Kidney transplant's survival edge over dialysis narrowed for older patients given higher-risk donor organs

For most people whose kidneys have failed, a transplant is thought to offer a longer life than staying on dialysis. That has been the working assumption of kidney medicine for a quarter of a century. But donor kidneys vary, recipients are getting older, and the assumption has never been tested in a randomized trial.

A study of more than 64,000 people on transplant waiting lists in five European countries or regions, published in The BMJ in September, has now put numbers on where the advantage holds. With kidneys from standard donors, it held at every age. With kidneys from older or less healthy donors, it shrank as recipients aged. For 75-year-olds given the highest-risk category of organ, the researchers could not tell transplant and dialysis apart on five-year survival.

Why kidney transplant versus dialysis is hard to study

When kidneys fail, the two main treatments are dialysis, which filters the blood artificially, and a transplant. The fair test would be to assign patients at random to one or the other. As an Austrian research team wrote in 2022, randomized treatment allocation to kidney replacement therapy is not feasible. Kidney replacement therapy is the collective term for dialysis and transplant.

So the evidence comes from registries, and registries mislead in a specific way. The landmark work was a longitudinal study of mortality in 228,552 patients who were receiving long-term dialysis in the United States, published in 1999. Longitudinal means that it followed people over time. It found that those who made it onto a waiting list were already different. In its authors’ words, healthier patients are placed on the waiting list for transplantation. Comparing transplant recipients with everyone on dialysis flatters the transplant.

That study instead compared transplant recipients with people still on the waiting list, and it found a pattern that has held ever since. In the first 2 weeks after transplantation, the risk of death was 2.8 times as high as that for patients on dialysis. Then the balance reversed. The long-term mortality rate was 48 to 82 percent lower among transplant recipients, depending on the subgroup.

A 2022 review in The BMJ showed how thin the evidence remained. The search identified 48 observational studies and no randomized trials. Most reported a long-term survival advantage for transplant, but 11 of those studies identified groups of patients in whom a transplant showed no clear advantage over staying on dialysis. The reviewers concluded that transplantation remains the better treatment for most patients, but some subgroups may lack a survival benefit.

How the study compared kidney transplant with dialysis

The new analysis, led by Rachel Hellemans, set out to quantify the survival benefit of deceased donor kidney transplantation versus continued dialysis according to who received the organ and what kind of organ it was.

It drew on European Renal Association Registry data from five countries or regions: Catalonia (Spain), Denmark, France, Norway, and the UK. Renal means relating to the kidneys. The patients were adults receiving dialysis and waitlisted for a first deceased donor kidney-only transplant between 2000 and 2019. A deceased donor is one whose organs are given after death. Of 64,036 such patients, 39,244 received a kidney.

The method is called target trial emulation. The target trial is the randomized trial one would ideally run. In the Austrian team’s phrase it is an idealized randomized clinical trial that is not feasible, and the emulation applies the rules of such a trial to records that already exist. Here that meant building a fresh comparison every month. Each month, patients who received a kidney were set against patients who were still waiting on dialysis at that point, and both were followed forward. What was compared was five year patient survival following deceased donor kidney transplantation versus continued dialysis.

The point of the design is to remove a head start. Classifying people as transplant recipients from the start of their treatment introduces immortal time bias, meaning that the transplant is credited with the time a patient had to survive in order to receive it.

Donor kidneys were sorted two ways. The first is by donor. Transplant medicine separates standard donors from those who meet the expanded criteria donor (ECD) definition. That means a donor aged 60 or over, or one aged 50 to 59 with at least two of three markers: a history of high blood pressure, a raised level of creatinine, which is a blood marker of kidney function, and death from a stroke. Kidneys from such donors do not last as long. One American analysis reported a 70% higher risk of graft failure compared with non-ECD transplants, that is, those from standard donors. Graft means the transplanted organ.

The second is by how the donor died. In donation after brain death, the heart is still beating when the organs are removed. In donation after circulatory death, it has stopped, and the organs spend a period without blood flow.

That gives four categories.

Donor category	Transplants	Share
Standard criteria, after brain death	16,897	43.1%
Standard criteria, after circulatory death	4,324	11.0%
Expanded criteria, after brain death	14,799	37.7%
Expanded criteria, after circulatory death	3,224	8.2%

Nearly half of all the transplants, then, used expanded criteria kidneys. The fourth category combines both disadvantages, and is the one called highest-risk in this article.

Where the survival edge held, and where it narrowed

Standard donor kidneys came out ahead across the board. Both kinds, after brain death and after circulatory death, showed higher estimated five year survival compared with continued dialysis regardless of recipient age.

Expanded criteria kidneys were a different story. The survival advantage linked to them decreased with increasing recipient age, albeit with greater statistical uncertainty among older patients. The fall was steepest for the fourth category, expanded criteria kidneys donated after circulatory death.

The paper gives its estimates for a patient of 75. Among 75-year-olds, estimated five-year survival after a transplant of that kind was 59%, with a plausible range of 51% to 66%. For 75-year-olds who stayed on dialysis it was 55%, with a range of 54% to 55%. The ranges overlap, and the authors treat the two as not distinguishable. The transplant estimate is much the looser of the two, a sign that few patients of that age received such kidneys. The same picture appeared irrespective of diabetes or cardiovascular disease status, that is, whether or not patients had diabetes or heart disease.

