06 September 2013 20:02
“Hundreds of lives a year will be saved if the NHS embraces a transplant revolution involving patients receiving donated kidneys that were previously rejected as inadequate,” The Guardian reported. It said that a new study has given kidneys from people who have died from major heart failure following severe brain injury a “clean bill of health for donation”.
This research found that in patients undergoing their first kidney transplant, there was no difference five years later between kidneys from donors who were brain dead but whose hearts were still beating and those who had a controlled cardiac death (when people have irreversible brain injury and their heart has stopped after life support is switched off). It is important to highlight that this excludes donors who have died on arrival at hospital or who have not responded to resuscitation attempts following a heart attack, for example.
The results of this large, well-conducted study has found that, for first-time recipients, transplants using kidneys taken from controlled-cardiac-death donors have equivalent success rates to those using kidneys from brain-dead donors. Its findings have important implications for future policy on kidney transplants, as until now kidneys from cardiac-death donors were believed to have less chance of success compared to brain-death donors.
WHERE DID THE STORY COME FROM? The study was carried out by researchers from the School of Clinical Medicine, the University of Cambridge, the Cambridge National Institute for Health Research Biomedical Research Centre, the NHS Blood and Transplant, Bristol, and the Nuffield Department of Surgery, University of Oxford.
It was funded by the NHS Blood and Transplant and Cambridge NIHR Biomedical Research Centre. The study was published in the peer-reviewed medical journal, The Lancet.
The study was reported accurately by both the BBC and The Guardian, which both looked at the study’s implications for the future allocation of kidneys for transplant. However, neither news source makes it clear that cardiac death in this instance is restricted to controlled cardiac death where life support has been withdrawn, and does not include the many cardiac deaths that occur in the emergency situation.
WHAT KIND OF RESEARCH WAS THIS? The researchers say that the present demand for kidney transplants far exceeds the supply of donors. This shortfall is becoming more severe as the number of donors fails to keep pace with the growing numbers of patients listed for transplantation.
Most of the kidneys from deceased donors (as opposed to living volunteer donors) are from donors with brain stem death but whose hearts are still beating, usually after a traffic accident or other accident. Problematically, the number of brain-death donors is declining in the UK, thanks in part to a reduction in deaths after accidents.
By contrast, the use of kidneys from non-heart beating donors (cardiac-death donors) has risen steeply. Most of these donors are what doctors call “controlled cardiac-death donors”. These patients have usually suffered irreversible brain injury and died from heart failure after the withdrawal of life support. They do not fulfil the criteria for brain-stem death and death is certified as cessation of cardiopulmonary function.
Although brain stem death and cardiac death both damage the donor kidney, the level of damage differs between the two. There have been concerns that kidneys from cardiac-death donors could be inferior to those from brain-dead donors due to the period of “warm ischaemia” that occurs. This is where the blood supply to the kidney is cut off, between the time the heart stops and cold preservation solution is added. Concerns have also been raised about the long-term outcomes of such transplants, and uncertainty about the factors that might affect their success.
This large cohort study compared the outcomes of kidney transplants from controlled cardiac death donors with the outcomes of kidney transplants from brain death donors. It also investigated what might affect the success of these transplants.
WHAT DID THE RESEARCH INVOLVE? The researchers used data from the UK transplant registry to select a cohort of deceased kidney donors and their corresponding transplant recipients, for transplants carried out between 2000 and 2007. To be included, recipients had to be 18 or over and to have had a transplant from a controlled cardiac death donor (defined as donors awaiting cardiac arrest after withdrawal of life support). Patients who had had “uncontrolled cardiac death” (who were dead on arrival at hospital or where resuscitation has been attempted without success) were excluded. All kidney transplants from brain-death donors were used as a comparison.
The researchers looked at various outcomes, including the time from the operation to “graft failure”, defined as removal of the transplanted kidney, return to kidney dialysis or death of the patient. They also looked at long-term kidney function as measured by the ability of the new kidney to filter blood (the estimated glomerular filtration rate, or eGFR).
Other outcomes were also examined, including acute rejection (when treatment for rejection is needed within the first three months), the length of time between the donor’s heart stopping and the kidney being chilled in a special solution (defined as warm ischaemic time) and the length of time the kidneys were chilled for (defined as cold ischaemic time).
They also considered how well the donor kidney had been matched to the recipient in terms of its HLA match. Human Leukocyte Antigens are proteins on the surface of body tissues; when the HLA on the new kidney cells matches that of the recipient the kidney is less likely to be rejected.
The researchers performed a detailed statistical analysis to look at how the two different groups compared in terms of transplant success. They also analysed the factors associated with graft survival and long-term functioning. They adjusted their analysis for other factors that might have affected transplant success, such as age and smoking habits.
WHAT WERE THE BASIC RESULTS? During the eight-year study period, 9,134 kidney transplants were carried out in 23 centres in the UK. Of these, 8,289 kidneys were donated after brain death (6,759 of which were transplanted into first-time recipients) and 845 after controlled cardiac death (of which 739 were transplanted into first-time recipients).
The researchers found that in the first-time recipients in these two groups, there was no difference in:
the success of the kidney transplant (called graft survival) up to five years later (HR 1.01, 95% CI 0.83 to 1.19) the ability of the kidneys to function (as measured by the eGFR) in the one-to-five years after transplantation They also found that for the recipients of kidneys from cardiac-death donors, certain factors were associated with lower success rates. These were the increasing age of both donor and recipient, repeat transplantation and a cold ischaemic time of more than 12 hours. Delayed graft function, warm ischaemic time and poor HLA match had no significant effect on outcomes.
However, among recipients who had undergone a previous kidney transplant, success among those with kidneys from cardiac death donors was lower than those with kidneys from brain-dead donors.
HOW DID THE RESEARCHERS INTERPRET THE RESULTS? The researchers point out that for patients having their first kidney transplant, kidneys from controlled cardiac-death donors had “excellent results” that had equivalent outcomes to those from kidneys from brain-death donors with heartbeats at up to five years. For first-time recipients, kidneys from controlled cardiac-death donors should be regarded as equivalent to kidneys from brain-dead donors, they say.
They also stress that the factors they found to be associated with worse or better outcomes in the former group, such as age, could be used to improve organ allocation.
CONCLUSION This well-designed study was rigorously carried out and its findings have important implications for the future of kidney transplant service and the way kidneys are allocated. The researchers note, however, that:
Although warm ischaemic time was not associated with an adverse outcome, this finding should be treated with caution because of difficulties in ensuring accurate measurements. Information about immunosuppressive drugs (to prevent graft rejection) was not available so it is unclear if there are any potential differences in regimens or outcomes between the two groups. Until now, the common belief in the medical profession has been that kidney donations from cardiac-death donors were less likely to be successful than those of brain-death donors. These findings suggest that the outcomes between the two are actually the same.
As the researchers say, to increase chances of success, allocation policy for kidneys from cardiac-death donors should aim to reduce cold ischaemic time, avoid large age differences between donors and recipients, and avoid donating kidneys poorly matched for HLA to younger recipients as this could reduce the chances of success if they need another transplant.