Machine Perfusion: Increasing the Safety of Marginal Organ Transplants

The shortage of donor organs is a major global issue. An aging population, a reluctance towards organ donation, and logistical challenges related to organ shipping play an important role in this setting. Machine perfusion can be a way to expand and preserve the donor pool for eligible transplant recipients.

In this MEDICA-tradefair.com interview, PD Dr. Nathanael Raschzok, MD, talks about the application of machine perfusion, explains the differences between methods, and discusses the organs that could benefit from this technique in the future. He also rates its importance in organ transplantation considering the shortage of donor organs.

Dr. Raschzok, you use machine perfusion to precondition donor organs for transplantation. What does this entail?

Dr. Nathanael Raschzok: Machine perfusion in organ transplantation is not a new technique, especially when it comes to abdominal organ transplantation. The first liver transplantations already tried the process. However, machine perfusion was put on the back burner because it was and still is efficient, cost-effective, and easy to use a cold storage solution in organ preservation.

Nearly fifteen years ago, hypothermic machine perfusion became the international gold standard in kidney transplantation. It means organs are typically connected to the perfusion device at the removal center, flushed with a cold preservative solution, and then delivered to the transplant center. I intentionally said international gold standard because for various reasons, it is not the standard in Germany, though the technique has been checked and validated in studies.

There are many exciting developments as it pertains to kidney research. Our hospital compares cold versus warm perfusion in a prospective randomized clinical trial (NCT04644744). With cold (hypothermic) machine perfusion, the organ is flushed with a cold preservative solution. Warm (normothermic) machine perfusion uses a solution with a different configuration containing a hemoglobin-based oxygen carrier. These are typically red blood cells from donors, allowing the oxygenation of organs. They are metabolically active, if supplied with blood or flushed at 37 °C, the postulation being this improves the post-transplant outcome.

We have also seen a similar trend in liver projects over the last ten years. First, hypothermic machine perfusion with a preservative solution was established. In a next step, hypothermic oxygenated machine perfusion ("HOPE") was introduced in liver transplantation. It was primarily developed and used to prepare so-called marginal donor organs. These are organs from donors with limiting criteria or pre-existing conditions that are expected to deliver poorer transplantation results compared to standard organ procurement. Last but not least, the move from hypothermic towards normothermic machine perfusion was made as this is an international practice that is applied in Germany and in clinical trials at our clinical facility.

How is an organ's quality and function assessed during perfusion?

Raschzok: This statement only pertains to the liver: hypothermic oxygenated machine perfusion (HOPE) is still in the development stage in this aspect. A clinical paper from Zurich described a method to quantify metabolites. In the case of normothermic machine perfusion, clinical parameters are used to assess organ function. If the organs return to normal metabolic conditions and resume function, the perfusate shows a reduction in blood lactate concentration. You can also measure liver enzymes that are released into the bloodstream. The assessment of organ function is not yet a clinical standard but a benefit of normothermic machine perfusion.

The aim of this research is to use machine perfusion as a tool to assess the quality of organs that are currently either transplanted under "considerable concern" or not transplanted at all. This marks a huge improvement over static cold storage where the liver transplant takes place directly after cold preservation. In contrast, normothermic machine perfusion can measure parameters that indicate organ function.

You mentioned the liver and the kidneys. What other organs might be suited for this type of perfusion in the future?

Raschzok: The pancreas is another candidate for abdominal organ transplant. However, machine perfusion in this setting is still in the experimental phase. Some of my international colleagues are researching this area, but it is not yet a clinical standard and is also not yet being tested in clinical trials. Looking beyond abdominal organs, there are already perfusion applications pertaining to the heart and the lungs.

How important is perfusion in organ transplantation?

Raschzok: Available data in literature strongly suggests that hypothermic machine perfusion is safer than static cold storage when it comes to marginal organ transplantation.

We posit that normothermic machine perfusion enables the safe transplant of even more marginal organs by facilitating organ quality assessment. This makes machine perfusion already very important because it can make organ transplantation safer. Another hypothesis is that machine perfusion allows us to increase the number of transplants since many marginal organs that are currently not contenders will hopefully turn out to be viable after the quality assessment.

When can we expect this to become a standard practice in organ transplantation?

Raschzok: That depends on the results of the clinical trials. Once these studies have been completed and the responsible committees approve funding for the cost of machine perfusion in Germany, it can become the clinical standard. We should emphasize that static cold storage of organs prior to transplantation likewise renders excellent results. It is also worth mentioning that perfusion necessitates greater logistics efforts, staff training, and higher expenditures. The issue requires a differentiated approach, but I think machine perfusion as a quality assessment tool for marginal organs can and hopefully will become the clinical standard within the next few years.