Scientists have developed a way to keep donor kidneys functioning outside the human body for several days. The breakthrough could make thousands of organs that are currently discarded suitable for transplantation – and save people who might otherwise die while waiting.
Across the world, tens of thousands of people are waiting for a kidney transplant – and every day, some die before their turn comes. Once the kidneys fail and dialysis becomes necessary, life expectancy falls to just six and a half years.
There are many obstacles: first, finding a compatible donor is difficult. Second, many kidneys from deceased donors are too damaged to be used. And even when everything else succeeds, time is critical: a kidney can normally function for only about 12 hours outside the human body.
As a result, about one quarter of all donated kidneys are never transplanted – and many of the transplanted ones do not function optimally. Now researchers have developed a method that can keep kidneys functioning for days instead of hours, giving doctors the chance to treat and restore them before transplantation.
“The problem is that people who need a new kidney wait far too long,” says Jan Czogalla, Senior Physician and Nephrologist at the University Medical Center Hamburg-Eppendorf in Germany, a scientist behind the new technique. “In Germany, the average waiting time is 11 years, and the life expectancy for people on dialysis is six and a half years – the numbers simply do not add up. We need new methods to bring these two figures together.”
The research has been published in JCI Insight.
When a machine keeps organs going
Jan Czogalla and colleagues have been working to refine normothermic machine perfusion – a sophisticated way of preserving organs before transplantation.
Instead of cooling the kidney on ice, which nearly halts its metabolism, the kidney is kept at normal body temperature and continuously supplied with oxygen-rich blood or a nutrient-filled fluid. In essence, the kidney is connected to an artificial human body that delivers oxygen and energy so it can keep “breathing” and functioning until it is transplanted.
This approach is already being used successfully for livers, extending function outside the human body from about 12 hours to as long as five days – opening new possibilities for transplantation.
“This means that doctors have much more time to examine the liver and even treat it before transplantation,” explains Jan Czogalla. “For instance, a liver that contains too much fat can be improved during storage by using normothermic machine perfusion. Unfortunately, the current methods of normothermic machine perfusion do not work well for kidneys and have not produced convincing results so far.”
The reason lies in biology. Kidney tissue is far more sensitive to changes in blood pressure and oxygen levels than liver tissue, because the kidney must both filter fluids and maintain complex metabolism across millions of microscopic tubes – the nephrons – that purify the blood.
An energy cocktail that resuscitates the kidneys
To determine what a kidney truly needs to keep functioning outside the human body, the researchers carried out a long series of experiments to analyse its metabolism in detail – from its ideal blood pressure to the precise mix of molecules required to keep its cells functioning.
They discovered that some kidney cells work at an astonishing pace, consuming vast amounts of energy. These cells rely on small molecules – metabolites – that serve as both building blocks and fuel. Without them, the cells quickly run out of energy and die soon after the kidney is removed from the human body.
The researchers then asked a simple question: could normothermic machine perfusion be improved by adding these missing metabolites to the perfusion fluid?
At first, none of the metabolites made a difference on their own. But when they were combined – and at higher concentrations – everything changed. The kidneys suddenly began to recover some of their natural energy production, and their filtration function improved markedly.
Next step: human kidneys
Finally, the researchers tested their new method on kidneys from mice and pigs and several human kidneys that had already been deemed unsuitable for transplantation. This enabled them to study the effects safely and ethically while closely measuring how well the kidneys maintained essential functions such as filtration rate and oxygen consumption.
“We found that kidneys perform much better when they are supplied with a solution containing these missing metabolites,” says Jan Czogalla. “They actually regain part of their normal energy production and filtration capacity.”
In the laboratory, the difference was striking: the cells survived longer, and the kidneys functioned as if they were still inside a living human body. “Our next step will be to test the approach on a larger number of human kidneys to determine whether we can extend their survival time before transplantation,” explains Czogalla.
Before that can happen, however, the researchers must obtain regulatory approval from European health authorities for using the added metabolites. “We hope to extend kidney survival outside the human body to as long as five days while also treating the kidneys,” says Czogalla. “This would mean that many more people could receive a kidney that would save their lives.”
