Nationwide study: effectiveness of aNRP for donor livers

A nationwide randomized study is being conducted in 3 Dutch liver centers. Researchers are investigating whether abdominal normothermic regional perfusion (aNRP) keeps abdominal organs from deceased donors better suited for transplantation than the usual cold perfusion outside the body.

Effect of aNRP on DCD donor livers

An increasing proportion of organ donors have died after circulatory arrest. These are the so-called DCD donors (Donation after Circulatory Death). DCD donor organs suffer from oxygen deprivation because oxygen-rich blood no longer flows to them. These donor organs are therefore often rejected.

‘Until now, this problem has mainly affected donor livers, but we may be able to change this with aNRP,’ says transplant surgeon Volkert Huurman of the LUMC. Together with fellow transplant surgeons Jeroen de Jonge (Erasmus MC) and Vincent de Meijer (UMCG), he is investigating the possibilities of aNRP. This also includes looking at cost-effectiveness and efficiency in the chain.

Opportunities for the donor organ shortage

‘This technique offers an opportunity to reduce the growing shortage of donor organs. Organs that previously fell outside the acceptance criteria and were rejected can now be assessed for actual function. Sometimes they then become eligible for transplantation after all.’

What does the standard procedure look like?

In a standard procedure for DCD donors, the organs are retrieved, flushed outside the body with cold fluid, and then stored in a cooler on ice. This is called cold storage. In the Netherlands, all retrieved DCD donor livers are connected to a perfusion machine upon arrival at the receiving hospital, which pumps storage fluid at 10-12°C with added oxygen through the liver. This is called cold perfusion.

Possible advantages of aNRP

Compared to the standard procedure, cold storage followed by cold perfusion, aNRP potentially has a number of advantages:

• By providing the organs with oxygen-rich blood (almost) immediately, any damage is stopped quickly after it occurs.
• aNRP makes it possible to take blood samples during pumping and determine the extent of organ damage, especially of the liver. This can reduce the risk of a non-functioning donor organ for the recipient.
• The retrieval procedure does not have to be performed under as much time pressure. The surgeon can then operate more carefully, potentially resulting in less injury to the donor organs.
• aNRP simultaneously treats the liver, both kidneys, and the pancreas. A-NRP likely offers the most added value for the liver, but also appears safe for donor kidneys and the pancreas.

Furthermore, the researchers expect that aNRP will lead to fewer complications after liver transplantation and lower costs compared to the current standard treatment.

Potential disadvantages of aNRP

De Jonge: 'No, not really. For surviving relatives, the only potential disadvantage is that the donor's body remains in the operating room slightly longer, as the procedure takes about an hour and a half longer. When the body is returned to the relatives, it is not visible to them that a different technique was used.'

The researchers emphasize that their study concerns only abdominal NRP and therefore not thoraco-abdominal NRP. De Jonge: 'This means that oxygenated blood is only circulated in the abdominal cavity and not higher up in the body.'

Looking across the border

aNRP is already being used successfully in several European countries. For example, it is used as standard practice for DCD donations in France, Italy, Spain, and Norway. Based on positive experiences in other countries, the Ministry of Health, Welfare and Sport (VWS) made a subsidy available in 2018 to introduce A-NRP in the Netherlands and to investigate whether the method can lead to additional donor organs.

Pilot with VWS subsidy

'With that subsidy from VWS, we carried out a pilot project in which we applied A-NRP to DCD donors from whom, normally, only the kidneys could be transplanted due to their advanced age. At that time, we didn't really dare to transplant their livers because we didn't know if the quality was sufficient,' says Huurman.

'Now that this study has been successfully completed, we will compare the results of A-NRP with those of the standard procedure using cold perfusion in the receiving center in a follow-up study.'

Internationally unique study

According to Huurman, it is internationally unique that this comparison can be made. 'In most countries, a choice has already been made for or against aNRP, and in some cases, it is even legally established which technique must be used. In the Netherlands, we have the expertise for both techniques, and both are reimbursed. This allows us to be the first to compare these techniques in a randomized study, so that we can soon substantiate the potential benefits of A-NRP. We really owe that to the innovation-oriented government here.'

Also beneficial for kidney transplantation?

With the study, the researchers also want to find out whether the current method of kidney preservation is still the right one. After removal, donor kidneys are standardly connected to a machine that pumps cold fluid through them until the kidney is implanted in the recipient.

'Some previous studies showed that aNRP was also beneficial for outcomes after kidney transplantation. That is why we want to know whether cold kidney perfusion can be omitted after aNRP. We are now in a position to find that out,' explains Huurman. 'Because you have two kidneys, after aNRP has been applied, you can connect one kidney to a pump and not the other, and see if that has an impact on the outcomes.'

Smooth collaboration

Every 3 weeks, all those involved meet to discuss the progress of the project. 'The NTS is an important party in this. It is not only a full-fledged discussion partner but also has a coordinating role. The interplay between the NTS, the National Health Care Institute, VWS, and our substantive input allows us to do this now. That is very beautiful,' says De Meijer.

Goal: more transplantations

De Jonge: 'We hope to achieve that, ultimately, more transplantations can be performed with responsible use of resources. If everything goes as planned, we can answer the question of what the best technique for this is by the end of 2029.'