LIVING-DONOR KIDNEY TRANSPLANTATION

Living-donor kidney transplantation is the “gold standard” treatment for many individuals with end-stage renal failure (p30).2 (See also Asderakis et al3 and Tarantino4.) The number of living-donor kidney transplants has increased considerably over recent years.i Superior graft and transplant recipient outcomes are well documented5 6 and have prompted new strategies promoting living-donor kidney transplantation. For instance, the UK’s Human Tissue Act 2004,ii implemented 1 September 2006, permits paired and pooled donation,iii and non-directed altruistic donation of kidneys.,iv In response to the growing number of patients who have end-stage renal disease and die while awaiting renal transplantation, some centers have expanded their pool of potential living donors by including potential donors over 60 years of age. There is evidence to suggest that donor outcome values in this age group are comparable with those for younger age groups and that age should no longer be considered a contraindication for donation by a living donor.7 8

RISK

The mortality risk of living-donor nephrectomy has been estimated at 0.03%.9 The consensus from published reports of follow-up studies is that living-donor nephrectomy can be done with little major morbidity.10 11 The recent introduction and expansion of laparoscopic technique has been driven by the shorter convalescence time that the technique makes possible for donors. Concerns have been expressed over the safety of the procedure. However, recently published data from the UK Transplant National Registry suggest that living donation has remained a safe procedure in the UK during the period of introduction of the laparoscopic procedure.12

The Council on Ethical and Judicial Affairs of the American Medical Association issued a report on the transplantation of organs from living donors that stated, “The risks to a kidney donor ... are fairly well understood, have a relatively low incidence, and are considered minimal beyond the regular risks of surgery”.13

In his article Underestimating the risk in living kidney donation,1 Walter Glannon suggests that the long-term risk in a living donor donating a kidney and the personal cost may be higher than previously thought. This risk, he says, may become more significant given the increasing incidence of diabetes in developed countries, where it is the most common cause of end-stage renal disease.

Swedish registry data show that 85% of over 400 kidney donors were alive after more than 20 years of follow-up. The expected survival rate was 66%. Survival was 29% better in the donor group.14 15 Fehrman-Ekholm and colleagues have reported upon the glomerular filtration rate and the prevalence of hypertension as compared with the expected values according to age and gender. In their series of over 400 donors, no accelerated loss of kidney function was observed in living donors who had normal renal function at the time of nephrectomy.15

Najarian et al studied living kidney donors 20 years or more after donation by comparing renal function, blood pressure and proteinuria in donors with siblings. They found that the perioperative mortality after living-donor nephrectomy was low. In long-term follow-up of their living donors, they found no evidence of progressive renal deterioration or other serious disorders.16

Notwithstanding the fact that living-donor kidney transplantation undoubtedly entails risk, these reports, along with others on long-term outcome, are encouraging17 v (see also Narkun-Burgess et al18 and Kasiske et al19). However, as Ommen and colleagues point out, there has been little critical analysis of existing studies of long-term medical outcomes in living donors.20 Their review analyses issues in study design that affect the quality of the evidence and summarises possible risk factors in living donors. They highlight that virtually all studies of long-term outcomes in donors are retrospective, many with large losses to follow-up, and therefore are subject to selection bias; most studies have small sample sizes and are underpowered to detect clinically meaningful differences between donors and comparison groups; and many studies compare donors with the general population, whereas donors are screened to be healthier than the general population and so this may not be a valid comparison group. The suggestion in their conclusion is that prospective registration of living kidney donors and prospective studies of diverse populations of donors are essential to protect living donors and preserve living-kidney donation.20 However, as I am sure Ommen and colleagues would agree, just as the absence of proof is not proof of absence; the absence of proof is not proof in itself.

While the transplant community are committed to saving lives through clinical transplantation and continuing to develop an understanding of transplant immunobiology, they are equally committed to protecting living donors. For instance, an International forum held in Amsterdam in 2004 resulted in the publication of a comprehensive report on the care of the living kidney donor.21 The UK guidelines on living-donor kidney transplantation place particular emphasis on evaluation of the potential donor (see http://www.cambridge-transplant.org.uk/program/renal/lrdgui.pdf). No doubt all transplant healthcare workers would give their support to well-designed research and collaborative prospective studies that might provide them with valuable outcome data that they can then pass on to prospective living donors.

