How to protect organs on transport
The warm donor kidney
Transplant hearts, kidneys, or lungs from brain-dead donors often don’t work as well as organs from living donors. Tina Jager wants to find out why.
Her experiences in Scotland left one hell of an impression. For her research on how to improve transplant kidneys, PhD candidate Tina Jager went to a farm in Edinburgh. She and her Dutch research colleagues, a Scottish surgeon, and his operating team went there to improve the quality of transplant kidneys from brain-dead donors.
Not human kidneys, of course; after all, she went to a farm, not a hospital. ‘We compared the quality of kidneys in brain-dead and living pigs’, says Jager. That meant they had to actually make the pigs brain dead. ‘That was pretty intense’, she admits. ‘But the results were very illuminating.’
It was all for a good cause.
As a student, Jager joined the Prometheus Kidney Team, a team of medical students that collected blood, urine, and small pieces of kidney tissue during kidney transplants. They would use the material in studies on organ donation.
She’s been familiar with donor transplants since the start of her career; life-saving operations that, even when they do go off without a hitch, unfortunately can’t guarantee a functioning organ. Some patients end up back on the waiting list a few years after receiving a new organ.
We think the issues originate with the donor
The Dutch Kidney Foundation says that most transplant kidneys in the world are from brain-dead donors. Only 45 percent of those kidneys are still functioning after ten years. But when it comes to kidneys from living donors – half of all donations in the Netherlands – 65 percent still work after ten years. In short, they work a lot better. Why?
Jager wanted to find a way to improve the performance of kidneys provided by brain-dead donors. To do this, she focused on the immune system, since that is often where the problem lies.
‘People who receive a transplant organ usually have to take medication’, she explains, ‘to ensure their immune system doesn’t attack the new organ. But we think the problems with the immune system start with the donor.’
In some brain-dead donors, the complement system, one of the systems that is supposed to sound the alarm in case of intruders, starts running amok. It goes off too often and the immune system becomes hyperactive, meaning it will attack everything and anything it encounters. This includes organs, which then become damaged even before they can be transplanted.
It’s a tricky problem to solve. The immune system can’t be subdued too much, because then the body can’t protect itself from viruses and bacteria. It’s important to reach and maintain the correct level of immunity. To do that, you have to know how everything works together.
Organs from a single donor often travel to different hospitals all over Europe
‘Because a single donor can help multiple people, organs usually travel all over Europe to different hospitals.’ These kidneys aren’t kept on ice like they used to be; rather, they’re hooked up to a pump, Which supplied the organ with oxygen and nutrients through a cold liquid. The cold means the kidney goes into a kind of hibernation so it doesn’t get damaged as easily.
During their experiments in Scotland, Jager and her colleagues tried to improve the kidneys of brain-dead donors outside the body. These experiments inspired Jager to administer immune suppressants to the kidney outside the body using the pump.
So what if you used a warm liquid for that instead of a cold one? Theoretically, the kidney would function the same as under normal conditions. Doctors can also test the kidneys some more. It also means that any ‘questionable’ kidneys that do well when connected to the pump could still be transplanted.
That’s good news, because in 2019 alone, there were 1,200 people on the waiting list for a kidney transplant. People usually have to wait two or three years before receiving a new organ.
To test the impact of the warm liquid on the immune response, Jager once again used pig kidneys, since they most resemble human kidneys. She got these kidneys from the slaughterhouse, meaning no pigs died for that research.
She hooked the kidneys up to a pump with warm liquid, oxygen, and a drug aimed at suppressing the complement system. ‘We didn’t manage to suppress the immune response entirely, but we did manage to slow it down.
It’s a small drop in a huge ocean
Other than that, Jager focused on experiments using rats and mice. ‘In those animals, you can switch off one of the parts of the complement system at a time. You can then see the effect of that on the entire system.’
She found out, for example, that every organ most likely has its own ‘alarm suppressant’. ‘We saw that some suppressants did work on kidneys, but not on lungs.’ The liver, on the contrary, seems to thrive on an active complement system.
‘A small piece of liver can grow into a fully functioning organ’, she explains. ‘The complement system potentially helps out by engaging active substances to clean up damaged pieces of liver and repairing bits.’
Jager isn’t done yet. The past three years of her research have not led to a ready-made solution to the immune problems. But she’s made important headway, she says. ‘It’s a small drop in a huge ocean.’