as Good as Machine Perfusion for Kidney Transplant

A randomized trial found that therapeutic donor hypothermia did not preserve renal function as well as mechanical perfusion of organs during cold storage.

Compared with kidneys pumped with cold non-oxygenated dialysate after removal, kidneys obtained from brain-dead organ donors who underwent mild therapeutic hypothermia were significantly at risk for delayed graft function. higher (adjusted risk ratio [aRR] 1.72, 95% CI 1.35-2.17), according to Klaus Niemann, M.D., Ph.D., University of California, San Francisco, and colleagues.

Kidneys from donors chilled to 34–35°C (93–95°F) prior to explant were defined as requiring initiation of dialysis during the first 7 days post-transplant compared with kidneys. There was a significantly higher risk of delayed graft function. exposed to both hypothermia and mechanical perfusion (aRR 1.57, 95% CI 1.26-1.96).

The combination therapy was no worse for the donor kidney than mechanical perfusion alone, but it was also not superior in reducing delayed graft function (aRR 1.09, 95% CI 0.85-1.40). New England Journal of Medicine.

Overall, delayed graft function occurred most frequently in the hypothermia group (30%), followed by the combination therapy group (22%), and most commonly in the mechanical perfusion alone group (19%). It wasn’t.

One year after transplantation, allograft survival was similar in all three groups as a secondary outcome of the study.

This prospective trial was designed to determine whether hypothermia alone, a non-resource-intensive strategy, is not inferior to machine perfusion. But Niemann’s group pulled the plug early when it turned out to be actually inferior.

“Our findings provide additional evidence that mechanical perfusion prevents delayed graft function compared to static cold storage, even when the donor was receiving hypothermia.” researchers say.

before trial 38% (OR 0.62, 95% CI 0.43-0.92, P.=0.02) the odds of delayed graft function are low when donors receive hypothermia (34-35°C) versus normothermia (36.5-37.5°C). Both groups of explants were followed by a standard period of cold graft storage.

and Editorial companion New trial results, Paulo Martins, MD, PhD, University of Massachusetts, Worcester, and Winfred Williams, MD, Massachusetts General Hospital, Boston, were included in previous trials with donor normothermia before procurement. For cold static storage only.

“The current standard protocols for procurement and preservation are therefore not directly comparable,” they said.

In the new trial, a total of 910 brain-dead donors and 1,820 donated kidneys were randomized from six US-based organ procurement organizations for the current trial. All donors were at least 18 years old, hemodynamically stable, received low-dose vasopressors, and maintained a mean arterial pressure of ≥60 mm Hg. They also corrected coagulopathy and electrolyte abnormalities. Donated kidneys after cardiac death, end-stage renal disease, or a history of dialysis during end-stage hospitalization were excluded.

Of the randomized kidneys, 1,349 were transplanted: 359 in the hypothermia group, 511 in the mechanical perfusion group, and 479 in the combination group.

Hypothermia used a non-invasive external cooling device with perfusion of the right kidney to bring the donor’s body temperature to a target temperature of 34-35°C. Machine perfusion included normothermia followed by ex situ hypothermia of both kidneys, non-oxygenated machine perfusion. Concomitant therapy included donor hypothermia and mechanical perfusion of the left kidney.

Niemann’s group found that 27% of donors assigned to undergo mechanical perfusion actually failed due to “logistical constraints caused by graft problems or the need for immediate long-distance air transportation.” I pointed out that I didn’t receive it. On the other hand, 11% of kidneys assigned to the hypothermic group underwent mechanical perfusion due to logistical constraints at the transplant hospital or the expectation of very long cold ischemia times.

“These issues will have an ongoing impact on trial design, transplant logistics, and outcomes, so future trials should incorporate mechanistic studies and report procurement intervals,” suggested the editors.

The ideal time between brain death and organ acquisition remains unknown, but the editors noted that the trial did not “carefully control” the cold ischemia time between intervention and control groups. pointed out. This is a design limitation.