UNDERSTANDING THE RISK:BENEFIT RATIO

In his paper, Glannon identifies three factors that he says justifies reassessment of the risk:benefit ratio in living-donor kidney transplants.1 The first of these is that “graft survival of organs from living donors in transplant recipients is not permanent—they may need a second transplant after 20 or 30 years.” In some transplant recipients, however, graft survival is permanent in the sense that they die with a functioning graft in situ. Many would consider a graft survival of 20 or 30 years a successful transplant and almost certainly a better outcome than survival statistics on dialysis would suggest. The 5-year survival of incident patients in the UK on dialysis is only 42.6%.vi

The second factor that Glannon highlights is that “immunosuppression to sustain the graft puts the recipient at risk of infection.” Renal transplant recipients are susceptible to infection,22 but treatment with immunosuppression (anti-rejection treatment) to prevent rejection of the graft is not peculiar to living-donor transplantation. Deceased-donor transplant recipients also receive immunosupression. Immunosuppression treatments have improved the outcome of these grafts so significantly over recent years23 vii that it would seem irresponsible to perform any transplant without it.,viii The point is unclear.

Finally, the third factor is that healthy living donors might subsequently develop diabetes and end-stage renal failure. If this occurred, says Glannon, then the loss in quality life years for a person who was healthy at the time of donation could be considerable. One would hope that adequate donor assessments would help to minimise the likelihood of this possibility, but a protocol that provides exhaustive exclusion of all possible harm to a potential living donor is very unlikely to be sustainable. A donor may, for instance, be knocked down by a bus. The increasing incidence and prevalence of diabetes in developed countries is surely a reason to give forethought to the ways in which morally acceptable systems might be put in place in order to deal with the impending increase in end-stage renal disease that may well be likely in this population, not a reason to prevent autonomous individuals from participating in living-donor kidney transplantation.

Data reported by Silveiro and colleagues suggested that a nephrectomy in a patient with type 2 diabetes might increase the progression of disease. Further, the prevalence of microalbuminuria is increased after nephrectomy.24 Individuals who are at risk of developing type 2 diabetes include those with a family history of the disease, a body mass index of >30 kg/m2, a history of gestational diabetes, and excessive alcohol use. The following guideline was developed at the international forum held in Amsterdam in 2004: individuals with a history of diabetes or fasting blood glucose ⩾7.0 mmol/l on at least two occasions (or 2 hour glucose with an oral glucose tolerance test of ⩾11.1 mmol/l) should not donate (see Delmonico,21 note 23).

Glannon’s paper raises ethical questions about what constitutes permissible risk in transplantation, whether the benefits of living donation clearly outweigh any costs to the donor, and the extent to which transplant surgeons and the medical community in general should promote living donation of kidneys for transplantation. What Glannon’s analysis fails to take into account are the wishes of the donor and the risks that they are entitled to take as free, autonomous agents. The motives for participating in living-donor kidney transplantation are likely to be many and varied.

Of course, a major concern in any living-donor transplantation is that it exposes an otherwise healthy individual to the risks of major surgery for the physical benefit of another individual. Justification therefore requires careful consideration. In the case of living-donor kidney transplantation, the risks of nephrectomy must be balanced against the better outcome for recipients of living-donor transplants. Donors should be informed about potential risks. But it is not clear that more data on long-term outcomes are needed in order to determine whether it is permissible for individual autonomous agents to expose themselves to this or, indeed, any risk. The question that Walter Glannon raises is one of the degree of risk individual living donors should be permitted to take in order to provide a body part for clinical transplantation. Really, this is a general question concerning the degree of legitimate paternalism in restricting the risks autonomous agents may freely run and how this might conflict with a clinician’s responsibility to “do no harm”.