Two things stand out in those figures. The first is how serious kidney failure is at that age whatever is done. On dialysis, 45% of 75-year-olds were estimated to die within five years. With the highest-risk kidneys, the figure was 41%. The second is that the estimate still leans toward the transplant, by four percentage points. What the study shows is that the advantage in this group is small enough, and the group itself small enough, that it cannot be told apart from none.

The authors’ summary is measured. Standard criteria donor kidney transplantation was consistently associated with a survival benefit compared with continued dialysis. With expanded criteria donors, the oldest recipients had a smaller and more statistically uncertain estimated survival advantage over continued dialysis.

Early deaths after transplant in older patients

Part of the explanation lies in the first months. Patients of 75 who received an expanded criteria kidney after circulatory death were estimated to be more likely to die soon after the operation than their counterparts who stayed on dialysis. This group had a threefold higher early post-transplant mortality than those continuing dialysis.

That is the 1999 pattern again. A transplant puts its risk up front: a period of higher danger around the operation, repaid later by lower death rates. The older the recipient and the less durable the kidney, the less time there is to collect.

A study published in May in the American Journal of Kidney Diseases shows the same arithmetic in the United States. It applied the emulation method to adults aged 75 or over who were listed in the Organ Procurement and Transplantation Network registry between 2015 and 2023. Of 2,670 patients, 1,012 received a kidney.

In the first 90 days, the death rate among recipients was more than twice that of patients who stayed on dialysis. At 3 years, survival was equivalent between groups. By five years the transplant group had pulled ahead, with what the authors call a 111-day survival advantage, meaning that recipients lived an average of 111 days longer within those five years.

Those authors described the pattern plainly. In their summary, transplant recipients face a higher mortality risk in the first few months after surgery, but those who survive this early period live longer than patients continuing to receive dialysis. They wrote that their results support decisions made patient by patient and highlight dialysis as a reasonable alternative to a transplant at that age.

What earlier transplant and dialysis studies found

The new study is a sequel. In 2021 Hellemans and colleagues published a smaller analysis of adult Belgian patients waitlisted for a first deceased donor kidney transplant from 2000 to 2012, 3,808 in all. Among those aged 65 or over, mortality over the follow-up period was 16.3% with a standard donor kidney, 20.5% with an expanded criteria kidney and 24.6% with continued dialysis. Only the first of those was clearly different from dialysis.

The Belgian paper was candid about what it could not do. Its numbers were too small to allow a separate analysis according to transplantation from either a donor after brain death or one after circulatory death. Its authors wrote: “Older transplant candidates should be informed that any survival benefit with ECD transplantation may be small.” They called for bigger European studies. The new one, with about 17 times as many patients, is that study, and it points the same way.

Not every analysis finds that the benefit fades out with age. The Austrian team quoted earlier used the emulation method on 4,445 patients and reported that transplant was associated with increased survival time across all considered ages compared with continuing dialysis. Over 10 years, the estimated gain was 3.01 years at age 60 and 2.48 years at age 70, smaller with age but still clear. That analysis reported results by the age of the recipient, not by the category of donor kidney.

An older American study asked a slightly different question, and one closer to the choice patients face. Published in 2005 in JAMA, it included 109,127 patients receiving dialysis and added to the kidney waiting list. It compared accepting an expanded criteria kidney with the alternative of waiting, which could mean more dialysis or a standard kidney later.

Deaths around the operation meant that cumulative survival did not equal that of standard-therapy patients until 3.5 years posttransplantation. It took three and a half years, in other words, for the early deaths to be made up. After that the expanded criteria recipients did better, with a long-term risk of death 17% lower. The advantage was concentrated among patients over 40 and in regions where waits were long.

That points to something the headline comparison in the new study does not capture. A patient offered an expanded criteria kidney is rarely choosing between that kidney and dialysis forever. The realistic alternative is continued dialysis while waiting for a better donor offer, and how long that wait is likely to be varies from place to place.

What the comparison leaves out for older patients

It is not a trial. Emulation tightens the comparison but cannot make it random. Patients who received a kidney in a given month may have been fitter than those who did not, in ways a registry does not record.

Survival is not the only reason for a transplant. The study counted deaths. The American study of people aged 75 or over named the lack of data on quality of life as a limit of its own work, and the main outcome here was survival too. Life on dialysis and life with a working transplant are different, and that difference is not in these figures.

The estimates for older patients are loose. The 59% figure for 75-year-olds carries a range from 51% to 66%. A real survival advantage of several points and a real disadvantage would both fit.

Five years is a short window for some. Because the risk comes early and the gain late, a five-year window may understate the benefit for recipients who go on to live longer. For a 75-year-old it covers a large part of the time at stake.

Two decades of practice. The records run from 2000 to 2019. Transplant practice changed over that time, and the results average across it.

Scope. The study covers first transplants from deceased donors in people already on dialysis, in five European health systems. It does not cover kidneys from living donors or transplants done before dialysis begins.

Whether to accept a particular kidney depends on a patient’s age, their health and how long the wait for another might be, which is assessed by their doctor.

A deceased donor kidney transplant was linked to better five-year survival than dialysis at every age when the donor met standard criteria, in registry data on 64,036 European patients, while for 75-year-olds given the highest-risk kidneys the estimated survival of 59%, against 55% on dialysis, could not be told apart, in an observational study that did not measure quality of life.