Can Old Be Too Old for Kidney Transplantation?

As an impressionable young medical student at McGill University in Montreal, I had the good fortune to attend the Grand Rounds in 1963 that highlighted Canada's first cadaver kidney transplant. A lot has happened in the world and in transplantation since then, including the fact that I am 44 years older and have spent at least 40 of the last years involved continually with transplantation. Those were good years to be in transplantation, watching and participating in a dream as it evolved into an everyday reality. As outcomes kept improving, both our attitudes toward what was achievable and the indications for transplant eligibility kept expanding. With increasing age and experience, our personal definitions of “old” and “elderly” kept changing as well, influencing our thoughts on whether age limits make sense in kidney transplantation. Clearly we were not alone. In the European Dialysis and Transplant Association–European Renal Association registry, the number of kidney transplants for patients older than 60 years of age increased from 2.9% in 1983 to 9.94% in 1992, whereas in 1999, 12.5% of all transplants were older than 65 years of age (1). Therefore, it is not surprising that many articles are being published today defining outcomes in ever-older patients, as we attempt to convert an increasing number of elderly dialysis patients into transplant recipients. In the current issue of this Journal, Rao et al. (2) describe, using information derived from the Scientific Registry of Renal Recipients, the experience in the United States with renal transplantation in patients older than 70 years of age. They reviewed the fate of 5667 elderly dialysis patients wait-listed during the 15-year period 1990–2004 inclusive. Of those, 2438 received a kidney transplant. Transplanted patients had a 41% less risk of death compared with wait-listed candidates. A lesser-but-definite mortality benefit extended to recipients of expanded criteria donors (ECDs) and also to patients with diabetes and hypertension as the cause of their renal failure. The mortality benefit wasn't immediate. The relative risk of death was greater for transplant recipients immediately after transplantation but, after 125 days, the relative risk was less than 1 and diminished progressively over the course of time. Similarly, the time to equal survival was between 1 and 2 years, but, by 4 years, the survival advantage for transplant recipients was 15 percentage points greater (66% vs. 51%). Granted, wait-list patients with more severe co-morbid problems were less likely to be transplanted, emphasizing the importance of patient selection in this more vulnerable population. And, as expected, recipients of living donor transplants fared the best in every category measured. To validate the merit of transplanting a potentially high-risk population like the elderly, we need to demonstrate that transplant outcomes in this population are not only better than what is observed in nontransplanted patients but also reasonably equivalent to outcomes of transplants in other more traditional patients. Rao et al. make a cogent case for renal transplantation in elderly patients older than 70 years of age by fulfilling the first criterion, at least in relation to survival. As a registry review, they were unable to deal with quality-of-life issues. However, the literature is already replete with quality-of-life studies, and virtually all demonstrate the benefits of transplantation compared to continued dialysis for all age groups. For the second criterion, we need to compare outcomes in elderly patients and younger patients, especially those in contiguous and moderately younger age groups for whom there is little dispute about transplantation. We don't want to “waste” kidneys, an already-scarce resource, on patients who will derive little benefit from them. Comparative analyses with younger age groups will always be influenced by the fact that younger people live longer than older people, emphasizing the need to examine both crude and death-censored data for graft survival. With few exceptions, the overwhelming majority of studies suggest both graft survival and adjusted patient survival is not strikingly different in older than in younger patients (1). It is possible therefore to make a good case for transplantation in the elderly, even those older than 70. At issue is how to do this in a constructive way that doesn't compromise the ability of younger patients to access the limited resource of available kidneys, that is, without so-called organ wasting. Some practices can influence this. First, careful patient selection for wait-listing is essential. Some flexibility is, of course, necessary. As an example, consensus guidelines established by the Canadian Society of Transplantation set no age limit for transplantation but suggest that candidates should have a reasonable probability of surviving beyond current waiting times for transplantation and emphasize periodic reassessment while on the wait list to assure newly developed contraindications are identified (3). Donor selection also is critical. Age matching appears to be the key. In the European Senior Program (ESP), where kidneys are allocated on an old-for-old basis, many kidneys are used that would otherwise be discarded (1). After the introduction of ESP in 1999, use of older recipients and donors increased from 2% to 16% and 11%, respectively. Delayed graft function and 1-year graft and patient survival were similar to conventionally matched recipients, despite significantly older donors and recipients (4). ECDs also are a potentially important source of kidneys for the elderly, with acceptable results as shown in the work of Rao et al. (2). With careful selection and proper informed consent, especially in relation to recipient longevity, older living donors are also a potential source of kidneys that may not be appropriate for much younger patients (5). Can we in fairness set an age limit on kidney transplantation? It seems not. Transplantation for both older and elderly patients, although not without significant risk, is better than staying on dialysis. And it can be achieved in many cases without “kidney wasting” by careful patient selection and wait list monitoring, by strategies using age matching of donor and recipient, by use of ECD kidneys, and by selected use of older living donors.

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