Glannon’s suggestion is that “physicians have a greater duty of care to healthy individuals willing to donate a kidney because they have more to lose from donating than individuals in end-stage renal failure who do not receive a transplant from a living donor” (my emphasis).1 Does this mean that a physician’s duty of care is (or should be) always greater for individuals who have more to lose? I am not clear how we could ever adequately define “more to lose” in such a way that it takes into account every individual’s ideas about what is valuable to them in their life. It would seem bizarre to suppose, for instance, that a physician’s duty to a patient who is imminently dying is less than that to a patient seen in a routine follow-up clinic because the patient has less or more to lose. What matters is respect for a person’s individual wishes about how their life goes. Glannon cites an example from the literature of a male teenaged patient with end-stage renal failure who received a kidney from his mother, then in her early 40s. The recipient died a few years after the transplant. The mother, considered to be in perfect health with no known risk factors for renal disease, subsequently developed insulin-dependent diabetes. Her remaining kidney failed and she would have required dialysis and a place on the transplant list but died of a myocardial infarction.25 Was her decision to donate wrong? She may have enjoyed a wonderful few years with her son and considered her decision to donate one of her kidneys to her son the best decision she ever made. In much the same way, a 65-year-old man may decide to donate one of his kidneys to his ailing spouse so that they might spend a good quality of life together in retirement, enjoying holidays abroad together, for example. In this instance, the long-term outcome may be entirely irrelevant to both husband and wife.

Glannon asks the question: “At what point does the risk become medically and morally significant?”.1 Any medical risk associated with an operation is likely to be defined in terms of the likelihood of its occurring and the effect it may have on the individual if it were to occur. Whether a potential individual donor is prepared to take this risk is likely to vary. The “medically significant risk” that one individual donor is prepared to take is not necessarily always going to be the same as that which another might be prepared to take. Why should it? It is far from clear that the relationship between a medically significant risk (whatever it may be) and a morally significant risk is always linear, and it seems unlikely that a precise definition could accurately account for an individual donor’s wishes. Surely it makes more sense to talk of a risk that takes on moral significance for the individual concerned. The suggestion in Glannon’s argument is that if a medically significant risk exists and is morally significant, the donation should not take place and it is the responsibility of clinicians and healthcare workers to ensure this. But not allowing an individual donor to undertake a procedure that carries with it a medically significant risk that they are nonetheless prepared to take is morally significant, too. And it is difficult to see why Glannon’s argument, supported by little in the way of empiricism, should bring an end to living-donor kidney transplantation, particularly when it is widely accepted as being the gold standard treatment for end-stage renal disease.

Glannon’s argument is essentially a suggestion that despite the current acceptance of living-donor kidney transplantation as the gold standard treatment for end-stage renal disease, clinicians and healthcare workers should act paternalistically and not allow the transplant to go ahead, because of a combination of medically and morally significant risk and a lack of empirical evidence. The basis for this argument is a duty of care to, first, do no harm.

In this paper I have presented a review of empirical donor outcome data and made two suggestions. First, it is not clear that medical professionals have underestimated the risk associated with living-donor kidney transplantation. Second, nor is it clear that more data on long-term outcomes are needed in order to determine whether it is permissible for individual autonomous agents to expose themselves to this or, indeed, any risk.

Provided that the organ donation takes place in a clean and safe healthcare environment, that individual potential donors are adequately informed about the donation process and its associated risks on the basis of available evidence, that their decision to donate is voluntary (not coerced) and that they have the capacity to be able to come to a decision regarding donation, then, whatever their motivation, their decision to participate in living-donor kidney transplantation is legitimate. If these are the circumstances in which donation takes place, I would agree with Walter Glannon that there are at present no compelling grounds for arguing that living-donor kidney transplantation should be prohibited or become much more restricted.

CONCLUSIONS

Living-donor kidney transplantation is the gold standard treatment for many individuals with end-stage renal failure. The consensus from the empirical published evidence is that living-donor nephrectomy can be done with little major morbidity, and reports on long-term outcome of living donors are encouraging. It is not clear from the data available that medical professionals have underestimated the risk associated with living-donor kidney transplantation. Well-designed collaborative prospective studies on long-term donor outcome may provide valuable information for both potential living donors and potential living-donor transplant recipients. Supporting such research is logical and desirable.

The motives for participating in living-donor kidney transplantation are likely to be many and varied. Undoubtedly, living donors are exposed to risk. However, individual autonomous agents are entitled to take risks and their individual choice to participate in donation is legitimate. Restricting the risks that autonomous agents may freely run on the basis that this is legitimate paternalism because it might conflict with a clinician’s responsibility to “do no harm” is not compelling grounds for arguing that living kidney donation should be prohibited or become much more restricted.

The global shortage of organs available for transplantation ultimately means that every year thousands of individuals who value their life die needlessly. This is an unacceptable loss of human life. Saving life is one of the most wonderful things an individual can do for another. Promoting any strategy that will assist in saving life and preventing human suffering within acceptable moral limits is legitimate.